How to Safely Use LSD – How to Use Psychedelics

LSD is the most widely studied psychedelic, with hundreds of published research papers (see below). An LSD experience is similar in many ways to psilocybin mushrooms, but often individuals feel like they are better able to direct and control the experience.

LSD studies have shown success in treating depression, anxiety, smoking cessation, and many other psychological conditions. LSD consistently produces powerful long-term improvements in these conditions, even with just a single dose.

Before you begin, be sure to read our safety section and see the special safety considerations for LSD at the bottom of this page.

LSD is a powerful chemical and taking the correct dose is essential. Because LSD is active at very, very small quantities and because it is typically delivered on small pieces of paper, it is difficult to independently assess the dose (this issue is less of a problem with mushrooms or MDMA). Taking too much LSD can lead to feelings of dissociation and alienation.

Be sure that you know the dose that you are taking. A single dose or tab of LSD can vary widely in strength, so make sure you know the quantity in micrograms. A 100ug dose is a good starting point if you have never taken LSD before and should provide a calm and opening experience. If you are interested in deeper psychological work or spiritual exploration, and have a lot of experience at lower does, you may decide to move up to 400 or 500ug, but only do so if you are very comfortable with lower doses. Do not use LSD unless you are very confident of the quality and dose that you have. Its best to use a source that someone you know has also used and can vouch for.

LSD will typically be delivered on small pieces of paper that the LSD is diffused onto. It may also be provided in liquid or pill form, or even diffused into a sugar cube.

Typically, people feel very free and open in the days following an LSD experience. Remember that you need at least 12 hours before you try to sleep, so if you begin too late in the day, you may have some trouble falling asleep and could be a little tired the next day.

Most people find that they have an afterglow from their LSD experience that can last days or weeks, improving their mood and outlook and keeping them very open to others. Ideas and issues that you explored during the experience will have a new clarity too them. Emotionally difficult topics, memories, and experiences are likely to feel much safer and will bring up less fear when you remember them. You are likely to feel better able to tackle challenging emotional experiences in your life.

LSD has been shown in many research settings to dramatically reduce anxiety, depression, and other psychological challenges with just a single dose. However, you may wish to repeat the experience a few times to further explore and address any emotional and psychological issues that you are working with.

In addition to our standard safety guidelines, there are two particularly important precautions for LSD use:

Psychedelics have been misunderstood and misrepresented for decades. That's changing. Please help us share safe, responsible information on using psychedelics by sending this page to friends, and posting to Facebook, Twitter, and Google:


How to Safely Use LSD - How to Use Psychedelics

How to Treat Depression with Psychedelics

Many people find their day to day experience of life is filled with anxiety, limiting the activities they do and the enjoyment they have in life. Psychedelics like mushrooms and LSD have been used for decades to treat anxiety disorders and to reduce anxiety levels.

In some cases, these substances seem to directly alleviate feelings of anxiety, even at very small doses (below the level at which they subjectively alter consciousness). For other people, psychedelics help them explore the root causes of their anxieties and fears and find peace with them. And for many people, psychedelics bring them to a place a spiritual peace and openness that can become a new touchstone for letting go of anxiety or learning not to identify with it so strongly.

This description of the process may sound abstract to someone suffering from anxiety day to day, but like talking therapy, the healing process of psychedelics can be a little difficult to convey until youve tried it.

Recent clinical research has shown dramatic reductions in anxiety even after a single psychedelic experience with psilocybin mushrooms. Even for patients facing the extreme anxiety of terminal illness, psilocybin allows them to embrace their fate and find peace with their loved ones.

Heres one womans story of being treated with mushrooms as she was facing death, described in a New York Times article (see below):

Before Pam Sakuda died, she described her psilocybin experience on video: I felt this lump of emotions welling up . . . almost like an entity, Sakuda said, as she spoke straight into the camera. I started to cry. . . . Everything was concentrated and came welling up and then . . . it started to dissipate, and I started to look at it differently. . . . I began to realize that all of this negative fear and guilt was such a hindrance . . . to making the most of and enjoying the healthy time that Im having. Sakuda went on to explain that, under the influence of the psilocybin, she came to a very visceral understanding that there was a present, a now, and that it was hers to have.

Two weeks after Sakudas psilocybin session, Grob (the researcher) readministered the depression and anxiety assessments. Over all among his subjects, he found that their scores on the anxiety scale at one and three months after treatment demonstrated a sustained reduction in anxiety, the researchers wrote in The Archives of General Psychiatry. They also found that their subjects scores on the Beck Depression Inventory dropped significantly at the six-month follow-up.

Whats remarkable about the research results from this and many other studies is that even a single dose of a psychedelic substance can create long lasting changes, reducing anxiety, depression, and creating more emotional openness.

LSD, MDMA, and mushrooms have all been studied for anxiety reduction. Remember that a psychedelic experience can sometimes produce anxiety or can focus the mind on sources of anxiety, as part of the process of addressing the root causes. Starting with small doses and following all the safety guidelines can help reduce anxiety.

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How to Treat Depression with Psychedelics

Can You Take Psychedelics With Antidepressants?

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Moderate doses of psychedelics have been shown to effectively treatdepression,anxiety,PTSD, andother mental health conditions and even microdoses havebeen reported to hold significant benefit. Although we dont recommend it, many people are turning to psychedelics as a form of self-treatment for mental health conditions. And this brings up the potential problem of antidepressant medication interfering with the effects of psychedelics.

Unfortunately there has been no solid research performed on the interaction between psychedelics and antidepressants. Therefore most of the advice we provide here is based on anecdotal evidence and case reports. We recommend discussing issues with your physician before making any decisions.

The classic psychedelics (includingLSD,psilocybinandDMT) work by affecting the serotonin system, and most antidepressants work by targeting serotonin signaling too. Therefore wed expect for there to be some kind of interaction between the two unfortunately we just dont know anything for sure right now.

From anecdotal reports, it looks as if the SSRI class of antidepressants weakens the effects of classic psychedelics although this absolutely doesnt mean you should take more of the psychedelic substance to compensate.

Many people advise against taking Lithium or other tricyclics with classic psychedelics, as they have been known to put people intocomatose statesorinduce seizures.Avoid this combination until we know for sure about its safety!

MAOI medications appear to haveeffectssimilar to SSRIs when combined with classic psychedelics.

Since we know so little about how classic psychedelics and antidepressants interact, we advise against taking them together. Dont risk making things worse for yourself. If you are absolutely determined to try a psychedelic, it may be wise to wean yourself off your medication first but always check with your physician.

Anecdotal reportssuggest that takingMDMAwhile on antidepressants can either numb the effects, completely abolish the effects, or cause a really unpleasant hangover! Since SSRIs mess with your serotonin system, and bind to some of the same targets as MDMA, there is the potential for unpleasant interactions. Dr Ben Sessa, an MDMA researcher, saysThe general rule is dont combine SSRIs with MDMA.

Taking MDMA while on MAOIs is alsopotentially dangerous. Its definitely best to avoid this combination, as it could lead toserotonin syndrome(which can be fatal!).

We dont know much about what you can combine withmescaline, but as its mode of action is similar to the classic psychedelics, its probably best to assume that it wont combine well with antidepressants.

Ayahuascais a little more complicated than other psychedelics when it comes to antidepressants, because the psychedelic brew contains MAOIs, which can cause fatal reactions when mixed with other drugs. We advise a total purge from all substances before taking ayahuasca, to avoid the risk of the potentially fatalserotonin syndrome.

Here is a listof all substances you should absolutely avoid if youre determined to take ayahuasca.

Ibogaineis another natural psychedelic with a potential risk of toxicity. Healthcare professionalsrecommend weaning off all medicationbefore taking a dose of ibogaine.

Be aware that ibogaine ispotentially the most dangerous psychedelic substance out there, as it can cause heart failure in seemingly safe situations. It is usually a last resort for people suffering from severe addiction.

We know nothing about interactions here although we know thatSalviaworks on a very different neurotransmitter system than most antidepressants, and we havent heard any reports of unpleasant effects resulting from mixing Salvia with antidepressants.

Were not medical doctors, and we dont pretend to be. Unfortunately the research isnt in place for anyone to give solid advice about mixing psychedelics with antidepressants. So be safe, be cautious, and always check with your physician before changing your drug-taking habits.

Continue reading here:

Can You Take Psychedelics With Antidepressants?

Beginners Guide to Microdosing Psychedelics

This is a guest post by Mansal Denton. Heis unaffiliated with Pure Nootropics and his thoughts and experiences are his own. Pure Nootropics does not condone or encourage the use of illicit or illegal substances.


Psychedelics are a big part of my personal growth and success.

The experiences with psychedelics have:

And Im not the only one

Popular writer, Michael Pollan, described The Trip Treatment of psilocybin and the potential use for treating anxiety, addiction, and depression.

Famed author and personality, Tim Ferriss, has had numerous discussions about psychedelics, such as LSD, mushrooms, and even ayahuasca. It was Ultimate Fighting Championship (UFC) host and comedian, Joe Rogan, who got me interested in the subject.

But beyond using psychedelics as a mystical experience, there is a subset who are finding ways to use them for a different purpose.

Through microdosing of psychedelic drugs, many people are finding cognitive advantages to improve the execution of their work and achieve more.

Less than a month before writing this piece Rolling Stone published an article about how LSD microdosing became the hot new business trip Of course, Forbes, GQ, the Telegraph, and dozens of other outlets re-published the same popular piece (Nov 2015).

I have been saying that nootropics are used by Silicon Valley execs, Wall Street traders, and just about every other high performance individual in between, but this is the next level

Lets get started, shall we?

Austin, Texas is becoming a hub for a new kind of entrepreneur, hippie, and hipster breed. As gross as that might be to visually imagine, it actually creates an amazing environment for testing personal practices, such as microdosing.

While I have sifted through scientific research, particularly from Dr. James Fadiman in the 1970s, much of this is based on anecdotes, experiences, and interviews.

Names have been changed to protect those who shared their experiences.

Microdosing is using small doses of powerful psychedelic drugs in order to improve working conditions. In contrast, full psychedelic experiences are often mystical and not conducive to completing work-related tasks.

There are several purported advantages including:


Imagine you have been working on a problem for weeks without finding an adequate solution. You wake up every morning, put in your time, but still dont feel satisfied with your results.

That was the basis for a 1966 experiment organized by Dr. James Fadiman among others. This experiment took 27 male subjects (16 engineers, 2 mathematicians, 2 architects, 1 engineer-physicist, and others) and required them to bring a professional problem they had been working on for at least 3 months with a desire to solve it.

After providing these subjects with 200 mg of mescaline sulphate, the subjects had 4 hours to work on their professional problem. Almost all of them reported greater problem-solving ability and at least 12 had breakthrough solutions.


Eric Clough was an architect in 1966 during the same era of research who wrote The consensus among the architects interviewedseems to be that LSD, when administered under carefully controlled conditions, does enhance creativity aids in visualizing three-dimensionally, and generally heightens perceptivity. (Fadiman, 170)

Numerous microdosing practitioners report having more creativity, which often ties into problem-solving. However, for musicians and artists, the creativity may help produce exceptional work in the absence of a definitive problem that needs solving.


Many psychedelics drastically enhance mood and happiness because of their interaction with serotonin receptors. Psilocybin decreases depressive and anxiety-related symptoms. The same is true for most other psychedelic drugs through small microdoses.


In a book Tryptamine Palace, author James Oroc asserts Virtually all athletes who learn to use LSD believe that the use of these compounds improves both their stamina and their abilities. According to the combined reports of 40 years of use by the extreme sports underground, LSD can increase your re-flex time to lightning speed, improve your balance to the point of perfection, increase your concentration

It sounds nice, but I spoke with my friend Larry to get his experiences and confirmed the same phenomenon. Both LSD and o-acetylpsilocin (prodrug for psilocin) offered strong physical energy and endurance beyond the norm.

These are just a few of the benefits of microdosing specifically. Note that the heroic dose, which provides mystical and self-reflective experiences, does not provide the same problem-solving or physical endurance effects. In fact, it might be the opposite in some circumstances so be careful when microdosing.

In scientific studies, the letter n is used to refer to the sample size. If you test something in a group of 5 friends, the sample size is 5 (n=5). The term n=1 is used to describe a sample size of 1, which is you. Therefore, the popularized term in biohacking circles is meant to encourage self-testing as opposed to listening to what everyone else believes.

There are at least 3 acquaintances with whom I spoke about microdosing. Larry is an entrepreneur creating a health-food company and had the most extensive experiences with microdosing. He felt LSD had a more complete microdosing experience even though mushrooms improved his physical energy and endurance profoundly.

Both Larry and another named Josh reported cycling LSD microdoses once every 3 4 days because of tolerance and ability to connect with others. Larry concluded that 10 12 mcg is better for physical endurance and concentration, while 12 15 mcg is better for creative thinking and problem-solving.

In contrast to these generally positive experiences, there is a individual self-experiment by Gwern that showed No beneficial effects reachedLSD microdosing did not help me. He continues to show how he tested and calculated things.

Another trained pianist and composer on Reddit took 30 40 mcg microdoses and reported The experience could be described as slightly withdrawn and I felt like I had worse coordination and consequently lower accuracy in playing.

Given the mixed nature of these anecdotal experiences, I recommend taking an N=1 approach. Understand that each individual is different and the dosage and microdosing that works for one person may not work for you.

The evidence from Fadimans research in the 1960s along with other testimony leads me to be cautiously optimistic about microdosing benefits, but dont expect it to solve all your professional or personal problems.

Again, neither I nor Pure Nootropics condone or recommend using illegal or illicit drugs. This is the process for microdosing that is reported through the experiments of Dr. James Fadiman and the experiences of others.

Given that microdosing with LSD is most common. Here is a briefguide for most accurately dosing. This is called volumetric dosing and it offers the most superior and accurate result.

(Tools needed: Scale, Pipette bottle, distilled water, tab of LSD)

Here are some of the common mistakes people make when trying to microdose:

Mistake #1 Do not cut the tab of LSD into strips in order to divide the dosage. For one, this is incredibly difficult to do accurately (given the small size of most LSD tabs). It also does not account for hotspots, which are heightened concentrations and uneven distribution on the tab itself. Instead, use the volumetric dosing with distilled water method explained above.

Mistake #2 Taking the incorrect dose. While each dose will have different effects for different people, some guidance can be helpful. 20 mcg of LSD is usually considered the high end of the microdose range, but some people go as high as 50 mcg. For LSD the lower doses tend to have concentration and slight mood benefits (5 12 mcg) while 12 20 mcg is a dose for problem-solving and creativity with more felt effects.

If you are using o-acetylpsilocin for a mushroom microdose (easier than trying to weigh actual mushrooms precisely), dosage recommendations are around 3 4 mg for microdosing.

Mistake #3 Taking doses too often. Most accounts recommended once every 3 4 days maximum, but longer is also good. LSD is particularly subject to tolerance and doing it every other day can create uncomfortable relationships with reality.

Mistake #4 Obviously sourcing makes a big difference with microdosing. A poor quality product with a big dose is less impactful, but when you rely on a tiny dose to provide effects, opt for quality.

This is a guest post by Mansal Denton. Heis unaffiliated with Pure Nootropics and his thoughts and experiences are his own. Pure Nootropics does not condone or encourage the use of illicit or illegal substances.

If you have something youd like to add, wed love to hear from you, please comment below.

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Beginners Guide to Microdosing Psychedelics

Learn Everything You Need To Know About MDMA (Ecstasy)

(Ecstasy, E, X, XTC, Rolls, Beans, Adam, Molly)



Disclaimer: MDMA is a potentially illegal substance, and we do not encourage or condone the use of this substance where it is against the law. However, we accept that illegal drug use occurs, and believe that offering responsible harm reduction information is imperative to keeping people safe. For that reason, this guide is designed to ensure the safety of those who decide to use the substance.

Overview 01

MDMA, commonly known as ecstasy or Molly, is primarily a recreational drug that causes euphoric feelings, increased empathy with others, and enhanced sensations. Sounds and colors are often experienced more intensely, making MDMA a popular recreational drug at raves and music festivals.

Currently, it is in Phase III clinical trials for use as a therapeutic aid in the treatment of PTSD, and has been granted Breakthrough Therapy status by the FDA.

It is most commonly taken as an oral tablet that comes in a variety of shapes and colors, but it can also be snorted or smoked.

MDMA can be deadly when combined with other drugs (especially PMA/PMMA), and can also be deadly on its own at high doses.

History & Stats 02

The history of MDMA began decades before the rave culture that popularized it.

A common myth perpetuated by both the scientific community and media outlets is that MDMA was first synthesized and patented by the German pharmaceutical company Merck as an appetite suppressant.

Merck did synthesize the drug in 1912, but the appetite suppressant story is an urban legend. Instead, it was developed as a potentially life-saving blood clotting medicine.

Very little, if any, testing was done in the early years after its first synthesis. It wasnt until 1927 that Merck revived interest in the drug. A chemist named Max Oberlin predicted that MDMA might mimic adrenaline since the chemicals shared a similar molecular structure. Not long after these initial studies, however, the prices of chemical precursors skyrocketed and testing was put on hold.

It is not exactly known when the first human trials with MDMA were conducted, but the US military is known to have tested it and other drugs on humans in the 1950s.

The first recipe for MDMA was published in a polish-language scientific journal in 1960 and tablets began popping up in seized contraband in the 1970s.

Dr. Alexander Shulgin first read about MDMA in the early 1970s at which point he synthesized it and tried it himself, becoming the first person to officially record ecstasy use in a human subject in 1978.[1] In the 1980s, its use in MDMA-assisted psychotherapy was said to increase patient self-esteem and facilitate therapeutic communication.[2]

While Shulgin is often called the Godfather of Ecstasy, the real creator of MDMA was a German scientist named Anton Kollisch, who died in 1916 never knowing the legacy he left.

Since 1985, MDMA has been listed as a schedule I drug in the United States, making it effectively illegal for all uses, but some limited clinical trials have been approved and conducted in recent years. In 2011, a federal court sided with the ACLU who argued that punishments for MDMA possession and use were based on outdated science which led to overly severe prison sentences,[3] but other courts have upheld the previous sentencing laws.

The annual National Survey on Drug Use and Health found that MDMA had been used at least once by 13.1% of people between the ages of 18 and 25, and 6.5% of people age 26 and over. Full results from the survey are below.

These trends appear to be holding relatively steady:

Its appearance in published reports and literature reached a peak in the early- to mid- 2000s and has fallen quite a bit since then:

Google search interest over the past decade or so has slowly but steadily increased before plateauing the past few years:

If youre enjoying this guide, youll probably love the information in our detailed Microdosing Course.

Microdosing is the most exciting trend in the world today when it comes to unlocking creativity, focus, and self-expression. But a lot of people dont know where to start or get overwhelmed by trying to figure everything out themselves from broken resources around the internet.

Thats why we put together this detailed, step-by-step course. It explains everything you wanted to know about microdosing (and even answers the questions you didnt know to ask).

MDMA Street Names 03

As one of the most popular psychedelics and party drugs, MDMA has earned a varied assortment of street names. In fact, there may be more nicknames for MDMA than for any other substance besides weed.

Some of these refer to the compound generally, in whatever form, while others refer to set preparations. Ecstasy could fall into either category but it usually refers to tablets, or pills.[15] Its name was supposedly changed from Empathy early on to boost sales appeal.[16]

The marketing of ecstasy pills, complete with trusted logos and brand names,[17] has actually spawned a number of other enduring street names, including Doves. However, most ecstasy brand names, while popular in their own right, havent caught on as street names for pills in general. These include Mitsubishi, Little Rocket, and Dolphin (or Blue Dolphin).[18]Some other generic street names for pills include:

Molly, short for molecular,[19] refers to crystal (powder) MDMA.[15] In the UK, its also known as Mandy. Other names from around the world include:[20]

Pharmacology 04

MDMA affects the brain by increasing activity levels of three different neurotransmitters: dopamine, norepinephrine (noradrenaline), and serotonin.[4]

Increases in dopamine account for euphoric effects, as well as increased energy. Physiological effects while under the influence of ecstasy are caused by increases in norepinephrine/noradrenaline. These include increased heart rate and blood pressure.MDMA effects on the serotonin system cause characteristic changes in mood, appetite, sexual arousal, and sleep cycles. Spikes in serotonin after taking MDMA likely account for feelings of emotional closeness and empathy that are commonly reported by users.

Potentially fatal neurological complications can occur following MDMA ingestion, likely due to short-term hypertension and dehydration that is induced by the drug. Necrosis of liver and heart tissue has also been reported in individuals where death was associated with the use of amphetamine derivatives.[5]

Many fatal cases are due to abnormally high doses, prior health complications, a bad batch of MDMA, or a combination of all of these. Its also particularly difficult to tell exactly how much of role MDMA plays in adverse reactions in many cases because users are more likely to have used multiple drugs.[6] Like with any substance, it should be used in moderation, as heavy users tend to experience more complications than occasional users.[7]

Clinical studies with pure MDMA have been conducted on over 1100 individuals without the occurrence of severe adverse effects.[8]

Pure MDMA? 05

The purity of MDMA is notoriously variable, especially in tablet form. In the US, for instance, the average MDMA concentration in ecstasy tablets (or pills) is reported to be 30.13%.[21] But this includes samples as low as 0% and as high as 100%. Also, while the sample size varies (from 1 to 1000 pills), individual state averages can be double or half the national average.

Still, this is something of a recent improvement. In 2008, police seizures of the chemical precursor safrole meant that, for years, street MDMA concentration in ecstasy pills was very often zero.[22] Since then, the percentage of dud pills (tablets containing no MDMA) has been rapidly falling. Meanwhile, the percentage of ecstasy pills containing MDMA alone, without any adulterants, has been climbing. In 2009, 60.1% of ecstasy tablets worldwide contained no MDMA whatsoever, whereas just 8.7% contained MDMA alone. By 2018, the situation was reversed: 8.8% of ecstasy tablets contained no MDMA, while 54.8% contained MDMA alone.[23]

Part of this has to do with new manufacturing methods. Underground chemists now synthesize MDMA with a less heavily restricted precursor. But it also has to do with the darknet, where vendor ratings and competition naturally drive the quality up.[24]

In fact, far from the days of there being too little MDMA in pills, nowadays theres often too much. Super-strength ecstasy tablets have made headlines in recent years for killing unsuspecting users. Whereas the MDMA content in ecstasy pills is traditionally between 80 and 120mg, some have been found to contain upwards of 300mg.[25] A high-end dose like this can be dangerous enough in itself, let alone when youre not expecting it.

EcstasyData.org and Pill Reports are excellent resources for gauging the safety of specific pills.However, they should only be used as a guide. The safest way to use ecstasy pills is to start with just half a tablet and gauge how you feel over an hour.[26][27]

What about the purity of Molly (crystal MDMA)?

Despite what you may have been sold, even in crystal or powder form, pure MDMA is difficult to find on the street. However, street MDMA concentration has been climbing in recent years. In the UK, at least, it has apparently reached 83%.[28] Accounting for the molar mass of the hydrochloride (HCl) salt that most MDMA is made as, this is pretty much the maximum purity.[29]

MDMA in pure form, or free base MDMA, has by definition a purity of 100%.

Unfortunately, whatever form its in, your ecstasy is unlikely to be pure. In other words, theres probably something else in itand adulterants can sometimes be deadly.Using an MDMA test kit is a good precaution. These can show up the presence of, firstly, MDMA, and secondly, toxic adulterants by a color change you can check on a chart. However, chemical reagent tests like this cannot tell you the purity and theyre only indicative at best. They should, therefore, be used alongside other harm reduction practices.[30]

A caution on PMA/PMMA (aka Death)

The prohibition of MDMA in most countries (and especially the police seizures of safrole in 2008/2010 interrupting the supply of ecstasy) has led to the emergence of unknown alternatives. These substances, about which we know relatively little, tend to be far more dangerous than MDMA. And yet theyre legal by default in many jurisdictions.

Following the procedure for making MDMA with aniseed oil instead of safrole, for example, yields not ecstasy but the problematic substances para-Methoxyamphetamine (PMA) or para-Methoxy-N-methylamphetamine (PMMA).[37] Both have been implicated in the deaths of unsuspecting users from as early as 1993.[38] In December 2014/January 2015, for instance, at least three men died after taking the same pink Superman pills containing PMA.[36][37]

PMA/PMMA can be 10-20 times more potent than MDMA.[36][37] So users taking a safe dose of what they believe to be ecstasy could be massively overdosing on a far riskier substance. PMA/PMMA are also slower-acting, which means experienced ecstasy users are likely to re-dose too soon, taking even more of this harmful drug into their bodies.

The trouble is, PMA/PMMA are not analogs of MDMA. They have a different pharmacological action. Unlike ecstasy, they block certain enzymes (e.g. monoamine oxidase, or MAO) that offset the release of serotonin. And, as a result, they can lead to serotonin syndrome, which can be deadly.[37][38]

Reagent testing can help to identify the presence of PMA/PMMA; however, the presence of real MDMA could disguise the presence of PMA/PMMA as adulterants. Checking pills against user reports online, e.g. at EcstasyData.org and Pill Reports, is, therefore, a sensible precaution.

If youre enjoying this guide, youll probably love the information in our detailed Microdosing Course.

Microdosing is the most exciting trend in the world today when it comes to unlocking creativity, focus, and self-expression. But a lot of people dont know where to start or get overwhelmed by trying to figure everything out themselves from broken resources around the internet.

Thats why we put together this detailed, step-by-step course. It explains everything you wanted to know about microdosing (and even answers the questions you didnt know to ask).

Effects 06

Most tablets available for recreational use contain between 80 and 150 mg of MDMA.[9] At this dose level, the onset of effects occur approximately 20 to 60 minutes after taking the drug, and the characteristic effects (euphoria, increased empathy, increased energy, enhanced sensations) typically last for 3 to 5 hours.

The MDMA high is usually characterized by a relaxed, euphoric state, including emotional openness, empathy, reduction of negative thoughts, and a decrease in inhibitions. Sounds and colors can also appear more intense.

Some adverse physiological effects can occur after ingesting MDMA and include elevated blood pressure and heart rate, nausea, chills, sweating, tremor, jaw clenching, hyperreflexia, urinary urgency, muscle aches or tension, hot and cold flushes, nystagmus, and insomnia. At higher doses, these physiological changes can result in severe adverse reactions.

MDMA overdose can (and does) kill. A high dose of MDMA can be a contributing factor in deadly conditions such as hyperthermia, exhaustion or hyperhydration. Additionally, MDMA can trigger serotonin syndrome, a potentially deadly overloading of the bodys serotonin levels.

Many people report an unpleasant comedown after a night of heavy MDMA use, including feelings of depression and fatigue. In our microdosing course, MDMA expert Dr Ben Sessa explains how the typical MDMA comedown is due to overexertion, poor sleep, poor diet, and polydrug use. As such, the MDMA comedown can be countered by eating and sleeping well after taking MDMA, keeping hydrated if youre dancing, and avoiding taking any other substances (including alcohol). Additionally, supplement kits are available online, claiming to help prepare and repair your body.

Myths 07

Although one of the most famous ecstasy-related deaths was caused by overhydration, MDMA itself will not make you drink yourself to death. The victim in this infamous case thought that by drinking a large amount of water, they would counteract an unpleasant ecstasy experience. Unfortunately, MDMA also makes it harder for the body to process water, meaning she died from water retention.

This doesnt mean you should avoid drinking water on ecstasy. Taking a very high dose of ecstasy can cause an inability to regulate your hydration, so you should make sure youre drinking water regularly. This is especially if youre dancing or exerting yourself.

The main cause of ecstasy-related deaths is a lack of education. People dont know how to take the drug safely, and end up increasing their health risks. When used responsibly, it is a relatively safe drug.

Although MDMA is very popular for use in clubs due to its enhancement of music and dance, that doesnt mean its exclusively a clubbers drug. Many people take it in a spiritual or therapeutic context. It can be used for various forms of personal and relationship development, and clinical trials are using it to treat sufferers of post-traumatic stress disorder.

There is no evidence that moderate use of MDMA (less than 100mg every few weeks) can cause damage to your brain.

Frequent, high dose use can cause heart problems and memory problems. Additionally, its relatively easy to overdose on MDMA if its combined with other drugs, especially PMA/PMMA. MDMA overdose can be lethal.

So although sensible use is relatively safe, it can be harmful in large amounts.

Therapeutic Use 08

In 2017, MDMA was approved for use in Phase 3 clinical trials in the US to treat posttraumatic stress disorder (PTSD).[10] [11] This is one of the last phases of testing before a drug is legally approved for therapeutic use. The trials are being funded by MAPS.

MDMA-assisted therapy for PTSD involves only a few administrations of the drug alongside guided professional therapy. The drug used in these trials is pure, with dosages strictly controlled unlikely the typical use of recreational ecstasy.

Patients who have undergone this therapy typically have a particularly treatment-resistant form of PTSD (many of them are war veterans). They report that MDMA therapy helped them approach their past trauma with a greater sense of acceptance, warmth, and compassion for themselves, allowing them greater opportunity to cope and heal.

Read more about the use of MDMA in the treatment of PTSD here.

Preliminary results from a few studies suggest MDMA is also a promising treatment for social anxiety in individuals with autism.[12] In a clinical setting, it can be used to shift a patient with social anxiety towards openness and encourage introspection. Early results suggest this is accomplished with infrequent or even single doses, eliminating the need for frequent administration of the drug, thereby mitigating the possible adverse side effects and many of the costs associated with longer-term, more involved therapies.

This same mechanism appears to operate in treating patients with life-threatening illnesses who experience clinical anxiety as well.[13]

If youre enjoying this guide, youll probably love the information in our detailed Microdosing Course.

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Personal Growth 09

Opinions vary among spiritual leaders and guides, but MDMA is sometimes cited as a tool that can be used for spiritual growth. Some spiritual teachers laud its ability to induce feelings of oneness, interconnectedness, empathy, compassion, warmth and kindness towards others, and, importantly, a lack of self-consciousness. States such as these are often catalysts for spiritual epiphanies and further spiritual and personal development.

As one Benedictine monk put it:

MDMA always propels me into an intimate space in conversation. There is a special quality to this conversation. One feels a heaviness, a sense of the weight of the moment, of something profound, of the seriousness of life itself. It is a space that is inner, without masks, without pretense, utterly open and honest. It is not an erotic intimacy, but a philosophical and mystical intimacy. Does this make any sense? One has the consciousness that this is an inner communication rarely achieved in ordinary discourse. There really are no adequate words to express this state of awareness, only to say, that it is essential in my experience.

MDMA can be used in many different sets and settings to invoke spiritual development from sitting quietly and introspecting, to meditating in groups, to therapy. Even rolling at raves can have a spiritual quality if the user approaches it with the right intentions.

MDMA could also be a useful tool for building or repairing relationships. Alexander Shulgin, the Godfather of Ecstasy, has written frequently on its potential use as a therapy for couples. The emotional intimacy produced by ecstasy could be the key to understanding our relationships and perhaps finding the places that need work.

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Legality 10

MDMA is a Schedule I substance in the United States, which makes it illegal to manufacture, distribute or possess without a DEA license.[39] Scandalously, this scheduling also suggests that ecstasy has no therapeutic valuecontrary to the findings of MDMA clinical trials for PTSD. However, given the strength of this research, it seems very likely (if not inevitable) that medical MDMA will soon be available on prescription.[40]

In the UK its a Class A, which is basically the same as Schedule I: Buying, selling or making MDMA is illegal without a license.[41]

The same is true in the majority of countries, but some are more permissive in practice. In the Netherlands, for example, where MDMA is very much illegal, possession of small amounts is often ignored by the police.[39] Meanwhile, in Peru, its perfectly legal to possess up to 250mg (one quarter of a gram) of MDMA, so long as its the only drug on you.[39][42]

FAQ 11

MDMA stands for 3,4-Methylenedioxymethamphetamine. Also known as ecstasy, its one of the most popular psychedelics in the world. Its widely seen as more of a party drug than LSD, psilocybin mushrooms, and so on. But its currently re-emerging as a breakthrough psychotherapeutic aid.[31]Researchers are especially enthusiastic about the potential for MDMA in PTSD treatment.

It comes in two basic forms: Tablets (or pills) and crystals (or powder). MDMA pills are often called ecstasy while Molly is MDMA in powder form, or MDMA crystals.

Ecstasy is a type of amphetamine, a stimulant class of drugs that includes speed and methamphetamine. But MDMA is considerably more benign than each of these. As an amphetamine, its also part of the phenethylamine class of substances, like mescaline. Of course, the effects are again substantially different. Based on these, MDMA may be classed as an entactogen or euphoric empathogen.

Regardless of MDMA dosage, ecstasy is a stimulating drug. Most people report a physical and emotional euphoria, along with mild visual effects, such as color enhancement. Increased stamina (e.g. for dancing) is also common.

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Psychedelic drug – Wikipedia

"Psychedelics" redirects here. For other uses, see Psychedelic.

Psychedelics are a class of drug whose primary action is to trigger psychedelic experiences via serotonin receptor agonism,[2] causing thought and visual/auditory changes, and altered state of consciousness.[3] Major psychedelic drugs include mescaline, LSD, psilocybin, and DMT. Studies show that psychedelics are physiologically safe and do not lead to addiction.[4] Studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction.[5]

Differing with other psychoactive drugs, such as stimulants and opioids, psychedelics tend to qualitatively alter ordinary conscious experience. Whereas stimulants cause energized feelings and opioids produce a relaxed euphoric state, the psychedelic experience is often compared to non-ordinary forms of consciousness such as trance, meditation, yoga, religious ecstasy, dreaming and even near-death experiences. Most psychedelic drugs fall into one of the three families of chemical compounds: tryptamines, phenethylamines, or lysergamides. Although lysergamides are their own group they are a tryptamine.

Many psychedelic drugs are illegal worldwide under the UN conventions, occasionally excepting use in a religious or research context. Despite these controls, recreational use of psychedelics is common.[6][7]

The term psychedelic is derived from the Greek words (psyche, "soul, mind") and (delein, "to manifest"), hence "soul-manifesting", the implication being that psychedelics can access the soul and develop unused potentials of the human mind.[8] The word was coined in 1956 by British psychiatrist, Humphry Osmond, the spelling loathed by American ethnobotanist, Richard Schultes, but championed by the American psychologist, Timothy Leary.[9]

Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme (Greek "phaneroein-" visible + Greek "thymos" soul, thus "visible soul").[10] Recently, the term entheogenic has come into use to denote the use of psychedelic drugs in a religious/spiritual/mystical context.

Psychedelics have a long history of traditional use in medicine and religion, for their perceived ability to promote physical and mental healing. In this context, they are often known as entheogens. Native American practitioners using mescaline-containing cacti (most notably peyote, San Pedro, and Peruvian torch) have reported success against alcoholism, and Mazatec practitioners routinely use psilocybin mushrooms for divination and healing. Ayahuasca, which contains the potent psychedelic DMT, is used in Peru and other parts of South America for spiritual and physical healing as well as in religious festivals.

Classical or serotonergic psychedelics (agonists for the 5-HT2A serotonin receptors) include LSD (also known as "acid"), psilocin (the active constituent of psilocybin mushrooms, commonly known as "magic mushrooms" or "shrooms"), mescaline (the active constituent of peyote), and DMT (the active constituent of ayahuasca and an endogenous compound produced in the human body)[citation needed].

This class of psychedelics includes the classical hallucinogens, including the lysergamides like LSD and LSA, tryptamines like psilocybin and DMT, and phenethylamines like mescaline and 2C-B. Many of these psychedelics cause remarkably similar effects, despite their different chemical structure. However, many users report that the three families have subjectively different qualities in the "feel" of the experience, which are difficult to describe. At lower doses, these include sensory alterations, such as the warping of surfaces, shape suggestibility, and color variations. Users often report intense colors that they have not previously experienced, and repetitive geometric shapes are common. Higher doses often cause intense and fundamental alterations of sensory perception, such as synesthesia or the experience of additional spatial or temporal dimensions.[11] Some compounds, such as 2C-B, have extremely tight "dose curves", meaning the difference between a non-event and an overwhelming disconnection from reality can be very slight.[citation needed] There can be very substantial differences between the drugs, however. For instance, 5-MeO-DMT rarely produces the visual effects typical of other psychedelics and ibogaine (a 'complex tryptamine') is also an NMDA receptor antagonist and -opioid receptor agonist in addition to being an agonist for the 5-HT2A receptors, resulting in dissociative effects as well (see dissociatives below). Research published in journal Cell Reports states that psychedelic drugs promote neural plasticity in rats and flies.[12]

The empathogen-entactogens are phenethylamines of the MDxx class such as MDMA, MDEA, and MDA. Their effects are characterized by feelings of openness, euphoria, empathy, love, heightened self-awareness, and by mild audio and visual distortions (an overall enhancement of sensory experience is often reported). Their adoption by the rave subculture is probably due to the enhancement of the overall social and musical experience. MDA is atypical to this experience, often causing hallucinations and psychedelic effects in equal profundity to the chemicals in the 5-HT2A agonist category, but with substantially less mental involvement, and is both a serotonin releaser and 5-HT2A receptor agonist.

Certain dissociative drugs acting via NMDA antagonism are known to produce what some might consider psychedelic effects. The main differences between dissociative psychedelics and serotonergic hallucinogens are that the dissociatives cause more intense derealization and depersonalization.[13] For example, ketamine produces sensations of being disconnected from one's body and that the surrounding environment is unreal, as well as perceptual alterations seen with other psychedelics.[14]

Salvia divinorum is a dissociative that is sometimes classified as an atypical psychedelic. The active molecule in the plant, salvinorin A, is a kappa opioid receptor agonist, working on a part of the brain that deals with pain. Activation of this receptor is also linked to the dysphoria sometimes experienced by users of opioids either therapeutically or recreationally. An unusual feature of S. divinorum is its high potency (dosage is in the microgram range) and extremely disorienting effects, which often include "entity contact", complete loss of reality-perception and user's experiencing their consciousness as being housed in different objects e.g. a pane of glass or a pencil. Additionally, ibotenic acid and muscimol, the active constituents of Amanita muscaria, may be regarded as psychedelic, dissociative or deliriant.

Despite many psychedelic drugs being non-addictive[15] and there being no evidence to support long term harm on mental health,[16] many of these drugs have been declared illegal under the UN Convention on Psychotropic Substances of 1971. In addition, many countries have analogue acts that automatically forbid any drugs sharing similar chemical structures to common illicit substances regardless of whether they are harmful.

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Psychedelic drug - Wikipedia

Psychedelic art – Wikipedia

Psychedelic art is any art or visual displays inspired by psychedelic experiences and hallucinations known to follow the ingestion of psychoactive drugs such as LSD and psilocybin. The word "psychedelic" (coined by British psychologist Humphry Osmond) means "mind manifesting". By that definition, all artistic efforts to depict the inner world of the psyche may be considered "psychedelic". In common parlance "psychedelic art" refers above all to the art movement of the late 1960s counterculture. Psychedelic visual arts were a counterpart to psychedelic rock music. Concert posters, album covers, liquid light shows, liquid light art, murals, comic books, underground newspapers and more reflected not only the kaleidoscopically swirling colour patterns of LSD hallucinations, but also revolutionary political, social and spiritual sentiments inspired by insights derived from these psychedelic states of consciousness.

Psychedelic art is informed by the notion that altered states of consciousness produced by psychedelic drugs are a source of artistic inspiration. The psychedelic art movement is similar to the surrealist movement in that it prescribes a mechanism for obtaining inspiration. Whereas the mechanism for surrealism is the observance of dreams, a psychedelic artist turns to drug induced hallucinations. Both movements have strong ties to important developments in science. Whereas the surrealist was fascinated by Freud's theory of the unconscious, the psychedelic artist has been literally "turned on" by Albert Hofmann's discovery of LSD.

The early examples of "psychedelic art" are literary rather than visual, although there are some examples in the Surrealist art movement, such as Remedios Varo and Andr Masson. It should also be noted that these came from writers involved in the Surrealist movement. Antonin Artaud writes of his peyote experience in Voyage to the Land of the Tarahumara (1937). Henri Michaux wrote Misrable Miracle (1956), to describe his experiments with mescaline and also hashish.

Aldous Huxley's The Doors of Perception (1954) and Heaven and Hell (1956) remain definitive statements on the psychedelic experience.

Albert Hofmann and his colleagues at Sandoz Laboratories were convinced immediately after its discovery in 1943 of the power and promise of LSD. For two decades following its discovery LSD was marketed by Sandoz as an important drug for psychological and neurological research. Hofmann saw the drug's potential for poets and artists as well, and took great interest in the German writer Ernst Jnger's psychedelic experiments.

Early artistic experimentation with LSD was conducted in a clinical context by Los Angelesbased psychiatrist Oscar Janiger. Janiger asked a group of 50 different artists to each do a painting from life of a subject of the artist's choosing. They were subsequently asked to do the same painting while under the influence of LSD. The two paintings were compared by Janiger and also the artist. The artists almost unanimously reported LSD to be an enhancement to their creativity.

Ultimately it seems that psychedelics would be most warmly embraced by the American counterculture. Beatnik poets Allen Ginsberg and William S. Burroughs became fascinated by psychedelic drugs as early as the 1950s as evidenced by The Yage Letters (1963). The Beatniks recognized the role of psychedelics as sacred inebriants in Native American religious ritual, and also had an understanding of the philosophy of the surrealist and symbolist poets who called for a "complete disorientation of the senses" (to paraphrase Arthur Rimbaud). They knew that altered states of consciousness played a role in Eastern Mysticism. They were hip to psychedelics as psychiatric medicine. LSD was the perfect catalyst to electrify the eclectic mix of ideas assembled by the Beats into a cathartic, mass-distributed panacea for the soul of the succeeding generation.

Leading proponents of the 1960s psychedelic art movement were San Francisco poster artists such as: Rick Griffin, Victor Moscoso, Bonnie MacLean, Stanley Mouse & Alton Kelley, and Wes Wilson. Their psychedelic rock concert posters were inspired by Art Nouveau, Victoriana, Dada, and Pop Art. The "Fillmore Posters" were among the most notable of the time. Richly saturated colors in glaring contrast, elaborately ornate lettering, strongly symmetrical composition, collage elements, rubber-like distortions, and bizarre iconography are all hallmarks of the San Francisco psychedelic poster art style. The style flourished from about 1966 to 1972. Their work was immediately influential to vinyl record album cover art, and indeed all of the aforementioned artists also created album covers.

Although San Francisco remained the hub of psychedelic art into the early 1970s, the style also developed internationally: British artist Bridget Riley became famous for her op-art paintings of psychedelic patterns creating optical illusions. Mati Klarwein created psychedelic masterpieces for Miles Davis' Jazz-Rock fusion albums, and also for Carlos Santana Latin Rock. Pink Floyd worked extensively with London-based designers, Hipgnosis to create graphics to support the concepts in their albums. Willem de Ridder created cover art for Van Morrison. Los Angeles area artists such as John Van Hamersveld, Warren Dayton and Art Bevacqua and New York artists Peter Max and Milton Glaser all produced posters for concerts or social commentary (such as the anti-war movement) that were highly collected during this time. Life Magazine's cover and lead article for the September 1, 1967 issue at the height of the Summer of Love focused on the explosion of psychedelic art on posters and the artists as leaders in the hippie counterculture community.

Psychedelic light-shows were a new art-form developed for rock concerts. Using oil and dye in an emulsion that was set between large convex lenses upon overhead projectors the lightshow artists created bubbling liquid visuals that pulsed in rhythm to the music. This was mixed with slideshows and film loops to create an improvisational motion picture art form to give visual representation to the improvisational jams of the rock bands and create a completely "trippy" atmosphere for the audience. The Brotherhood of Light were responsible for many of the light-shows in San Francisco psychedelic rock concerts.

Out of the psychedelic counterculture also arose a new genre of comic books: underground comix. "Zap Comix" was among the original underground comics, and featured the work of Robert Crumb, S. Clay Wilson, Victor Moscoso, Rick Griffin, and Robert Williams among others. Underground Comix were ribald, intensely satirical, and seemed to pursue weirdness for the sake of weirdness. Gilbert Shelton created perhaps the most enduring of underground cartoon characters, "The Fabulous Furry Freak Brothers", whose drugged out exploits held a hilarious mirror up to the hippy lifestyle of the 1960s.

Psychedelic art was also applied to the LSD itself. LSD began to be put on blotter paper in the early 1970s and this gave rise to a specialized art form of decorating the blotter paper. Often the blotter paper was decorated with tiny insignia on each perforated square tab, but by the 1990s this had progressed to complete four color designs often involving an entire page of 900 or more tabs. Mark McCloud is a recognized authority on the history of LSD blotter art.

By the late 1960s, the commercial potential of psychedelic art had become hard to ignore. General Electric, for instance, promoted clocks with designs by New York artist Peter Max. A caption explains that each of Max's clocks "transposes time into multi-fantasy colors."[1] In this and many other corporate advertisements of the late 1960s featuring psychedelic themes, the psychedelic product was often kept at arm's length from the corporate image: while advertisements may have reflected the swirls and colors of an LSD trip, the black-and-white company logo maintained a healthy visual distance. Several companies, however, more explicitly associated themselves with psychedelica: CBS, Neiman Marcus, and NBC all featured thoroughly psychedelic advertisements between 1968 and 1969.[2] In 1968, Campbell's soup ran a poster promotion that promised to "Turn your wall souper-delic!"[3]

The early years of the 1970s saw advertisers using psychedelic art to sell a limitless array of consumer goods. Hair products, cars, cigarettes, and even pantyhose became colorful acts of pseudo-rebellion.[4] The Chelsea National Bank commissioned a psychedelic landscape by Peter Max, and neon green, pink, and blue monkeys inhabited advertisements for a zoo.[5] A fantasy land of colorful, swirling, psychedelic bubbles provided the perfect backdrop for a Clearasil ad.[6] As Brian Wells explains, "The psychedelic movement has, through the work of artists, designers, and writers, achieved an astonishing degree of cultural diffusion but, though a great deal of diffusion has taken place, so, too, has a great deal of dilution and distortion."[7] Even the term "psychedelic" itself underwent a semantic shift, and soon came to mean "anything in youth culture which is colorful, or unusual, or fashionable."[8] Puns using the concept of "tripping" abounded: as an advertisement for London Britches declared, their product was "great on trips!"[9] By the mid-1970s, the psychedelic art movement had been largely co-opted by mainstream commercial forces, incorporated into the very system of capitalism that the hippies had struggled so hard to change.

Examples of other psychedelic art material are tapestry, curtains and stickers,[10] clothing,[11] canvas and other printed artefacts[12] and furniture.[13]

Computer art has allowed for an even greater and more profuse expression of psychedelic vision. Fractal generating software gives an accurate depiction of psychedelic hallucinatory patterns, but even more importantly 2D and 3D graphics software allow for unparalleled freedom of image manipulation. Much of the graphics software seems to permit a direct translation of the psychedelic vision. The "digital revolution" was indeed heralded early on as the "New LSD" by none other than Timothy Leary.[14][15]

The rave movement of the 1990s was a psychedelic renaissance fueled by the advent of newly available digital technologies. The rave movement developed a new graphic art style partially influenced by 1960s psychedelic poster art, but also strongly influenced by graffiti art, and by 1970s advertising art, yet clearly defined by what digital art and computer graphics software and home computers had to offer at the time of creation. Conversely, the convolutional neural network DeepDream finds and enhance patterns in images purely via algorithmic pareidolia.

Concurrent to the rave movement, and in key respects integral to it, are the development of new mind-altering drugs, most notably, MDMA (Ecstasy). Ecstasy, like LSD, has had a tangible influence on culture and aesthetics, particularly the aesthetics of rave culture. But MDMA is (arguably) not a real psychedelic, but is described by psychologists as an entactogen. Development of new psychedelics such as 2C-B and related compounds (developed primarily by chemist Alexander Shulgin) are truly psychedelic, and these novel psychedelics are fertile ground for artistic exploration since many of the new psychedelics possess their own unique properties that will affect the artist's vision accordingly.

Even as fashions have changed, and art and culture movements have come and gone, certain artists have steadfastly devoted themselves to psychedelia. Well-known examples are Amanda Sage, Alex Grey, and Robert Venosa. These artists have developed unique and distinct styles that while containing elements that are "psychedelic", are clearly artistic expressions that transcend simple categorization. While it is not necessary to use psychedelics to arrive at such a stage of artistic development, serious psychedelic artists are demonstrating that there is tangible technique to obtaining visions, and that technique is the creative use of psychedelic drugs.

Bohemian wall hangings and Hippie Tapestries

Psychedelic and Trippy wallpapers collection

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Psychedelic art - Wikipedia

Psychedelic Drugs and the Serotonergic System

Most of us know someone who has taken antidepressants. But psychedelic drugs? Not so much. Many people believe they are illegitimate and dangerous. You might be surprised to hear that psychedelic drugs like MDMA and LSD have a lot in common with antidepressants. They both work with the same neurotransmitter in the brain: serotonin.

And indeed, antidepressants and psychedelic drugs promise to heal similar mental illnesses and can also have similar side effects. Do you know how they work in the brain? No? Good! Thats exactly what this article is about. Before we can talk about your brain on these drugs, though, its important to have a basic understanding of the brain and its serotonergic system. Dont worry, its super fascinating stuff, and easy as 1-2-3:

Below, well talk about neurotransmitters, synapses and chemical signaling. If these things are even vaguely familiar to you, then read on. If not, I recommend reading part 2 of Tim Urbans fantasticand highly entertainingNeuralink and the Brains Magical Future story on the Wait But Why blog. Youll learn everything from brain anatomy to neural networks in just 15 minutes.

When a neuron fires, the cell body (soma) sends an electrical signal down its axon to its axon terminals. This is where one neuron connects to the dendrites of the next neuron. In between is the synapse. From the axon terminals, a chemical signal activates the dendrites and sends a message to the soma of the next neuron. The soma collects the messages and once a threshold is exceeded, it fires off an electrical signal down its own axon and the process repeats.

Chemical signals are made from neurotransmitters. How they are produced, sent and received is the key to understanding the interactions between drugs and the serotonergic system.

You have probably heard of the neurotransmitters dopamine, serotonin, adrenaline and oxytocin. A simplistic view:We have more than 100 different types of neurotransmitters in our brain and their job is facilitating the communication between neurons. Think of a neurotransmitter as a language: some neurons speak dopamine, others speak serotonin, others speak adrenaline and so on. While some neurons are multilingual, lets say fluent in serotonin and dopamine, most of them speak just one language. All neurons which speak serotonin make up the serotonergic system.

The serotonergic system is amongst the oldest neurotransmitter systems in the brain. It might be as old as 750 million years; even single-celled organisms carry serotonin receptors. In humans, those neurons originate from the raphe nuclei in the brainstem and form a network spanning every corner of the brain and influencing nearly every aspect of our lives. It plays a key role in regulating mood, sexual behavior, aggression, impulsivity, cognitive function, appetite, pain, thermoregulation, circadian rhythm, sleep and memory.

Serotonergic pathways in the brainWith all of these control functions, it makes sense that many prescription drugsand most antidepressantstarget the serotonergic system. What might not be so obvious, however, is that psychedelic drugs like MDMA (aka. molly, ecstasy), LSD (aka. acid) and psilocybin (aka. magic mushrooms) also stimulate the serotonergic system to create their unique effects.

All those substances do essentially one thing: they raise the serotonergic activity in the brain. Why? Because raising serotonergic activity makes you happy, social and active; whereas lowering serotonergic activity makes you depressed, irritable and more prone to mental illnesses.

This is where it gets really interesting. Before we dive into the life of a serotonin molecule, lets make sure were all on the same page. Take another look at the more detailed version of how communication happens at the synapse. On the top is the axon terminal of the sender-neuron which is often referred to as the presynaptic neuron. On the bottom is the receiver-neuronthe postsynaptic neuron. The skin of the neurons is the membrane; and the little gap in between is called the synaptic cleft. What gets sent from the sender to the receiver? A chemical signal, otherwise known as neurotransmitter; and in the case of a serotonergic neuron the neurotransmitter is serotonin.

Now we get to the nitty gritty. The following graphic illustrates the lifecycle of a serotonin molecule. Follow the orange dots from one to seven and check out the explanation below.

Signaling in chemical synapses

Well over 90 percent of the serotonin in our body is made in our gut. But since serotonin cant cross the blood-brain barrier, it has to be synthesized in the brain from scratch. What does cross the blood-brain barrier however is tryptophan, the fundamental building block of serotonin. Within the neuron, enzymes turn tryptophan into 5-HT which is the chemical name for serotonin.

How does our body get tryptophan in the first place? Tryptophan is contained in certain foods, particularly proteins. You may have heard that turkey is rich in tryptophanso is every other kind of meat, as well as cheese, dairy products and eggs. Paradoxically, eating a protein rich diet is not necessary useful for a steady tryptophan supply in the brain. Why? Read my story about amino acid competition at the blood-brain barrier.

Serotonin is stored in tiny bubblesonly 50 nanometers in diametercalled vesicles. How does it get in there? Initially, the serotonin floats in the cytosol, the fluid within the neuron. A transport protein called VMAT2 fishes the serotonin out of the cytosol and channels it into one of the vesicles. The vesicles then travel closer towards the synaptic cleft and wait for their signal.

When signalled, the vesicles meld with the cell membrane in a process called exocytosis. The serotonin gets released into the synaptic cleft.

When serotonin binds to the receptors of the postsynaptic neuron, each receptor sends off a signal to the cell body of the neuron. When enough of these signals accumulate, the postsynaptic neuron fires, causing an electrical signal to travel down its axon to its own axon terminals, in turn causing a release of serotonin that stimulates the next neuron. This chain reaction cascades through any number of neurons.

Where does a serotonin molecule go after it has activated a receptor? There are a few options: (a) it may get taken back up into the presynaptic neuron; (b) it may get taken up by a neighboring glial cell (glial cells are the most abundant cells in the brainthey dont transmit signals but they do help keep everything neat and tidy); or (c) it may get diffused away from the synaptic cleft via extracellular fluid.

Along the presynaptic membrane are serotonin transporters (SERT) that pull serotonin back into the cell in a process called reuptake. These transporters are basically groups of proteins that act like a gate: one inone out. One molecule binds to the transporter on the outside of the membrane and changes the transporters configuration. Consequently, another molecule drops off, but on the inside of the membrane.

Back in the presynaptic neuron, some of the serotonin gets reloaded into vesicles and will be reused. Producing serotonin from scratch is a complex process and takes time. Therefore, recycling helps the brain maintain a steady supply.

Any remaining serotonin gets broken down by the enzyme MAO (monoamine oxidase) and excreted from the cell as the metabolite 5-HIAA (5-Hydroxyindoleacetic acid).

The brain cant produce large quantities of serotonin at once, therefore it doesnt release large quantities of serotonin at once either. In fact, serotonergic neurons have multiple ways of up- and downregulating their serotonin response in order to maintain balance and protect themselves from overstimulation.

Follow the orange dots below to see a few examples of these protection strategies.

If there is (1) a high concentration of serotonin outside the neuron, the neuron reacts with

Amazingly, a neuron can cause its receptors to retract behind the synaptic membrane, putting them out of reach of being activated by over-abundant serotonin. With fewer receptors available, fewer activations occur, and the neuron is in turn less likely to fire off a signal.

Receptors are not only found on the postsynaptic membrane. Some are located on the axon terminals or even directly on the soma of a neuron. If too much serotonin is floating around in the brain and these autoreceptors get activated, they send an inhibitory signal to the presynaptic neuron that causes it to (3) throttle the release of serotonin.

Do you recall from the beginning how serotonin regulates mood, sexual behavior, cognitive function, sleep, memory and so on? How does it accomplish all that? Well, in reality there isnt just one single type of serotonin receptorthere are 14. They are numbered from 1 to 7 and further categorized into A, B, C, etc. Remember, the chemical name for serotonin is 5-HT. Going forward well talk a lot about 5-HT2A receptors, since they are the target of hallucinogenic drugs like LSD and psilocybin.

All 5-HT subtypes possess special qualities in how they regulate mood, anxiety, impulsivity, aggression, migraines, etc. Some of these subtypes act as regular receptors at the postsynaptic membrane, while others act as autoreceptors on the axon terminals, dendrites or directly on the cell body. The 5-HT2A receptor, for example, is a receptor on the postsynaptic membrane and regulates mood, anxiety and schizophrenia. Wikipedia offers a fantastic overview of 5-HT receptor subtypes if you wish to go deeper.

Now that you know how serotonin acts in the synaptic cleft it will be easy for you to understand the mechanisms of antidepressants like SSRIs and MAOIs as well as psychedelic drugs like LSD, psilocybin and MDMA. Each of these substances stimulate serotonergic neurons, but each in different ways.

Before 1950 it was believed that mental illnesses like schizophrenia or autism were caused by refrigerator mothersmothers who were emotionally distanced and cold with their offspring. The psychiatric community had no idea that behaviour patterns, such as schizophrenic or autistic behaviour, might arise from neurochemical events in the brain.

In the late 1930s, serotonin was first discovered in the gut where it played a role in muscle contraction. It took another 15 years before it was detected in the brainwhich was in 1953but still only in the context of muscle contraction. One year later, in 1954 two scientists noticed the chemical similarity between serotonin and LSD.Chemical structure of LSD and serotonin

They had already known that LSD had peculiar effects on mind and behavior, because Sandoz Laboratories had marketed LSD as a psychiatric drug since 1947. Putting one and one together, these two scientists suggested that serotonin might play an important role in mental illness.

If neuroscience can be said to have a beginning, one could argue that it occurred in 1954, with the idea that the action of LSD might be related to its effects on the brain serotonin system.

After it became obvious, that serotonin was deeply involved in mental sanity it quickly became the center of attention of pharmaceutical companies. Understanding the mechanism by which mood is regulated allowed pharmacologists to experiment with ways to influence it. One result has been the creation of many antidepressant drugs. Here is how they work.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant drugs today. Youve probably heard of Prozac, Celexa, Lexapro, Seroxat or Zoloft. They are all SSRIs.

SSRIs bind to serotonin transporters (SERT) on the presynaptic membrane and block them. This means serotonin cant get taken back up into the presynaptic neuron. More serotonin remains in the synaptic cleft where it continues to bind to receptors and activates them.

Monoamine Oxidase Inhibitors (MAOI) are older antidepressants, which are still in use, but not commonly prescribed because of their potentially lethal effects. MAOIs keep serotonin from being metabolized and excreted from the neuron, which in turn increases its availability.

Antidepressants ultimately raise serotonin levels, so does MDMA.

MDMA is a sneaky bastard. Insidiously it takes control of the infrastructure and turns the whole system upside down. How does it do that? First, MDMA enters the neuron via the serotonin transporters (SERT). Once inside the neuron, it inhibits the vesicular transporters (VMAT2) which means that serotonin is not neatly packed within the vesicles anymore, but now accumulates within the cytosol. Then, MDMA reverses the direction of the SERT, meaning instead of transporting serotonin into the neuron, they now release it into the cleft and deny its reuptake. The result is a dramatic increase of serotonin levels in the synaptic cleft which makes the receptors on the postsynaptic membrane go haywire for a few hours.

Moreover, MDMA increases dopamine and norepinephrine (i.e. noradrenaline) levels, which gives it its ecstatic properties. This temporary overstimulation of the serotonergic system leaves the neurons depleted of serotonin and needing to recover after the drug use.

What if MDMA is taken daily to keep up colossal serotonin levels? The short answer is: doesnt work; the effect of MDMA is capped by the available serotonin. If the brain is depleted from serotonin, MDMA has no material to work with and therefore the effects would be rather disappointing for the user. The brain needs time to replenish its supply before the drug could achieve the desired effects once more. Many users feel irritable and depressed after using MDMA. But when using again is not an option, there isnt much of an addiction loop they could tap into. With this built-in mandatory refractory period, the physical addiction potential of psychedelic drugs is limited.

With a built-in, mandatory refractory period, the physical addiction potential of psychedelic drugs is quite limited.

Remember how the brain usually doesnt release large quantities of serotonin at once? Other neurotransmitter systems in the brain are more suitable for this task: dopamine for example. The dopaminergic system does react well to repeated stimulation and is therefore frequently involved in addiction. Drugs which target the dopaminergic system are cocaine, amphetamine, methamphetamine, but also Adderall and Ritalin.

Unlike MDMA, hallucinogens dont flood the brain with serotonin. They target a specific subtype of serotonin receptorthe 5-HT2A receptorto which they bind directly, thereby activating it. The 5-HT2A receptor is known to play a key role in regulating mood, anxiety, schizophrenia and consciousness.

There is so much to say about how hallucinogens affect the brain. The initial hypothesisthat hallucinogens increase the activity in certain areas of the brainwas recently abandoned. In fact, hallucinogens temporarily shut down some major connecting hubs.

Why does this stir a researchers blood? Because if you want to know what a certain area in the brain does, it helps to observe what goes missing if you shut it off. Turned out, shutting off those connector hubs led to the interruption of the brains default mode network (DMN). You can think of the DMN as something like a screensaver which randomly shuffles through images of your past, your future, your to-do list, the super size menu that you shouldnt have eaten, the sad face of a person you hurt and so on. Interrupting the DMN has very interesting consequences which we willat lengthcover in a future post. Its a phenomenally interesting topic that deserves its own post (and requires a couple of thousands more words to explain).

Also, when breaking up the regular communication pathways, the brain starts to communicate in brand new ways. This visualization shows brain regions communicating which one another in (a) a normal state or (b) after administering psilocybin. On the left you can see that the color-coded regions communicate mostly amongst themselves, i.e. the dots of the purple region talk to other dots within the purple region. But under the influence of an hallucinogenic drug the purple dots start talking to all kinds of other brain regions.

Communication pathways in the brain after (a) placebo and (b) psilocybin

These novel communication pathways might be able to explain the creativity-enhancing and problem-solving qualities that are often attributed to hallucinogenic drugs.

Whats the essential nature of science? (1) You find an interesting thing, (2) you test and observe how the thing behaves under different conditions and (3) you come up with a hypothesis.

Psychedelic drugs and the serotonergic system are deeply intertwined. Not only was LSD involved in the initial discovery of the serotonergic system which later revolutionized psychiatry. Today, psychedelic research could yet again revolutionize our understanding of the human brain. Manipulating 5-HT2A receptors has astounding effects on brain circuitries that are involved in the sense of self and consciousness. You can think of the 5-HT2A receptor as the little kids basket and hallucinogens as a potent tool to test it. Psychedelic drugs might be nothing less than our key to deciphering consciousness.

With brand-new imaging technology, we could now watch the brain as it loses its sense of time and space. We could observe which regions fall out of sync when it dissolves its sense of self. We could literally watch the brain as it changes its state of consciousness. The problem is, were not allowed to. The current drug legislation makes psychedelic research so difficult and so expensive, that only very few research teams manage to get approval and funding for their studies.

Criminalization of psychedelic drugs stands between science and the exploration of consciousness.

Having discovered the serotonergic system less than 70 years ago, there is much that remains unknown about this mighty and mysterious network of neurons. We know that it is crucial for a lot of processes, but the ins and outs are not well understood even today. It will be a long time before well figure out the exact mechanisms of this versatile system.

In the meantime, every new study on psychedelics reveals fascinating new insights about consciousness, the brains default mode network and mental disorders. Over the next posts in our Psychedelic Drugs series well cover the outcome of those recent studies.

Medical Benefits of Psychedelic DrugsPsychedelic Drugs and the Serotonergic System (Youve just read it)The Psychedelic ExperienceYour Brain on Psychedelic DrugsPsychedelics and Mental HealthMicrodosing LSD: Smart Drug or Placebo?MDMA-assisted Therapy

Wow, that was a lot of information to take in. But you did it! Now you know more about the serotonergic system than any of your friends (except if your friends are neuroscientists). Since you seem to be really interested in the topic you might want to get notified when we publish our next story.

If you are located in the Vienna area, we invite you to join the Psychedelic Society Vienna meetup, where well discuss the latest research and developments in the field.

Visit link:

Psychedelic Drugs and the Serotonergic System

How to Use MDMA (Molly) – How to Use Psychedelics

MDMA is a truly remarkable medicine for working with difficult emotional experiences. The clinical results have far exceeded other interventions for a range of uses (see the research section at the bottom of this page).

MDMA is a synthetic psychedelic, first developed by the pharmaceutical company Merck in 1912. It has been widely studied since then, particularly for psychotherapeutic uses. With the rate of academic research growing rapidly, it is likely that MDMA will become FDA approved for therapeutic use within the next few years, and MAPS.org is focused on moving it through the approval process. MDMA is being widely tested for post-traumatic stress, with results that surpass any other existing treatment method.

MDMA is a particularly appealing psychedelic for therapists and researchers because the subjective mental experience feels fairly stable, while creating a dramatic increase in emotional openness and a reduction in fear and anxiety.

Before you begin, be sure to read our safety section and see the special safety considerations for MDMA at the bottom of this page.

Because MDMA has anti-anxiety and anti-fear effects, it is generally considered safe to use a full dose your first time and each time you use MDMA (generally 75mg - 125mg depending on the individual). It is important to measure the dose carefully. Milligram-precision scales cost about 20 dollars (heres an Amazon search for milligram scale).

Some therapy protocols add a booster dose of about 60mg of MDMA 2-3 hours after the first dose to extend the period of therapeutic effects and provide more time for deep exploration.

MDMA will typically be in the form of a powder, pill, or crystal. Again, be sure that you are receiving pure MDMA, not mixed with other drugs or stimulants like caffeine. 'Molly' is another term for pure MDMA, distinguished from 'Ecstasy' which often contains MDMA but is not pure MDMA. If the MDMA is in pill form, youll have to be confident of the reported dosage, as fillers are added to create a pill and weighing the pill will not indicate the MDMA content. As always, do not take any MDMA if you are unsure of quantity or purity.

Once the MDMA has worn off, be sure that you drink lots of water and get a long peaceful sleep at night. MDMA can be mentally tiring and you need to rejuvenate.

Most people find that they have an afterglow from their MDMA experience that can last days or weeks, improving their mood and outlook and keeping them very open to others.

On the other hand, some people feel mentally drained by MDMA and have a foggy headed feeling for a day or two afterwards. Others will feel emotionally drained, and have a depressed mood for up to a week after the experience. Sometimes, these feelings begin two days after the experience, but not the day after. To combat this, some people who feel sensitive to that after-effect will take 5-HTP or L-Tryptophan (both are common supplements available from any source) for a few days after MDMA in an attempt to restore their serotonin levels. People who do feel drained after an MDMA session generally report that precise the MDMA dose can affect how they feel afterwards. Too much may leave them more drained than necessary. This is another reason to start with a modest, precisely measured dose to begin.

Nearly everyone, no matter how they feel the following week, finds that the thoughts, feelings, and emotional release that they experience on MDMA persists afterwards. In particular, any realizations that they had during the experiences tend to prove real and lasting.

Most remarkably, painful emotional associations with life experiences -- traumas, breakups, divorces, etc -- are dramatically reduced if that issue has been explored during the experience. You will find that when you think about that same painful experience after exploring it on MDMA, you will not have the same flood of emotional pain and tension that you would have had beforehand. The memory will be intact but the emotional strings will be looser.

Even for extreme emotional trauma, this holds true. In a recent research study for patients with PTSD, 83% of patients experienced reduced symptoms after just 3 MDMA sessions combined with therapy, vs. only 25% of patients who had therapy alone. Quite simple, MDMA is the most effective treatment for PTSD ever developed. Compare this level of success to traditional anti-depressants which have strong side effects and are dosed every day for years at a time (for a total of hundreds or thousands of doses) and which have very low rates of effectiveness, often just slightly above placebo.

In addition to our standard safety suggestions, there are three particularly important precautions for MDMA use:

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How to Use MDMA (Molly) - How to Use Psychedelics

How to Take Mushrooms (Psilocybin mushrooms / Shrooms …

Psychedelic mushrooms containing psilocybin are one of the oldest and safest traditional medicines and have been used for centuries in many countries around the world. The therapeutic and spiritual uses of mushrooms are what make it such an important tool for growth and healing.

Over 200 species of mushrooms containing psilocybin and psilocin are known, growing naturally in many parts of the world. Mushrooms are non-addictive and become less active with repeated short-term use. They do not have any overdose risk. Many experts consider them among the safest psychoactive compounds available (safer than tobacco, alcohol, and anti-depressants).

See the bottom of this page for recent academic studies on the therapeutic uses of mushrooms. From a recent article in the New York Times:

Before you begin, be sure to read our safety section and see the special safety considerations for mushrooms at the bottom of this page.

The strength of mushrooms can vary somewhat, because you are consuming the mushrooms themselves, not just the active agents. Different strains have different strengths and potency can somewhat decline over time.

It is not possible to overdose on mushrooms. However, taking a dose thats different than anticipated can cause temporary anxiety. Interestingly, this can happen if the dose is smaller than expected, as well as if it is larger. In fact, some therapists recommend starting with a fairly strong dose of mushrooms that will quickly move people past their own psychological frameworks and into a more spiritual state, thereby bypassing anxiousness. Other research has suggested that starting with a small initial dose and increasing in successive sessions reduces potential anxiety.

Mushrooms are non-addictive and become much less effective if taken repeatedly in a short period of time, as your body adjusts. This makes overuse less likely.

Typically, people feel very free and open in the days following a mushroom experience. You should try to get a good nights sleep afterwards, and you may feel a little tired the next day.

Most people find that they have an afterglow from their mushroom experience that can last days or weeks, improving their mood and outlook and keeping them very open to others. Ideas and issues that you explored during the experience will have a new clarity to them. Emotionally difficult topics, memories, and experiences are likely to feel much safer and will bring up less fear when you remember them. You are likely to feel better able to tackle challenging emotional experiences in your life.

The positive effects of mushrooms can last for years, even from just a single experience. In a recent study at Johns Hopkins Medical Center, an incredible 94% of participants who had a single dose of mushrooms said it was one of the top five most meaningful experiences of their lives. Another study found long lasting changes in openness more than a year after a single mushroom dose.

As you can read in the studies above and below, mushrooms have been shown in many research settings to dramatically reduce anxiety, depression, and other psychological challenges with just a single dose. However, you may wish to repeat the experience a few times to further explore and address any emotional and psychological issues that you are working with.

In addition to our standard safety suggestions, do not use mushrooms if you are currently taking psychoactive pharmaceuticals, such as anti-depressents, anti-anxiety drugs, etc. Always research any supplements or other medicines that you may be taking to avoid interactions.

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Tim Ferriss: depression, psychedelics, and emotional …

I couldnt think of a better guest to kick this thing off. Tim is not only one of my closest friends, but also is the one who most persistently encouraged me to launch a podcast.


In this episode, Tim talks both experientially and from his own deep dive into the literature of psychedelics and mental health. Tim is shifting his focus from investing in startups to funding experiments that he hopes will establish more reliable knowledge and therapeutic options for those suffering from anxiety, depression, and addiction.

If this topic even remotely interests you, I cant recommend Tims podcast with Michael Pollan, author of How to Change Your Mind, enough. (You should definitely read Pollans book as well.) Even if youve never had any exposure to psychedelics or their potential applications, I think youll find this subject matter really interesting, and I was very grateful for Tim to be so open and honest about his experiences.

Tim also shared his short list of acquired wisdom he returns to most reliably, which might be worth the price of admission alone.

What its like living in Austin. [01:00]

The differences between lifespan and healthspan. [08:00]

During childhood and adolescence, Tim believed he was not designed to be happy. [09:30]

Tims TED Talk and his close call with suicide. [11:15]

Why Tim wants to focus on discussing different facets of mental health on a first-hand basis. [15:15]

Whats the type of thinking that triggers Tims downward spirals? [17:15]

Why Tims changed his focus from investing in startups to investing in mental health. [18:00]

How self-talk can be your best friend or worst enemy. [20:00]

Why Tim thinks everyone, including Type A personalities, should try meditation. [23:00]

Why men, in general, are bad at dealing with depression. [31:00]

Peters (newly) most-gifted book, which is related to men and depression (I Dont Want To Talk About It by Terrence Real). (Peters previous #1 book: Mistakes Were Made [but not by me] by Carol Tavris and Elliot Aronson.) [32:45]

The benefits and drawbacks of self-talk. [35:00]

The need to treat ourselves as well as we treat others. Its womens version of the Golden Rule. Gloria Steinem [37:00]

How a couple of Tims podcasts (The Psychedelic Explorers Guide Risks, Micro-Dosing, Ibogaine, and More and Are Psychedelic Drugs the Next Medical Breakthrough? made Peter aware of the effectiveness of plants to treat patients. [38:30]

Peters first experience with psilocybin. [40:30]

What started Tims interest in psychedelics? [41:30]

Tims transformative experience with ayahuasca. [48:45]

How Tims experience and research led him to focus on furthering the science of psychedelics and mental health. [53:00]

How do you explain the ineffability of psychedelic experiences? [57:00]

What is ego dissolution, and how do you explain it? [1:00:00]

What are some of the meditation modalities, and meditation apps out there? Why can meditation be so hard to do, but worthwhile to stick with? [1:13:00]

Tim notes, The consistent program that you follow is better than the perfect program that you quit. [1:26:30]

Why has Tim made a big commitment (more than $1 million) to funding scientific research, and to psilocybin and MDMA research, in particular? [1:31:00]

The story of Katharine McCormick and the birth control pill, and what a small number of committed people can do to change the course of history. [1:34:30]

Why the FDA granted MDMA-assisted psychotherapy breakthrough therapy designation (which could expedite approval) for the treatment of PTSD, and how a Phase 3 clinical trial is in motion. [1:43:43]

Ibogaine and the treatment of opiate addiction. [1:48:30]

What is the Default Mode Network (DMN), how does it relate to mental health, and how do psychedelic compounds affect the DMN? [1:49:30]

Image credit: Homological scaffolds of brain functional networks (Petri et al., 2014)

Heres Michael Pollan explaining the DMN, and the side-by-side images in figure above, in How To Change Your MindIn a 2014 paper published in the Journal of the Royal Society Interface, the Imperial College team demonstrated how the usual lines of communications within the brain are radically reorganized when the default mode network goes off-line and the tide of entropy is allowed to rise. Using a scanning technique called magnetoencephalography, which maps electrical activity in the brain, the authors produced a map of the brains internal communications during normal waking consciousness and after an injection of psilocybin (shown [above]). In its normal state, shown on the left, the brains various networks (here depicted lining the circle, each represented by a different color) talk mostly to themselves, with a relatively few heavily trafficked pathways among them.

But when the brain operates under the influence of psilocybin, as shown on the right, thousands of new connections form, linking far-flung brain regions that during normal waking consciousness dont exchange much information. In effect, traffic is rerouted from a relatively small number of interstate highways onto myriad smaller roads linking a great many more destinations. The brain appears to become less specialized and more globally interconnected, with considerably more intercourse, or cross talk, among its various neighborhoods.

How MDMA, in the right setting, may help us clean up a very messy experience that did a lot of damage, Tim says. To help people to heal themselves in nonverbal ways. This is really key. Its very hard for people to talk their way out of something that they didnt talk their way into. [1:53:30]

Why has ibogaine gained the least traction in the US for treatment of opiate addiction? [2:00:00]

Tims first-hand experience with opiate addiction and overdoses. [2:06:30]

Unhappiness may be the single most important problem plaguing our civilization, and there are compounds that may be part of the solution. Is progress being made in terms of pushing through research and application? [2:13:30]

What does it take to reschedule a drug? [2:16:30]

The non-addictive potential of psychedelics. Food vs cocaine vs psilocybin. [2:18:00]

How Solve for Happy by Mo Gawdat has jumped into the #2 spot for most-gifted books from Peter. [2:23:50]

Peters most gifted or recommended books:

Tims most gifted or recommended books:

Was there anything not in Pollans book that Tim would have added? [2:25:00]

How Peter is very proud to be one of the Biggest Tools and where people can find Egg Boxing. [2:31:00]

From all the habits and tools that Tim has learned, what are the 3-5 things that he returns to most reliably? [2:33:00]

What advice would Tim give to his 20- or 30-year-old self? [2:36:00]

Tim Ferriss has been listed as one of Fast Companys Most Innovative Business People and one of Fortunes 40 under 40. He is an early-stage technology investor/advisor (Uber, Facebook, Shopify, Duolingo, Alibaba, and 50+ others) and the author of five #1 New York Times and Wall Street Journal bestsellers, including The 4-Hour Workweek and Tools of Titans: The Tactics, Routines, and Habits of Billionaires, Icons, and World-Class Performers. The Observer and other media have called Tim the Oprah of audio due to the influence of The Tim Ferriss Show podcast, which is the first business/interview podcast to exceed 200 million downloads.

Tim on Facebook: Tim Ferriss

Tim on Instagram: @timferriss

Tim on Twitter: @tferriss

Tims website: tim.blog

Tims podcast: tim.blog/podcast

Originally posted here:

Tim Ferriss: depression, psychedelics, and emotional ...

Psychedelics – Pharmacological Reviews

I. Introduction

I was delighted when the editors invited me to write a review on psychedelics, perhaps a watershed moment, representing a shift in opinion that has been developing for more than 3 decades with respect to research and understanding of psychedelics. When I began my graduate studies in 1969, it was politically correct in scientific circles to refer to these substances only as psychotomimetics, a negative term suggesting that they fostered a mental state resembling psychosis (Hoffer, 1967). Later, as it was realized that these compounds did not provide very realistic models of psychosis or mental illness, it became more correct to refer to them as hallucinogens, again a pejorative term suggesting that they principally produce hallucinations. Yet that is not what they do in most users at ordinary doses, so this term likewise is not particularly descriptive or useful, although it is still widely used and seems to remain the preferred name for these substances in most scientific writing. In addition, the term hallucinogen is often used as a rather broad category to include all kinds of psychoactive molecules, including cannabinoids, ecstasy, dissociative agents, and others.

This review will focus exclusively on the so-called classic serotonergic hallucinogens (psychedelics), which are substances that exert their effects primarily by an agonist (or partial agonist) action on brain serotonin 5-hydroxytryptamine (5-HT) 2A receptors, as discussed later. The discussion will not consider cannabinoids, dissociatives such as ketamine, salvinorin A (a specific opioid agonist), or entactogens such as 3,4-methylenedioxymethamphetamine (MDMA). In certain contexts, all of these and some related agents have been swept into the catchall category hallucinogens. Although they all can produce profound changes in consciousness, they have a different mechanism of action and will not be discussed unless there is a specific reason to do so.

The name psychedelics for these substances was coined by Humphrey Osmond in 1957, connoting that they have a mind-manifesting capability, revealing useful or beneficial properties of the mind (Osmond, 1957). This name has been popular among the lay public for more than 5 decades, but it has generally been frowned upon by the scientific community because it implies that these substances have useful properties. The notion that psychedelics can have beneficial effects has thus far not been embraced in most medical or scientific circles; indeed, federal funding agencies (e.g., the National Institutes of Health National Institute on Drug Abuse and the National Institute of Mental Health) have no mission to support research on potentially useful properties of psychedelics. Yet this term has remained popular with the public and even appears to be gaining popularity. As I intend to show in this discussion, however, the idea that psychedelics may have useful properties is not at all farfetched, and very recent clinical studies have reinforced the belief by many that psychedelics are well worth studying from a number of different perspectives. Indeed, one of the most striking developments in this field has been the initiation and successful completion of a variety of clinical studies of psychedelics in the past 15 years, most of which have been targeted to specific medical indications. As will be discussed later, the results have been, in the main, remarkably positive.

It should be kept in mind that the relative dearth of research on psychedelics in the past half century did not result from a lack of scientific interest, but rather occurred as a consequence of political forces that manifested principally in the United States in the 1960s and 1970s (Grinspoon and Bakalar, 1979). Use of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD) and marijuana by so-called hippies who demonstrated against the Vietnam War during the 1960s created great consternation among authorities and legislative bodies, both at the federal and state levels. Antiwar attitudes and rejection of conventional social norms by adolescents and college students were often perceived by the mainstream culture to be a consequence of drug use; hence, these substances were often believed to be perverting the minds of our youth. Furthermore, the outspoken Harvard University professor and firebrand Timothy Leary encouraged young people to turn on, tune in, and drop out, essentially coaching them to take drugs, discover their true selves, and abandon convention. Such messages did not play well with the mainstream culture, all while the mass media fanned the flames of public hysteria with greatly exaggerated reports of drug-induced insanity, chromosomal damage, attempts to fly, and so forth.

Strict laws were quickly passed. After the passage of the Controlled Substances Act of 1970, LSD and other psychedelics known at the time were placed into the most restrictive category of drugs, Schedule 1. This classification made them virtually impossible to study clinically and effectively ended any significant research into the pharmacology and medical value of psychedelics for more than 3 decades. Nevertheless, there can be no doubt that psychedelics played a substantial role in defining the youth culture of the 1960s and 1970s, with books and essays too numerous to cite being written on this topic. It is believed that more than 30 million people have used LSD, psilocybin, or mescaline (Krebs and Johansen, 2013). One suspects that had LSD never been discovered, the world might look very different today than it does now, for better or worse, depending on ones perspective.

Despite the recreational use of psychedelics, a quote from a book by Grinspoon and Bakalar (1979 Pg 192) needs to be kept in mind:Many people remember vaguely that LSD and other psychedelic drugs were once used experimentally in psychiatry, but few realize how much and how long they were used. This was not a quickly rejected and forgotten fad. Between 1950 and the mid-1960s there were more than a thousand clinical papers discussing 40,000 patients, several dozen books, and six international conferences on psychedelic drug therapy. It aroused the interest of many psychiatrists who were in no sense cultural rebels or especially radical in their attitudes.

One very important scientific consequence of the discovery of LSD also is often overlooked. The powerful psychologic effect of LSD was accidently discovered in 1943 (Hofmann, 1979a), followed only a decade later in 1953 by the detection of serotonin in the mammalian brain (Twarog and Page, 1953). The presence of the tryptamine moiety within LSD was also quickly seen to be the scaffold for the chemical structure of serotonin (Fig. 1).

Chemical structures of serotonin and LSD.

This recognition led to a proposal only 1 year later by Woolley and Shaw (1954) that mental disturbances caused by lysergic acid diethylamide were to be attributed to an interference with the action of serotonin in the brain. Therefore, one could reasonably argue that the whole field of serotonin neuroscience, and especially the role of serotonin in brain function, was catalyzed by the discovery of LSD! By way of illustration, in 1952, there were only 10 publications in the National Library of Medicine concerning serotonin, nearly all of them dealing with some aspect of its ability to constrict blood vessels. Only 8 years later, in 1960, there were 300 publications on serotonin, 35 of which were now focused on studies of serotonin in the brain. For comparison, in 1960, there were only 197 publications about norepinephrine (NE)/noradrenaline, a neurotransmitter that had been discovered and studied in the mid-1940s. Green (2008) provides an interesting overview of the 19501970 period of intense research activity after the discovery of serotonin in the brain.

There have been numerous recent reviews on this topic, usually titled as hallucinogens, and the reader is encouraged to consult these works for further details (Nichols, 2004; Nichols and Chemel, 2006; Fantegrossi et al., 2008a; Green, 2008; Passie et al., 2008; Winter, 2009; Griffiths and Grob, 2010; Vollenweider and Kometer, 2010; Brandt and Passie, 2012; Beck and Bonnet, 2013; Halberstadt and Geyer, 2013b; Baumeister et al., 2014; Halberstadt, 2014; Tyl et al., 2014). I wrote a comprehensive review on the subject in 2004, so the literature considered for this review will focus primarily, but not exclusively, on the years from 2004 to the present.

Psychedelics are a class of drug that cannot be fully understood without reference to a number of other fields of research, including anthropology, ethnopharmacology, psychiatry, psychology, sociology, and others. This review will focus mostly on pharmacology, both preclinical and clinical, but on occasion reference will be made to aspects of some of those other areas.

Psychedelics may be the oldest class of psychopharmacological agents known to man. Important examples of these substances include a substance used in ancient India known as Soma, which was highly revered and is frequently mentioned in the Rigveda, with numerous Vedic hymns written in praise of Soma (Wasson and Ingalls, 1971). In the ancient village of Eleusis, outside Athens, for more than 2000 years there was an annual all-night secret ceremony that is believed to have involved ingestion of a hallucinogenic brew known as (Wasson et al., 1978). We know almost nothing about the ceremony other than that profound insights about life could be achieved, and it was apparently a treasured once-in-a-lifetime opportunity for any Greek citizen who had not been convicted of murder.

Psilocybin mushrooms were used by the Aztec shaman in healing and in a variety of religious and divinatory rituals. These mushrooms were known as teonanacatl, meaning gods flesh (Ott and Bigwood, 1978; Schultes and Hofmann, 1979). The use of various psychoactive plant materials and substances was common in pre-Columbian Mesoamerican societies, including the Olmec, Zapotec, Maya, and Aztec cultures (Carod-Artal, 2015). In the Bradshaw rock art in the Kimberly region of Australia and in the Sandawe rock art in the Kolo region of Eastern Tanzania, one finds uniquely shared images such as the mushroom head symbol of psilocybin use, suggesting that the two cultures were linked and had shamanic practices that used psychoactive mushrooms (Pettigrew, 2011).

Peyote (Lophophora williamsii) is a small cactus native to the American Southwest and Northern Mexico that has been used for millennia and is consumed as a sacrament during services of the Native American Church. Two peyote samples from a cave on the Rio Grande River in Texas were analyzed and subjected to radiocarbon dating. The average age of the samples, both of which contained mescaline, dated to 37803660 BCE (El-Seedi et al., 2005). This evidence supports the use of peyote by Native North Americans as long ago as 5700 years (Bruhn et al., 2002). Classic psychedelics that have been extensively studied include LSD, shown earlier, mescaline, psilocybin, and N,N-dimethyltryptamine (DMT) (Fig. 2).

Chemical structures of classic psychadelics mescaline, psilocybin, and DMT.

Ayahuasca, also known as yag or hoasca, has a long history of use by natives in the Amazon valley of South America (Dobkin de Rios, 1971; Schultes and Hofmann, 1979). Ayahuasca is a decoction prepared from an admixture of two plants: the pounded bark from Banisteriopsis caapi vines and leaves from Psychotria viridis. The latter contains the hallucinogen DMT, a Schedule 1 controlled substance under U.S. law, and it is generally considered that the psychoactive effects of ayahuasca can be attributed to its DMT content. Although DMT is not orally active, B. caapi contains -carboline alkaloids that inhibit the liver monoamine oxidase (MAO) that normally breaks down DMT; thus, ayahuasca is taken orally as a tea. Its use has been incorporated as a sacrament into the religious practices of two syncretic Brazilian churches [Unio do Vegetal (UDV) and the Santo Daime] that have branches in the United States, with the U.S. Supreme Court rendering a 2006 decision to allow the use of ayahuasca by the UDV under the Religious Freedom Restoration Act.

In view of the widespread historical use of psychedelics as sacraments in a variety of other cultures, Jaffes (1990) definition for the class of psychedelics can perhaps be appreciated: the feature that distinguishes the psychedelic agents from other classes of drug is their capacity reliably to induce states of altered perception, thought, and feeling that are not experienced otherwise except in dreams or at times of religious exaltation. All pharmacologists will recognize that this definition for a class of psychoactive drugs is indeed quite unique!

One of the pioneers of LSD research, the late Daniel X. Freedman, noted that one basic dimension of behavior compellingly revealed in LSD states is portentousness the capacity of the mind to see more than it can tell, to experience more than it can explicate, to believe in and be impressed with more than it can rationally justify, to experience boundlessness and boundaryless events, from the banal to the profound (Freedman, 1968). Freedmans observation is completely consistent with Jaffes definition.

The use of psychedelics as a central feature of many religious practices, as well as the profound and unique psychopharmacological effects suggested by Jaffes definition and the observations of Freedman, surely makes us aware that psychedelics are an exceptional category of mind-altering substances. Indeed, this knowledge prompted Ruck et al. (1979) to coin the word entheogen as a replacement for the terms hallucinogen and psychedelic, both of which they felt had negative connotations. Entheogen is derived from the Greek roots entheos, meaning God (theos) within, and genesthe, meaning to generate. The word entheogen thus essentially refers to a substance or material that generates God or the divine within someone. Although the term entheogen is now seeing fairly wide acceptance within the culture of those who use these substances recreationally, a search of the term in the National Library of Medicine finds only five hits. Although it seems unlikely that the term entheogen will be adopted within the formal scientific community, the reader should realize that in some circles entheogen is generally synonymous with psychedelic. Nonetheless, it should be appreciated that the effects produced by psychedelics are highly dependent on the set (mental expectation) of the user and the setting (environment). A set and setting designed to facilitate a mystical experience will increase the probability of such an occurrence, whereas an unstructured or party-type setting is less likely to lead to a positive outcome.

Studerus et al. (2012) investigated the importance of 24 predictor variables on the acute response to psilocybin and confirmed that nonpharmacological factors play an important role in the effects of psilocybin. Variables examined included age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose. Their analysis was based on pooled data from 23 controlled experimental studies involving 261 healthy volunteers who had participated in 409 psilocybin administrations over a 19-year period in the authors laboratory. Multiple linear mixed-effects models were fitted for each of 15 response variables. Drug dose was shown to be the most important predictor for all measured response variables, but several nonpharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychologic problems in past weeks were most strongly associated with pleasant and mystical-type experiences. High emotional excitability, young age, and an experimental setting involving positron emission tomography (PET) most strongly predicted unpleasant and/or anxious reactions to psilocybin. Interestingly, in addition to confirming that nonpharmacological variables play an important role in the effects of psilocybin, an experimental setting involving PET most strongly predicted unpleasant and/or anxious reactions to psilocybin.

Two instruments have been most widely used to assess the subjective effects of hallucinogenic drugs. The first of these, the Hallucinogen Rating Scale (HRS) was developed by Strassman et al. (1994) during their studies of the intravenous administration of DMT. The HRS was first drafted based on interviews with 19 experienced DMT users and was modified during the early stages of their study. The final version, used for their double-blind study, contained 126 individual items. HRS items were placed into six conceptually coherent clusters: somaesthesia (interoceptive, visceral, and cutaneous/tactile effects), affect (emotional/affective responses), perception (visual, auditory, gustatory, and olfactory experiences), cognition (alteration in thought processes or content), volition (a change in capacity to interact willfully with themselves, the environment, or certain aspects of the experience), and intensity (strength of the various aspects of the experience). Subjects were asked to recall their experiences from the immediately preceding session. Most questions were scored on a 04 scale (0, not at all; 1, slightly; 2, moderately; 3, quite a bit; and 4, extremely).

The second assessment instrument widely used to quantify the subjective effects of hallucinogens is the Abnormal Mental States (APZ) questionnaire, first developed by Dittrich (1994, 1998) to measure altered states of consciousness (ASCs). In a series of 11 experiments using different induction methods in 393 healthy subjects, the hypothesis was tested that ASCs have major dimensions in common, irrespective of their mode of induction. The original version contained 158 items covering a range of phenomena potentially occurring during an ASC. The common denominator of ASCs was described by three primary oblique dimensions, designated as oceanic boundlessness (OSE, later as OBN), dread of ego dissolution (AIA, and later as DED), and visionary restructuralization (VUS, later as VRS). The APZ questionnaire became the international validated standard for the assessment of ASCs and the name was further revised to the OAV scales (Bodmer et al., 1994) and later to the five-dimensional altered states of consciousness (5D-ASC) (Dittrich et al., 2006). Details of the development of the original APZ questionnaire and its further refinements were summarized by Studerus et al. (2010). To overcome a variety of methodological limitations, Studerus et al. (2010) carried out a psychometric evaluation of the OAV and 5D-ASC in a relatively large sample from 43 pooled experimental studies of healthy subjects who had received psilocybin, ketamine, or MDMA. The total sample was composed of 591 drug sessions. After comprehensive and detailed statistical analyses, the authors found that the original OAV scales were multidimensional constructs, and arrived at an improved final model that had 11 factors: experience of unity, spiritual experience, blissful state, insightfulness, disembodiment, impaired control and cognition, anxiety, complex imagery, elementary imagery, audio-visual synesthesia, and changed meaning of percepts. Correlations between the 11 factors and their association with the original OAV scales were presented. The new lower-order scales were proposed to be better suited to assess drug-induced ASCs.

Mechanistically, psychedelics have agonist or partial agonist activity at brain serotonin 5-HT2A receptors. This molecular characterization will be elaborated in some detail later in this review, and aspects of the anatomic and functional importance of this receptor type will also be extensively explored. Discussions over the years with many colleagues working in the pharmaceutical industry have informed me that if upon screening a potential new drug is found to have serotonin 5-HT2A agonist activity, it nearly always signals the end to any further development of that molecule.

A recent study by Turton et al. (2014) reported on the subjective experience of intravenous psilocybin administered during a functional magnetic resonance imaging (fMRI) examination. Fifteen volunteers were administered an intravenous infusion of either placebo or 2 mg psilocybin and were blinded as to whether they would receive placebo or drug for a particular experiment. Drug infusion began 6 minutes after the start of a scan in a magnetic resonance imaging scanner. Subjects completed a visual analog scale rating the intensity of the drug experience at the start of the scan and prior to drug infusion, 5 minutes postinfusion, and 12 minutes postinfusion. All subjects subsequently were interviewed about the drug effects, and interviews were analyzed using interpretative phenomenological analysis, a qualitative method. All subjects reported that the onset of drug effect was very rapid and intense, with a duration of effect lasting 1015 minutes. The investigators identified nine broad categories of phenomenology. Altered somatosensory, visual, auditory, and proprioceptive sensations were reported, with 14 of 15 subjects describing perceptual changes as the primary effect of the drug. Thirteen subjects reported changes in perception of time, either speeding up or slowing down. The report describes a variety of effects on cognition, mood, memory, and spiritual or mystical experiences. Overall, subjects found the experience difficult to describe, yet most found it pleasant and positive.

In a new study by Schmid et al. (2015), LSD (200 g) was administered orally to 16 healthy subjects in a double-blind, randomized, placebo-controlled, crossover study. LSD produced a pronounced alteration in waking consciousness that lasted for 12 hours and included visual hallucinations, audio-visual synesthesia, and positively experienced derealization and depersonalization phenomena. Compared with placebo, LSD increased subjective well-being, happiness, closeness to others, openness, and trust. Increases in blood pressure, heart rate, body temperature, pupil size, plasma cortisol, prolactin, oxytocin, and epinephrine also were measured. On the 5D-ASC scale, LSD produced higher scores than did psilocybin or DMT. The authors also described subjective effects on mood that were similar to those reported for MDMA that might be useful in psychotherapy. No severe acute adverse effects were observed and the effects subsided completely within 72 hours.

In a very recent study by Carhart-Harris et al. (2015a), LSD was shown to enhance responsiveness to suggestion. Their study was prompted by very early reports indicating that LSD increased suggestibility (Sjobergand Hollister, 1965; Middlefell, 1967). Thus, Carhart-Harris et al. (2015a) administered LSD (4080 g, i.v.) to 10 healthy volunteers in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale and a mental imagery test. The two instruments were administered between 110 and 140 minutes after drug infusion, at the peak of the drug effect. Subjects scored significantly higher on the Creative Imagination Scale, but not the mental imagery test after LSD administration, compared with placebo. The magnitude of suggestibility enhancement was positively correlated with the subjects baseline trait conscientiousness. This enhanced suggestibility may have implications for the use of LSD as an adjunct to psychotherapy, but it also indicates that individuals with a high trait conscientiousness are particularly sensitive to the suggestibility-enhancement effect of LSD.

It has been axiomatic among users of psychedelics that music takes on an intensified and more enjoyable quality under the effects of LSD or other psychedelics, yet no modern placebo-controlled study had ever been carried out to confirm that widely held belief. Early studies at the Maryland Psychiatric Research Center found that music was a very effective stimulus and complement to the effect of LSD (Bonny and Pahnke, 1972). Gaston and Eagle (1970) also reported that the presence of music was much preferable to its absence in alcoholic patients undergoing treatment using LSD therapy, both by patient preference and treatment results. Numerous other studies had been reported on the value of music in the context of various shamanic and therapeutic approaches (see references in Kaelen et al., 2015). Very recently, therefore, Kaelen et al. (2015) tested the hypothesis that the emotional response to music is enhanced by LSD. Ten participants were administered placebo or various doses of LSD, including 40, 50, 70, or 80 g, infused intravenously over 3 minutes. They then listened to five different instrumental music tracks on each of two study days: a placebo day followed by an LSD day, separated by 57 days. Music tracks were chosen that produced the highest liking and lowest familiarity by a separate sample of nine participants. The question How emotionally affected were you by the music? was asked immediately after each track and served as the studys primary outcome. The nine-category Geneva Emotional Music Scale (Zentner et al., 2008) was also used. Mean scores for all music stimuli in response to the question how emotionally affected were you by the music? were significantly higher for the LSD condition than for placebo. In addition, all nine factors on the Geneva Emotional Music Scale were scored higher after LSD administration than after placebo. Emotions related to transcendence also were enhanced by LSD. Specific emotions showing the strongest enhancement included wonder, transcendence, tenderness, and power. Furthermore, there was a significant positive relationship between ratings of the intensity of the LSD effect and emotional arousal to music. The results of Zentner et al. (2008) support the hypothesis that LSD enhances music-evoked emotion.

The experimental study of mystical or ecstatic states engendered by psychedelics perhaps began with the so-called Good Friday experiment, carried out at Boston Universitys Marsh Chapel in 1962 by Walter Pahnke as his research for the Ph.D. in religion and society at the Harvard Divinity School. Pahnke (1963) examined the similarities and differences between experiences described by mystics and those induced by psilocybin. On Good Friday in 1962, 20 Christian theological student volunteers attended a 2.5-hour religious service in Boston Universitys Marsh Chapel. The setting and preparation of the subjects was designed to optimize a spiritual or mystical experience. In a double-blind procedure, subjects were given either an oral dose of 30 mg psilocybin, or a 200-mg placebo dose of nicotinic acid, administered in identical capsules. Based on responses to a variety of instruments and questionnaires, subjects who received psilocybin had experiences that were indistinguishable from those experienced by mystics. The experiences were powerful and personally meaningful. Doblin (1991) reported a follow-up to the Pahnke study in 1989 and was able to locate and interview 19 of the original 20 experimental participants. All of the psilocybin subjects felt that the experience had significantly affected their lives in a positive way and they expressed appreciation for having participated in the experiment.

An extension of the Good Friday experiment was recently carried out by Griffiths et al. (2006). The investigators used rigorous double-blind clinical methods to evaluate acute and longer-term effects of psilocybin (30 mg/70 kg) compared with an active comparator compound (40 mg/70 kg methylphenidate). A complex design was used to obscure which treatments were administered from the study participants and the monitors, and the study was designed to minimize adverse effects. Thirty-six healthy volunteers were enrolled, all of whom indicated some participation in regular religious or spiritual activities. Instruments used to assess effects 7 hours after drug administration were the HRS, the Addiction Research Center Inventory, the States of Consciousness questionnaire, and the Mysticism Scale. Seven to 8 weeks after each session, and before any additional session, subjects completed the Persisting Effects Questionnaire, the Mysticism ScaleLifetime, the Spiritual Transcendence Scale, the NEO Personality Inventory, and the Positive and Negative Affect Schedule Expanded Form. Based on measures of mystical experience, 22 of the 36 volunteers had a complete mystical experience after psilocybin administration, whereas only 4 did after the methylphenidate (placebo) sessions. Based on ratings of personal meaningfulness and spiritual experience, 67% of the volunteers rated the psilocybin experience to be either the single most meaningful experience of their lives or among the top five most meaningful experiences in their lives. Based on community observer ratings, psilocybin sessions were associated with significant positive changes in the volunteers behavior and attitudes.

Thus, when psilocybin was administered under structured conditions to well prepared volunteers, it occasioned experiences that had marked similarities to classic mystical experiences, imparting to the participants substantial personal meaning and spiritual significance. The investigators point out that the high value some subjects placed on the psilocybin experience may in part explain the long-term historical use of psychedelics within some cultures for divinatory or religious purposes. Griffiths et al. (2006) conclude with the statement that, The ability to prospectively occasion mystical experiences should permit rigorous scientific investigations about their causes and consequences.

Griffiths et al. (2008) subsequently conducted a 14-month follow-up of the subjects from their earlier study. Subjects were asked to identify in which session they experienced the most pronounced changes in your ordinary mental process. It was found that the 14-month retrospective follow-up ratings for the psilocybin session did not differ significantly from the immediate postsession ratings. Compared with methylphenidate, the psilocybin experience produced significant increases in ratings of positive attitudes, mood, social effects, and behavior at 14 months of follow-up. At the 14-month follow-up, 58% of the 36 volunteers still rated the psilocybin experience as among the five most personally meaningful experiences of their lives and 67% rated it as among the five most spiritually significant experiences of their lives.

A second study using a similar protocol with 18 volunteers examined dose effects of psilocybin, using 0, 5, 10, 20, and 30 mg/70 kg (Griffiths et al., 2011). The percentage of subjects who met the criteria for having a complete mystical-type experience increased with dose. Overall, 72.2% of volunteers had complete mystical experiences at either or both doses of 20 and 30 mg/70 kg. Positive ratings about life, attitudes about self, mood, social effects, and behavior also increased as a function of dose. Ratings at the 14-month follow-up were undiminished compared with ratings at 1 month after the sessions.

MacLean et al. (2011) analyzed the data from the two double-blind controlled studies of psilocybin reported by Griffiths et al. (2006, 2011). In particular, their goal was to use the NEO Personality Inventory to analyze possible personality changes that might have occurred after the high-dose psilocybin sessions in those studies. It is generally believed that personality traits are relatively enduring and that an individuals personality is predominantly stable across the lifespan. Yet evidence also exists that significant life events may dramatically change adult personality (see references in MacLean et al., 2011). The most widely accepted model of personality structure is the five-factor model, which describes five broad domains of personality: neuroticism, extroversion, openness, agreeableness, and conscientiousness (see references in MacLean et al., 2011). The authors suggest that numerous subjective claims of long-term changes after hallucinogen use appear to align with the personality trait of openness, which encompasses aesthetic appreciation and sensitivity, imagination and fantasy, and broad-minded tolerance of others viewpoints and values. Thus, they hypothesize that the mystical experiences reported in the studies by Griffiths et al. might lead to enduring increases in openness. Analysis of personality was assessed 1 to 2 months after a high-dose psilocybin session and again 16 months later to determine the persistence of any personality change(s). Consistent with their hypothesis, a mystical experience after psilocybin administration was significantly correlated with increases in openness. No such effect was seen after methylphenidate treatment. In addition, there were no significant changes in any of the other four personality factors after psilocybin administration. At the 16-month follow-up, openness levels still remained significantly elevated. The authors note that This is the first study to demonstrate changes in personality in healthy adults after an experimentally manipulated discrete event.

Studerus et al. (2011) pooled raw data from eight double-blind placebo-controlled experimental psilocybin studies conducted between 1999 and 2008. The data were analyzed for acute, short- and long-term subjective effects of psilocybin in 110 healthy human subjects who had received between one and four doses of 45315 g/kg psilocybin. Studerus et al. (2011) reported that nearly 40% of the participants in their laboratory studies of psilocybin claimed positive long-term changes in aesthetic experience and in their relationship with the environment (i.e., nature) after their psilocybin sessions. At 816 months after psilocybin sessions, more than 60% of subjects rated the experience as very enriching, and more than 90% described it as enriching to at least a medium degree. These effects occurred despite the fact that no attempt was made in their experiments to optimize conditions for a spiritual or mystical experience, which contrasts with the setting and preparations used in the two Griffiths studies cited above.

Bouso et al. (2012) compared 127 regular ayahuasca users with 115 actively religious controls who did not use ayahuasca. Baseline measurements were taken of general psychologic well-being, mental health, and cognition and the groups were then compared 1 year later to determine whether regular ayahuasca use had an effect on these measurements. Regular ayahuasca users showed lower scores on all psychopathology scales as assessed by the Symptom Checklist 90Revised, as well as on measures of harm avoidance and self-directedness. Participants scored higher on a measure of psychosocial well-being and performed better on the Stroop test (an indicator of resistance to emotional interference) and the Wisconsin Card Sorting Task (a measure of working memory). No evidence of psychologic maladjustment, mental health deterioration, or cognitive impairment was found in the ayahuasca-using group.

Lerner and Lyvers (2006) compared users of psychedelic drugs with users of nonpsychedelic drugs and nonillicit drugusing social drinkers. Samples were drawn from Israel and Australia. Compared with the other two groups, psychedelic drug users scored significantly higher on mystical beliefs (e.g., oneness with God and the universe), life values of spirituality, and concern for others, and scored lower on the value of financial prosperity, irrespective of culture of origin.

Lyvers and Meester (2012) carried out a website survey of 337 adults who used a variety of drugs, including psychedelics. Only about 25% reported spiritual motives for using psychedelics, yet use of high doses of LSD and psilocybin was significantly correlated in a dose-related manner with scores on two well known indices of mystical experiences; use of MDMA, cannabis, cocaine, opiates, or alcohol was not. Thus, even when taken recreationally, psychedelics have the potential to induce mystical experiences.

Quite interestingly, the underlying neuronal basis for mystical/spiritual experiences has recently been the subject of scientific investigation. Kometer et al. (2015) studied the neuronal basis of spiritual experiences and insightfulness after administration of psilocybin to human subjects. They conducted a double-blind, placebo-controlled study and administered psilocybin (170 or 215 g/kg, p.o.) to 50 healthy human volunteers. Electroencephalography (EEG) data were recorded from 64 scalp electrodes. Exact low-resolution brain electromagnetic tomography was applied to compute the three-dimensional intracerebral current density values of the scalp-recorded EEG rhythms. They used lagged phase synchronization, a new measure that can capture nonlinear neuronal relationships to assess dynamic functional connectivity (Pascual-Marqui et al., 2011).

The 11-dimension 5D-ASC questionnaire was used to quantify the subjective psychologic effects of psilocybin, with a particular interest in the spiritual experience subscale, and the related subscales of experience of unity, comprising experience of oneness with the environment and the self, insightfulness, measuring profound insights into life and existence, blissful state, measuring experiences of pleasure, inner peace, and love. Voxel-wise product-moment correlations between current source density in the psilocybin condition and the 11-dimension 5D-ASC subscale scores were computed by regression analysis.

Psilocybin significantly increased scores of all subscales on the 5D-ASC but significantly decreased current source density of oscillations in all frequency bands up to 20 Hz (eyes-closed condition) or up to 30 Hz (eyes-open condition). There was a significant and consistent psilocybin-induced reduction of current source density across low frequency bands (<20 Hz) in the posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC). Psilocybin decreased the current source density of neuronal 1.5- to 2.0-Hz oscillations within a neural network comprising the PCC, anterior cingulate cortex (ACC), and parahippocampal regions. The intensity of psilocybin-induced spiritual experience and insightfulness correlated with the lagged phase synchronization of 1.5-to 2.0-Hz oscillations between the RSC, parahippocampus, and lateral orbitofrontal area.

The extent of lagged phase synchronization within a network of deep cortical structures strongly and positively correlated with score on the insightfulness subscale of the 5D-ASC and spiritual experiences subscales of the 5D-ASC during the eyes-closed condition. Lagged phase synchronization of 1.5- to 4-Hz oscillations within a network comprising the RSC, parahippocampus, and lateral orbitofrontal area was associated with spiritual experiences and insightfulness.

These findings of Kometer et al. (2015) provide further evidence that decreased ongoing oscillations below 20 Hz, particularly / oscillations, may be a common mechanism of action of psychedelics. The decrease in lower frequency oscillations was found to be localized within an extended network that included the PCC, RSC, ACC, and parahippocampal regions, a network that strongly overlaps with the default mode network (DMN). Thus, psilocybin may modulate default mode functions by decreasing ongoing lower frequency oscillations within this network.

Lower frequency oscillations, particularly in the range, mediate rhythmic cortical inhibition of neuronal ensembles (see references in Kometer et al., 2015). The marked decrease in lower frequency oscillations observed in this study may indicate that psilocybin induces a shift of the resting excitation/inhibition balance toward excitation, which would be expected to disrupt the ordinary temporal structure of neuronal processes within the extended DMN.

Lagged phase synchronization was strongly associated with the psilocybin-induced state of consciousness, supporting the view that neural integration, rather than activity, underlies the state of consciousness. Scores of the spiritual experiences subscale of the 5D-ASC questionnaire were also associated with increased lagged phase synchronization of oscillations between parahippocampal regions and the RSC. Kometer et al., (2015) speculate that the neuronal network processes they identified may constitute a crucial pathway that can be modulated by serotonergic receptors to regulate mental health, a conclusion that would be consistent with some of the potential positive mental health outcomes discussed earlier in this section.

For decades, the media have largely portrayed psychedelics as extremely dangerous drugs; in fact, the classic serotoninergic psychedelics are generally considered very physiologically safe, certainly compared with opiates and psychostimulants. Jaffe (1985) stated, In man, deaths attributable to direct effects of LSD are unknown, and this statement remains true even today. Nonetheless, despite the relative physiologic safety of psychedelics, they can lead to serious psychologic consequences. In addition, as will be discussed later, some of the newer highly potent synthetic phenethylamine hallucinogens have proven to be unexpectedly toxic. This section will detail studies indicating that psychedelics can be safely used under supervision, and that few documented serious adverse effects occur even after recreational use. The discussion will then turn to some generally recognized adverse reactions, followed by case reports of some more serious and even fatal reactions to psychedelics. It should be emphasized that these latter fatalities, which are rare, have occurred after use of newer synthetic phenethylamine compounds, and not as a result of ingestion of LSD, psilocybin, mescaline, or DMT.

Analysis of early published reports on adverse reactions and long-term negative sequelae induced by classic psychedelics failed to identify significant adverse events; if long-term adverse effects from repeated use did occur, they were subtle or nonsignificant (Strassman, 1984; Halpern and Pope, 1999). Their reviews were based on reports from supervised clinical studies using pure drugs, so the same conclusions might not apply to recreational use of drugs with unknown identities or purity.

These substances do not lead to addiction or dependence and are not considered to be reinforcing (O'Brien, 2001). This is understandable when one realizes that the serotonergic hallucinogens do not have direct effects on brain dopaminergic systems, a pharmacology that appears essential for nearly all drugs that can engender dependence. Attempts to train animals to self-administer hallucinogens, an animal model that can predict abuse liability, have generally been unsuccessful.

Using 20012004 data drawn from the National Survey on Drug Use and Health (NSDUH), Krebs and Johansen (2013) recently evaluated possible associations between lifetime use of psychedelics and current mental health in the U.S. adult population. In a large sample of respondents, 13.4% reported lifetime psychedelic use. No significant associations were found between lifetime use of any psychedelic or past-year use of LSD and increased rate of any mental health outcome. Surprisingly, in several cases, use of psychedelics was associated with a lower mental health problem rate.

A statewide survey of the adult population in Colorado sought to determine whether psychedelic use was correlated with the lifetime risk of panic attacks (Bonn-Miller et al., 2007). No association was found between psychedelic use and panic attacks, but psychedelic abuse and dependence were significantly related to an increased lifetime risk of panic attacks. It should be noted that in this study, however, phencyclidine (PCP) was included in their survey as a psychedelic, and this substance, in contrast with the classic serotonergic psychedelics, can cause dependence.

Peyote (L. williamsii) is a small cactus that grows in the Southwestern United States and Northern Mexico. It contains the psychedelic compound mescaline and has been used for centuries by Native American populations in rituals and ceremonies. Mescaline is also found in the San Pedro and Peruvian Torch cacti, and these have also been used ceremonially. Although peyote is classified as a Schedule 1 controlled substance, members of the Native American Church have a legal exemption to use it in their religious services. Halpern et al. (2005) compared 61 Navajo Native American Church members who regularly ingested peyote with 79 individuals reporting minimal use of peyote, alcohol, or other substances. Cognitive function was assessed using the Rand Mental Health Inventory and 10 standard neuropsychological tests of memory and attentional/executive functions. The peyote-using group showed no significant deficits on the Rand Mental Health Inventory or on any of the 10 other tests used. For the peyote-using group, total lifetime peyote exposure was not associated with neuropsychological performance.

By contrast, recreational use of peyote has led to adverse events, although peyote exposures reported to poison control centers are relatively rare compared with other drugs of abuse. In 2007, for example, only 116 peyote or mescaline exposures were reported to U.S. poison control centers out of more than 2.4 million total drug exposures (Bronstein et al., 2008). Carstairs and Cantrell (2010) retrospectively reviewed the California Poison Control System electronic database between the years 1997 and 2008 for reports of cases involving adverse reactions to peyote or mescaline ingestion when it was the sole intoxicating agent. A total of 31 cases were identified that met their inclusion criteria. Life-threatening symptoms did not occur, and most exposures were associated with only mild to moderate clinical effects, which most commonly included tachycardia and central nervous system (CNS) effects. Symptoms typically resolved within 24 hours or less and did not usually require anything more than supportive measures or sedation. One case of a prolonged peyote-induced psychosis was reported by Lu et al. (2004), in which the psychosis resolved after sleep. The case involved a 54-year-old Native American man with no prior history of psychosis. He drank peyote juice during a healing ceremony and within a few hours became convinced that he was hunted by animal spirits. He was unable to sleep for 2 weeks, at which time he developed visual and auditory hallucinations of the spirits and became increasingly depressed. He was persuaded to enter a hospital, where he received trazodone to help him sleep. He fell asleep and slept for 15 hours, which led to complete resolution of his psychotic symptoms. The authors speculated that his psychosis was a result of his prolonged sleep deprivation.

Hasler et al. (2004) studied eight subjects given either placebo or 45, 115, 215, or 315 g/kg psilocybin (a very low, low medium, or high dose, respectively). Instruments used to assess psilocybin effects included the 5D-ASC, the Frankfurt Attention Inventory (FAIR), and the Adjective Mood Rating Scale (AMRS). Several physiologic and plasma hormones were also measured. Psilocybin dose-dependently increased all measures on the 5D-ASC. The medium and high doses of psilocybin led to a 50% reduction in performance on the FAIR test. The only scores that were increased on the AMRS were general inactivation, emotional excitability, and dreaminess. Hasler et al. (2004) found no evidence that psilocybin is hazardous with respect to somatic health.

Bouso et al. (2015) used magnetic resonance imaging to examine potential differences in cortical thickness in 22 Spanish regular users of ayahuasca, compared with 22 matched controls. Inclusion criterion for ayahuasca users was that they had used it at least 50 times in the 2 previous years. Subjects also were assessed using three neuropsychological tests, including the two-back test to assess working memory, the Wisconsin Card Sorting Test to assess executive function, and a switching task to assess set shifting. Personality was also assessed by self-report using the Spanish version of the Temperament and Character InventoryRevised questionnaire. Ayahuasca users scored significantly better than controls on several variables derived from the neuropsychological tests. No increased psychopathology or worse neuropsychological performance was observed in the ayahuasca group, consistent with findings reported earlier by Grob et al. (1996) for ayahuasca users who were members of the Brazilian church, the UDV. Indeed, ayahuasca users scored significantly better than controls on harm avoidance, and its subscale anticipatory worry, and significantly higher on self-transcendence. Cortical thinning was found for six brain areas in the ayahuasca group: the middle frontal gyrus, the inferior frontal gyrus, the precuneus, the superior frontal gyrus, and the PCC. By contrast, cortical thickening was seen in the precentral gyrus and the ACC. Correlation analysis revealed that lifetime use of ayahuasca was inversely correlated to cortical thickness in the PCC.

Although there is a general public perception that psychedelic drugs are dangerous, from a physiologic standpoint they are in fact one of the safest known classes of CNS drugs. They do not cause addiction, and no overdose deaths have occurred after ingestion of typical doses of LSD, psilocybin, or mescaline. Cohen (1967) and Jaffe (1985) have both stated that death due to direct LSD toxicity is unknown. Indeed, recreational users who have consumed massive doses of LSD have survived. For example, eight individuals who believed they had cocaine accidentally insufflated an extremely high dose of LSD. Their plasma LSD levels were reported as between 1000 and 7000 g/100 ml (recall that a typical total oral dose of LSD might be 100200 g). These individuals all became comatose, with hyperthermia, vomiting, light gastric bleeding, and respiratory problems. With hospital treatment, however, all eight survived and without apparent residual effects (Klock et al., 1974).

Although the classic psychedelics have not been directly responsible for causing death, the judgment of users is certainly impaired while under the influence of these drugs. This is a particular concern when hallucinogens are used in unsupervised settings. Users may believe that they are invincible or possess superpowers and may do things they would not normally consider, such as believing they can fly (Reynolds and Jindrich, 1985), jumping from buildings (Keeler and Reifler, 1967), or incurring severe ocular damage by prolonged staring at the sun (Schatz and Mendelblatt, 1973; Fuller, 1976).

Studerus et al. (2010) analyzed acute, short-, and long-term subjective effects of psilocybin in healthy humans. Again, using pooled raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008, their analysis included 110 healthy subjects who had received between one and four oral doses of psilocybin (45315 g/kg body weight). Psilocybin dose-dependently induced profound changes in mood, perception, thought, and self-experience, but most subjects described the experience as pleasurable, enriching, and nonthreatening. Acute adverse reactions were characterized by strong dysphoria and/or anxiety/panic, but occurred only at the two highest doses of psilocybin in a relatively small number of subjects. All acute adverse drug reactions were successfully managed through interpersonal support and did not require psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis, or other long-term impairment of functioning in any of the subjects. The results indicate that the administration of modest psilocybin doses to healthy, high-functioning, and well prepared subjects in the context of a carefully monitored research environment carries an acceptable level of risk.

The recent resurgence of interest in the clinical uses of psychedelics led Johnson et al. (2008) to propose appropriate procedures for using them in clinical practice. The guidelines they outline have certain parallels with ritual uses of hallucinogens by older indigenous cultures. In particular, Johnson et al. (2008) cite the need for structured use (expressed as ritual in indigenous use) and restrictions on use, including the need for guidance and appreciation of the powerful psychologic effects of hallucinogens (expressed as reverence in indigenous use). Psychedelic administration in humans results in a unique profile of effects and potential adverse reactions that need to be appropriately addressed to maximize safety. The primary safety concerns with psychedelics are largely psychologic rather than physiologic in nature. Somatic effects vary but are relatively insignificant, even at doses that elicit powerful psychologic effects. The proposed guidelines extend and complement the recommendations of Fischman and Johanson (1998) for high-dose hallucinogen research. The guidelines include 1) the presence of two monitors with some medical knowledge, knowledge of ASCs, and a degree of clinical sensitivity; 2) a physical environment that is safe, aesthetically pleasing, and comfortable; 3) careful subject preparation, including several meetings to establish rapport and trust with the monitors; 4) a detailed consent form and explanations of the study procedures, detailed discussions about the range of potential experiences, and time of onset and duration of the effects; and 5) an available physician in the event of an untoward medical reaction. Anyone contemplating carrying out a clinical research program with a psychedelic is strongly encouraged to read the detailed guidelines presented by Johnson et al. (2008).

Krebs and Johansen (2013) evaluated any association between lifetime use of psychedelics and current mental health in the adult population. Data were analyzed for 20012004 for 130,152 randomly selected NSDUH respondents; 21,967 respondents (13.4% weighted) reported lifetime psychedelic use. The authors found no significant association between lifetime use of any psychedelic and increased rate of any mental health outcomes. Indeed, they discovered that psychedelic use was associated with a lower rate of mental health problems in several cases. Johansen and Krebs (2015) subsequently analyzed a new data set of 135,095 randomly selected U.S. adults that included 19,299 users of psychedelics. Data were from the NSDUH for 20082011. As in their earlier study, the authors found no significant associations between lifetime use of psychedelics and increased likelihood of past-year serious psychologic distress, mental health treatment, depression, anxiety, or suicidal thoughts, plans, or attempts. Johansen and Krebs (2015) failed to find any evidence that use of psychedelics is an independent risk factor for mental health problems. Indeed, they report that lifetime use of psychedelics was associated with decreased inpatient psychiatric treatment.

Hendricks et al. (2014) analyzed data from 20022007 for 25,622 individuals charged with a felony in the Southeastern United States and under community corrections supervision in the Treatment Accountability for Safer Communities program, which is a case management intervention program for individuals with a history of substance involvement. The authors examined relationships between any hallucinogen use disorder (versus no hallucinogen use disorder) and all available sociodemographic and psychosocial variables. They report that any hallucinogen use disorder was associated with a decreased probability of supervision failure. They note the contrast with any cannabis, cocaine, alcohol, opiate, or amphetamine use disorder, each of which was associated with an increased probability of supervision failure. Their results suggest that hallucinogens may promote alcohol and other drug abstinence and prosocial behavior in a population with high rates of recidivism.

In a more recent report by Hendricks et al. (2015), the authors evaluated any relationship between use of a classic psychedelic and psychologic distress and suicidality among more than 190,000 U.S. respondents pooled from the NSDUH for 20082012. Lifetime use of a psychedelic was associated with significantly reduced odds of past-month psychologic distress, past-year suicidal thinking, past-year suicidal planning, or past-year suicide attempt. By contrast, lifetime use of other illicit drugs was associated with an increased likelihood of these outcomes. The authors suggest that classic psychedelics may hold promise in the prevention of suicide. These findings are consistent with the surveys of Krebs and Johansen (2013) and Johansen and Krebs (2015); in all three studies, the authors suggest that their data are not compatible with the highly restricted legal status of psychedelics and that more extensive clinical research is warranted.

Use of high doses of psychedelics can lead to vascular problems because the 5-HT2A receptor is associated with vascular smooth muscle contraction, platelet aggregation, thrombus formation, and coronary artery spasms (Nagatomo et al., 2004). Acute vasoconstriction caused by serotonin is usually shared by activation of 5-HT1B and 5-HT2A receptors; however, in intracranial arteries, only the 5-HT1B receptor mediates constriction (Kaumann and Levy, 2006). Both 5-HT2A and 5-HT1B receptors can mediate coronary artery spasm. 5-HT2A receptors also constrict the portal venous system, including esophageal collaterals in cirrhosis. Data from studies by Ootsuka et al. (2004) suggest that spinal 5-HT2A receptors contribute to sympathetically induced cutaneous vasoconstriction regulated by the raphe/parapyramidal neurons in the brainstem.

Balkov (2005) reports a fatal and nonfatal overdose after ingestion of the psychedelic phenethylamine 2,5-dimethoxy-4-bromoamphetamine (DOB) by two male individuals. Gas chromatographymass spectrometry was used to detect the presence of DOB in both gastric and urine samples of the two men. Although one subject survived, the other suffered convulsions and metabolic acidosis and died 6 days after admission.

Psilocybin, when administered in a controlled setting, has frequently been reported to cause transient, delayed headache, with incidence, duration, and severity increased in a dose-related manner (Johnson et al., 2012). Bickel et al. (2005) reported the case of a 25-year-old hepatitis Cinfected man, who presented with severe rhabdomyolysis and acute renal failure after Psilocybe mushroom ingestion. He later developed encephalopathy with cortical blindness. Respiratory and cardiovascular support, mechanical ventilation, continuous venovenous hemodialysis, and corticosteroid treatment led to improvement and the patient recovered completely over several months.

Psilocin was identified in the urine of a subject who was investigated for driving under the influence (Tiscione and Miller, 2006). The subject apparently did not exhibit any response to the crash of his automobile, seemingly unaware of the severity of his situation or immediate surroundings.

Although very rare, there have been reports of rhabdomyolysis after ingestion of LSD (Berrens et al., 2010). A newer tryptamine, 5-methoxy-N,N-diisopropyltryptamine (foxy) also produced rhabdomyolysis and transient acute renal failure in an otherwise healthy 23-year-old man (Alatrash et al., 2006).

Although many ergot alkaloids are known to produce vasospasm, especially after chronic use, LSD has rarely been associated with this adverse effect. Nevertheless, Raval et al. (2008) reported on a 19-year-old woman who experienced severe lower-extremity ischemia related to a single use of LSD 3 days prior to presentation. After intra-arterial nitroglycerin and verapamil failed, balloon percutaneous transluminal angioplasty therapy led to rapid clinical improvement in lower-extremity perfusion. As of the date of the report, the patient had not required a major amputation.

Sunness (2004) described a 15-year-old female patient with a 2-year history of afterimages and photophobia after a history of drug use that included LSD, marijuana, and other illicit drugs. She had discontinued LSD 1 year prior to examination. Although the author connected her visual problems with her prior LSD use, it is not at all clear from the report that her LSD use was the cause of her visual problem.

Bernhard and Ulrich (2009) reported a case of cortical blindness in a 15-year-old girl. She had headache and nausea 5 days after taking LSD and suddenly developed complete blindness in both eyes. The blindness persisted for 48 hours. Over the next 3 months, the subject had three more episodes of complete blindness that lasted 1236 hours, with no visual disturbances between episodes. The authors suggested that the temporary blindness might be a correlate of flashbacks caused by LSD.

Toxicity also has been noted for several of the so-called designer drugs. For example, Jovel et al. (2014) reported the case of a healthy young male individual who ingested 5-methoxy-N,N-diallytryptamine, one of the emerging new tryptamine-type research chemicals. The patient was admitted with extreme agitation, tachycardia, diaphoresis, and combativeness that required physical restraint and intravenous sedation, but the patient did recover.

Andreasen et al. (2009) reported a fatality involving the potent synthetic psychedelic phenethylamine compound 1-(8-bromobenzo[1,2-b; 4,5-b]difuran-4-yl)-2-aminopropane, known commonly as Bromo-Dragonfly. An 18-year-old woman was found dead after ingesting 1 ml of a hallucinogenic liquid. She and her boyfriend had ingested it between 10 and 11 PM on the previous evening and then they both fell asleep. On awakening at 5 AM the next morning, the womans boyfriend discovered that she was dead. Autopsy findings 3 days after her death included edema of the lungs, slight edema of the brain, spleen enlargement, irritation of the mucous membrane in the stomach, and ischemic changes in the kidneys. Her femoral blood concentration of the drug was 4.7 g/kg. The bottle containing the hallucinogenic liquid was recovered and analyzed by ultraperformance liquid chromatography time-of-flight mass spectrometry, high-performance liquid chromatography diode array detection, 1H nuclear magnetic resonance, and 13C nuclear magnetic resonance and found to contain a solution of almost pure Bromo-Dragonfly. Based on the solution concentration and the amount of solution consumed, it was estimated that she had ingested approximately 700 g. Although that would seem to be a relatively small dose, no other drugs were discovered in her system, including the absence of ethanol.

It is often difficult to establish whether the drug is pure or has been coingested with other unknown drugs of unknown purity. For example, Ovaska et al. (2008) reported a case of sympathomimetic toxicity in a patient who was reported to have ingested 2,5-dimethoxy-4-chloroamphetamine (DOC), yet toxicological screening showed the patient had ingested both DOC and MDMA.

Data for 2005 to 2006 from the Texas Poison Control Centers were reviewed for mushroom exposures (Barbee et al., 2009). There were a total of 742 exposures, which were all acute and intentional. Of those, 59 individuals were admitted to a hospital, with 17 requiring admission to a critical care unit. Nonetheless, only 10 of the admissions that were identified involved psilocybin. Of all of the admissions, major toxic reactions were uncommon, with no deaths reported.

One adverse effect of hallucinogen use, particularly associated with LSD use, is hallucinogen persisting perception disorder (HPPD). This term has displaced an earlier somewhat more nonspecific one known as flashbacks, which was a re-experiencing of one or more of the perceptual effects induced by a hallucinogen at some later time, after the acute drug effects had worn off. HPPD is composed of afterimages, perception of movement in peripheral visual fields, blurring of small patterns, halo effects, and macro- and micropsia long after the drug has been used.

The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), Text Revision lists the following three criteria for HPPD: A) re-experiencing, after the use of a hallucinogen, of one or more of the perceptual symptoms that were experienced while intoxicated with the hallucinogen; B) the symptoms in criterion A cause clinically significant distress or impairment in social, occupational, or other important areas of functioning; and C) the symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

Halpern and Pope (2003) noted that when LSD was used in a therapeutic or research setting, HPPD appeared less frequently than when LSD was used recreationally. The authors concluded, however, that some individuals, especially users of LSD, can experience a long-lasting HPPD syndrome with symptoms of persistent perceptual abnormalities reminiscent of acute intoxication. Nevertheless, the incidence of HPPD is very small given the many tens of millions of persons who have taken LSD, most often in a recreational setting. Litjens et al. (2014) provided a recent comprehensive review on the subject of HPPD. The actual incidence of HPPD is not known and depends on the prevalence of use in different countries, but epidemiologic information is scarce.

Hermle et al. (2008) reviewed MEDLINE data for 19972007, searching for reports of hallucinogen-induced psychosis, flashbacks, and HPPD. The authors reported that adolescent intoxication with psychedelic drugs rarely produced acute psychotic syndromes, further stating that The clinical relevance of flashback phenomena as a post-hallucinogenic psychiatric disorder has to be disputed.

Although LSD was most widely used and therefore has led to the greatest number of HPPD cases, it is clear that other hallucinogens also can evoke the syndrome. For example, Espiard et al. (2005) reported HPPD in an 18-year-old man after mixed intoxication with psilocybin and cannabis. The symptoms persisted for more than 8 months. Ikeda et al. (2005) reported flashbacks after use of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) by a 35-year-old man without a previous psychiatric history. He had used the substance six or seven times over 5 months but discontinued it after he had a bad trip, with anxiety, palpitations, auditory oversensitiveness, and visual distortions. Treatment with oral risperidone ameliorated his symptoms. Another case study described a 33-year-old woman who developed HPPD after LSD use for a year. Although treatment with antidepressants and risperidone did not ameliorate her symptoms, treatment with the antiseizure drug lamotrigine almost completely abolished her visual disturbances (Hermle et al., 2012).

Although the classic serotonergic hallucinogens are not recognized to be particularly toxic, a new class of substituted phenethylamines with toxic properties has recently become very popular as recreational drugs (Nikolaou et al., 2014). Unfortunately, there are now several reports of hospitalizations and fatalities attributed to these compounds (Poklis et al., 2013, 2014; Rose et al., 2013; Nikolaou et al., 2014; Tang et al., 2014; Walterscheid et al., 2014), but it is not clear whether deaths resulted from ingestion of lethal amounts of pure bulk drug or whether the drug has some inherent toxicity that is not normally associated with other psychedelics.

Suzuki et al. (2015) provided a comprehensive literature review of toxicities associated with NBOMe ingestion. The most common adverse reactions were agitation (including aggressiveness), tachycardia, and hypertension, with seizures reported in 40% of the patients. In the 20 individual cases they reviewed, 3 (15%) were fatalities.

The most potent of these new recreational chemicals are shown in Fig. 3, with potency increasing going from X = H to X = I.

For purposes of law enforcement the iodo compound (X = I; 25I-NBOMe) is presently considered by the U.S. Drug Enforcement Administration to be an analog of 2C-I [2-(4-iodo-2,5-dimethoxy)aminoethane], which is currently a Schedule 1 controlled substance. The procedure to classify 25I-NBOMe as a Schedule 1 substance has been initiated and it has been placed temporarily into Schedule 1 (Drug Enforcement Administration, 2013). Global interest in these compounds and closely related analogs has attracted increasing interest. For example, the European Monitoring Centre for Drugs and Drug Addiction has received a range of notifications from European Union member states about analytically confirmed nonfatal and fatal intoxications associated with 25I-NBOMe. This was followed by a risk assessment conducted by the European Monitoring Centre for Drugs and Drug Addiction Scientific Committee to assess health and social risks associated with the iodo analog (European Monitoring Centre for Drugs and Drug Addiction, 2014). In addition, the World Health Organizations Expert Committee on Drug Dependence reviewed the status of a range of new substances for its 36th meeting in June 2014, which included 25I-NBOMe and its 4-bromo and 4-chloro analogs (World Health Organization, 2014).

In the mouse head-twitch assay, 25I-NBOMe and a related analog were extremely potent in inducing this behavior, which was blocked by preadministration of the selective 5-HT2A antagonist M100907 [(R)-(+)-a-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol] (Halberstadt and Geyer, 2014). As discussed in the section on mouse models later in this review, the mouse head twitch has shown a high correlation with human psychedelic activity.

A relatively large series of 48 NBOMe-type compounds has been evaluated for affinity and function at 5-HT2 family receptors (Hansen et al., 2014). Their work was directed toward development of potential radioligands for in vivo PET imaging of 5-HT2A receptors that would be selective over 5-HT2C receptors. One compound was discovered that had approximately 100-fold selectivity for both affinity and function at the 5-HT2A versus 5-HT2C receptor. Their high affinity and relative selectivity for the 5-HT2A receptor has made some of these compounds useful as agonist ligands for in vivo PET imaging (Ettrup et al., 2010; Finnema et al., 2014).

Curiously, the NBOMe-type compounds do not appear to be orally active and are typically administered bucally, or by nasal insufflation. Their potency is so high that they are often distributed on blotter papers and marketed as being LSD. Users place the blotters against their gums to effect absorption. One hypothesis put forward to explain the lack of oral activity for these highly active compounds is a significant first-pass metabolic effect (Leth-Petersen et al., 2014). In that study, the microsomal stability of 11 phenethylamines and their N-benzylated congeners was studied using human liver microsomes. It was found that the N-benzylated compounds had a much higher intrinsic clearance than did the simple phenethylamines, and the authors hypothesized that their low hepatic stability was the reason for their lack of oral activity.

Stellpflug et al. (2014) reported a clinical case of a nonfatal overdose with 25I-NBOMe. They identified a major metabolite of the compound in the urine that had a concentration 80-fold higher than the parent drug. The subjects urine was treated with -glucuronidase and then analyzed using ultraperformance liquid chromatography electrospray ionization plus tandem mass spectrometry to identify a major metabolite with a mass that was one methyl group lower than the parent compound. Comparison of the full fragmentation pattern was then assessed and concluded to be an O-demethylated metabolite at the 2- or 5-position of the trisubstituted ring, but the investigators were not able to determine which position had been metabolized. They detected two other very minor metabolites that also appeared to be O-demethylated. The concentration of the unmetabolized parent 25I-NBOMe in the urine was 7.5 ng/ml, whereas the desmethyl metabolite was 600 ng/ml. This metabolite and the two other minor metabolites were not present in the urine in the absence of prior enzymatic treatment, indicating that they were all glucuronidated.

Most recently, Leth-Petersen et al. (2015) identified the basis for the high first-pass effect of NBOMe compounds and the likely basis for their inactivity after oral administration. Using in vivo studies in pigs, they determined that the 5-methoxy of the trisubstituted phenyl ring is rapidly O-demethylated. After intravenous administration of 25B-NBOMe [N-(2-[11C]methoxybenzyl)-2,5-dimethoxy-4-bromophenethylamine (Cimbi-36)] to a pig, analysis revealed that plasma levels of the parent drug rapidly declined, with a new metabolite rapidly appearing and accumulating in plasma. At the 30-minute mark, there was more than twice as much of this metabolite present in plasma as there was of the parent compound. This metabolite was definitively identified as the 5-O-glucuronide using liquid chromatography/mass spectrometry and chemical synthesis. Evidently, the highly hydrophobic nature of the N-benzyl phenethylamines readily targets them to the mixed function oxidases in the endoplasmic reticulum, where they are efficiently 5-O-demethylated and then very quickly glucuronidated.

Stanislov Grof characterized LSD as a powerful nonspecific amplifier of the unconscious (Grof, 1975). This empirical observation was based on his personal supervision of more than a thousand clinical administrations of LSD. Barr et al. (1972) also stated that the phenomena induced by LSD cannot be predicted or understood in purely pharmacological terms; the personality of the drug taker plays an enormous and critical role in determining how much effect there will be and of what particular type.

However, until we understand the fundamental nature of consciousness and its underlying neuronal substrates, as well as the unconscious, it will not be possible to scientifically test Grofs hypothesis. What can be discussed are the findings that point to involvement of specific receptors in certain brain areas that lead to the overt effects of psychedelics. In addition, recent brain scanning technologies, including PET, fMRI, EEG, magnetoencephalography (MEG), and pharmacological magnetic resonance imaging (phMRI), have also allowed the identification of key brain areas that must be involved in the actions of psychedelics.

One should keep in mind that the effects of psychedelics are highly variable and are not necessarily dose dependent. At low doses of LSD (e.g., <100 g), sensory and cognitive processes may be distorted and altered but the user generally remains aware that the effects are attributable to having ingested the drug. For the purposes of clinical investigations, such doses allow the use of various questionnaires, instruments, and interviews to determine the intensity and qualitative aspects of the drug effect. Even lower doses of LSD are popular for recreational use or group events in which the user wishes to remain in contact with their surroundings.

By contrast, high doses have a greater propensity to transport the user to an alternate reality, where they lose contact with their everyday environment. These occasions are often described as peak experiences, transcendent, or mystical and are profoundly altered states of consciousness. Users may feel that they have transcended time and space or encountered their concept of God, or they may feel that they have encountered otherworldly beings, feelings of being at one with the universe, reliving past memories, and so forth. With respect to medical value, this state of consciousness is most closely associated with dramatic therapeutic improvement. Although this phenomenon is more likely to occur after high doses of psychedelics, it can occur at nearly any dose if the set and setting have been optimized to promote such an ASC. These experiences are often characterized as among the most meaningful of the subjects life (e.g., see Griffiths et al., 2006) and can lead to persisting positive effects on attitudes, mood, and behavior.

It was only a decade after the discovery of the remarkable psychopharmacology of LSD that the presence of serotonin was demonstrated in the mammalian brain (Twarog and Page, 1953). A comparison of the chemical structures of LSD and serotonin (shown earlier) led to early hypotheses that the action of LSD was due to an interaction with serotonin systems in the brain. Ten years after the discovery of LSD, Gaddum (1953) reported that LSD antagonized the action of serotonin in peripheral tissues. Only 1 year later, Gaddum and Hameed (1954) and Woolley and Shaw (1954) independently proposed that the effects of LSD might result from serotonin receptor blockade in the CNS. Shaw and Woolley (1956) later modified their hypothesis to include the possibility that LSD might mimic the actions of serotonin. Numerous studies in the subsequent decade examined the possibility that LSD blocked the actions of serotonin, but it was a concept that proved untenable. It was clear, however, that LSD did have a potent effect on brain serotonin systems, elevating whole brain serotonin content (Freedman, 1961) and reducing brain levels of the major metabolite of serotonin, 5-hydroxyindole acetic acid (Rosecrans et al., 1967).

Ultimately, Andn et al. (1968) suggested that LSD might have direct agonist actions at serotonin receptors in the brain. Subsequently, studies from numerous laboratories provided support for that idea, with an initial focus on serotonin 5-HT1A receptors (see discussion in Nichols, 2004). When serotonin receptorselective antagonists became available, it was Glennon et al. (1983, 1984) who demonstrated in a rat drug discrimination model that the 5-HT2 antagonists ketanserin and pirenperone blocked the discriminative cue of a psychedelic. Further studies in numerous laboratories over the next 2 decades, primarily with rodents, then focused attention on the 5-HT2A receptor as the primary target for psychedelics. Agonist or partial agonist activity at the serotonin 5-HT2A receptor was ultimately concluded to be a necessary pharmacology for psychedelic effects, but it may not be sufficient to explain all of the qualitative differences between different drugs. As Ray (2010) pointed out, different molecules may also have significant affinity for other types of brain receptors.

The first definitive experiment pointing to the central role of the 5-HT2A receptor for the action of psychedelics in humans came from a clinical study by Vollenweider et al. (1998), who showed that the effects of psilocybin were blocked by the 5-HT2A receptorselective antagonist ketanserin or the atypical antipsychotic risperidone but were enhanced by the dopamine antagonist and typical antipsychotic haloperidol. These data provided the first evidence that psilocybin-induced effects in humans were due to 5-HT2A receptor activation. Subsequently, Vollenweider and colleagues have carried out several additional clinical studies, discussed later, of various aspects of the action of psilocybin and have shown that ketanserin can block most of those effects.

Kometer et al. (2012) carried out a randomized, double-blind study in 17 healthy human subjects. On 4 separate days, subjects received placebo, psilocybin (215 g/kg), the 5-HT2A antagonist ketanserin (50 mg, p.o.), or psilocybin plus ketanserin. Mood states were assessed, and behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal-directed behavior toward emotional cues. Psilocybin was found to enhance positive mood and attenuate negative facial expression recognition. Furthermore, psilocybin increased goal-directed behavior toward positive compared with negative cues, facilitated positive but inhibited negative sequential emotional effects, and valence-dependently attenuated the P300 component. Ketanserin given alone had no effect but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression. This study demonstrated that psilocybin shifts the emotional bias across various psychologic domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects. The authors suggest that their findings have implications not only for the pathophysiology of dysfunctional emotional biases, but they may also provide a framework to delineate the mechanisms underlying psilocybins putative antidepressant effects.

Quednow et al. (2012) investigated the role of 5-HT2A receptors in automatic (sensorimotor gating) and controlled (Stroop interference) inhibition processes in a model psychosis approach using psilocybin (260 g/kg) in 16 healthy humans pretreated either with the 5-HT2Aselective receptor antagonist ketanserin (40 mg) or placebo, using a placebo-controlled, crossover, counterbalanced, and double-blind design. They found that psilocybin-induced deficits in automatic and controlled inhibition were significantly attenuated by ketanserin. They also replicated their previous findings that most of the subjective hallucinogenic effects of psilocybin were abolished by ketanserin.

Kometer et al. (2013) assessed the effects of psilocybin (215 g/kg) on both oscillations that regulate cortical excitability and early visual evoked P1 and N170 potentials in 16 healthy human subjects. They employed a double-blind, placebo-controlled, within-subject, randomized design. Psilocybin generally significantly increased 5D-ASC scores after placebo pretreatment, but not after ketanserin pretreatment. Psilocybin strongly decreased both prestimulus parieto-occipatal power and decreased N170 potentials associated with the appearance of visual perceptual alterations, including visual hallucinations. Preadministration of the 5-HT2A antagonist ketanserin (50 mg) blocked all of these effects. The authors conclude that 5-HT2A receptor activation by psilocybin profoundly modulates the neurophysiological and phenomenological indices of visual processing. They further propose that 5-HT2A receptor activation may induce a processing mode in which stimulus-driven cortical excitation is overwhelmed by spontaneous neuronal excitation through modulation of oscillations.

Indirect evidence for a role of 5-HT2A receptors in mediating psychedelic-induced hallucinations comes from a study by Huot et al. (2010). In that study, [3H]ketanserin binding was used to compare 5-HT2A receptor density in postmortem brains of patients with Parkinsons disease (PD) who experienced visual hallucinations with the brains of PD patients who did not experience hallucinations. Six brains from patients with idiopathic PD who experienced visual hallucinations were compared with six PD patients without visual hallucinations and five healthy, age-matched controls. In PD patients with visual hallucinations, [3H]ketanserin binding was increased 45.6% in inferolateral temporal cortex compared with PD patients who did not have visual hallucinations. The authors suggest that increased 5-HT2A density in the inferolateral temporal cortex may be the basis for visual hallucinations in PD patients and that 5HT2A antagonists may alleviate this symptom.

Similarly, Ballanger et al. (2010) measured 5-HT2A binding in vivo using [18F]setoperone PET in brains of seven PD patients with visual hallucinations and seven age-matched PD patients without visual hallucinations. Patients with visual hallucinations had significantly increased 5-HT2A receptor binding in several cortical regions and one subcortical region. These increased levels of 5-HT2A receptor expression were clustered mainly in the ventral visual pathway. With the evidence of increased 5-HT2A receptor expression as a possible basis for visual hallucinations in PD patients, a serotonin 5-HT2A inverse agonist, perhaps not surprisingly, demonstrated phase 3 clinical efficacy in treating several symptoms of PD psychosis, including visual hallucinations (Hacksell et al., 2014).

Halberstadt et al. (2011a) examined the effects of several psychedelics on the mouse head twitch response (HTR) in wild-type (WT) male C57BL/6J or 5-HT2A knockout (KO) mice. They also assessed investigatory and locomotor activity in the mouse behavioral pattern monitor (BPM). Psilocin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) produced the HTR in WT mice but not in KO mice. Psilocin and 5-MeO-DMT reduced locomotor activity, investigatory behavior, and center duration in the BPM, and these effects were blocked by the selective 5-HT1A antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridyl)cyclohexanecarboxamide), indicating that psilocin and 5-MeO-DMT act as mixed 5-HT1A/5-HT2A agonists. Halberstadt and Geyer (2011) reviewed the extensive literature covering various indoleamines as well as LSD and concluded that although the phenethylamines primarily exert their effects through activation of 5-HT2A receptors, indoleamines can have a significant behavioral component mediated by activation of 5-HT1A receptors.

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Psychedelics - Pharmacological Reviews

Psychedelia – Wikipedia

Psychedelia is the subculture, originating in the 1960s, of people who often use psychedelic drugs such as LSD, mescaline (found in peyote) and psilocybin (found in some mushrooms). The term is also used to describe a style of psychedelic artwork and psychedelic music. Psychedelic art and music typically try to recreate or reflect the experience of altered consciousness. Psychedelic art uses highly distorted and surreal visuals, bright colors and full spectrums and animation (including cartoons) to evoke and convey to a viewer or listener the artist's experience while using such drugs, or to enhance the experience of a user of these drugs. Psychedelic music uses distorted electric guitar, Indian music elements such as the sitar, electronic effects, sound effects and reverberation, and elaborate studio effects, such as playing tapes backwards or panning the music from one side to another.

The term "psychedelic" is derived from the Ancient Greek words psych (, "soul") and dloun (, "to make visible, to reveal"),[1] translating to "soul-revealing".

A psychedelic experience is characterized by the striking perception of aspects of one's mind previously unknown, or by the creative exuberance of the mind liberated from its ostensibly ordinary fetters. Psychedelic states are an array of experiences including changes of perception such as hallucinations, synesthesia, altered states of awareness or focused consciousness, variation in thought patterns, trance or hypnotic states, mystical states, and other mind alterations. These processes can lead some people to experience changes in mental operation defining their self-identity (whether in momentary acuity or chronic development) different enough from their previous normal state that it can excite feelings of newly formed understanding such as revelation, enlightenment, confusion, and psychosis.

Psychedelic states may be elicited by various techniques, such as meditation, sensory stimulation[2] or deprivation, and most commonly by the use of psychedelic substances. When these psychoactive substances are used for religious, shamanic, or spiritual purposes, they are termed entheogens.

The term was first coined as a noun in 1956 by psychiatrist Humphry Osmond as an alternative descriptor for hallucinogenic drugs in the context of psychedelic psychotherapy.[3] Seeking a name for the experience induced by LSD, Osmond contacted Aldous Huxley, a personal acquaintance and advocate for the therapeutic use of the substance. Huxley coined the term "phanerothyme," from the Greek terms for "manifest" () and "spirit" (). In a letter to Osmond, he wrote:

To make this mundane world sublime,Take half a gram of phanerothyme

To which Osmond responded:

To fathom Hell or soar angelic,Just take a pinch of psychedelic[4]

It was on this term that Osmond eventually settled, because it was "clear, euphonious and uncontaminated by other associations."[5] This mongrel spelling of the word 'psychedelic' was loathed by American ethnobotanist Richard Evans Schultes, but championed by Timothy Leary, who thought it sounded better.[6] Due to the expanded use of the term "psychedelic" in pop culture and a perceived incorrect verbal formulation, Carl A.P. Ruck, Jeremy Bigwood, Danny Staples, Jonathan Ott, and R. Gordon Wasson proposed the term "entheogen" to describe the religious or spiritual experience produced by such substances.[7]

From the second half of the 1950s, Beat Generation writers like William Burroughs, Jack Kerouac and Allen Ginsberg[8] wrote about and took drugs, including cannabis and Benzedrine, raising awareness and helping to popularise their use.[9] In the same period Lysergic acid diethylamide, better known as LSD, or "acid" (at the time a legal drug), began to be used in the US and UK as an experimental treatment, initially promoted as a potential cure for mental illness.[10] In the early 1960s the use of LSD and other hallucinogens was advocated by proponents of the new "consciousness expansion", such as Timothy Leary, Alan Watts, Aldous Huxley and Arthur Koestler,[11][12] their writings profoundly influenced the thinking of the new generation of youth.[13] There had long been a culture of drug use among jazz and blues musicians, and use of drugs (including cannabis, peyote, mescaline and LSD[14]) had begun to grow among folk and rock musicians, who also began to include drug references in their songs.[15][nb 1]

By the mid-1960s, the psychedelic life-style had already developed in California, and an entire subculture developed. This was particularly true in San Francisco, due in part to the first major underground LSD factory, established there by Owsley Stanley. There was also an emerging music scene of folk clubs, coffee houses and independent radio stations catering to a population of students at nearby Berkeley, and to free thinkers that had gravitated to the city.[18] From 1964, the Merry Pranksters, a loose group that developed around novelist Ken Kesey, sponsored the Acid Tests, a series of events based around the taking of LSD (supplied by Stanley), accompanied by light shows, film projection and discordant, improvised music known as the psychedelic symphony.[19] The Pranksters helped popularize LSD use through their road trips across America in a psychedelically-decorated school bus, which involved distributing the drug and meeting with major figures of the beat movement, and through publications about their activities such as Tom Wolfe's The Electric Kool-Aid Acid Test (1968).[21]

Leary was a well-known proponent of the use of psychedelics, as was Aldous Huxley. However, both advanced widely different opinions on the broad use of psychedelics by state and civil society. Leary promulgated the idea of such substances as a panacea, while Huxley suggested that only the cultural and intellectual elite should partake of entheogens systematically.[citation needed]

In the 1960s the use of psychedelic drugs became widespread in modern Western culture, particularly in the United States and Britain. The movement is credited to Michael Hollingshead who arrived in America from London in 1965. He was sent to the U.S. by other members of the psychedelic movement to get their ideas exposure.[22] The Summer of Love of 1967 and the resultant popularization of the hippie culture to the mainstream popularized psychedelia in the minds of popular culture, where it remained dominant through the 1970s.[citation needed]

The impact of psychedelic drugs on western culture in the 1960s led to semantic drift in the use of the word "psychedelic", and it is now frequently used to describe anything with abstract decoration of multiple bright colours, similar to those seen in drug-induced hallucinations. In objection to this new meaning, and to what some[who?] consider pejorative meanings of other synonyms such as "hallucinogen" and "psychotomimetic", the term "entheogen" was proposed and is seeing increasing use. However, many consider the term "entheogen" best reserved for religious and spiritual usage, such as certain Native American churches do with the peyote sacrament, and "psychedelic" left to describe those who are using these drugs for recreation, psychotherapy, physical healing, or creative problem solving. In science, hallucinogen remains the standard term.[23]

Advances in printing and photographic technology in the 1960s saw the traditional lithography printing techniques rapidly superseded by the offset printing system. This and other technical and industrial innovations gave young artists access to exciting new graphic techniques and media, including photographic and mixed media collage, metallic foils, and vivid new fluorescent "DayGlo" inks. This enabled them to explore innovative new illustrative styles including highly distorted visuals, cartoons, and lurid colors and full spectrums to evoke a sense of altered consciousness; many works also featured idiosyncratic and complex new fonts and lettering styles (most notably in the work of San Francisco-based poster artist Rick Griffin). Many artists in the late 1960s and early 1970s attempted to illustrate the psychedelic experience in paintings, drawings, illustrations, and other forms of graphic design. In the modern era, computer graphics may be used to produce psychedelic effects for artwork.[citation needed]

The counterculture music scene frequently used psychedelic designs on posters during the Summer of Love, leading to a popularization of the style. The most productive and influential centre of psychedelic art in the late 1960s was San Francisco; a scene driven in large measure by the patronage of the popular local music venues of the day like the Avalon Ballroom and Bill Graham's Fillmore West, which regularly commissioned young local artists like Robert Crumb, Stanley Mouse, Rick Griffin and others. They produced a wealth of distinctive psychedelic promotional posters and handbills for concerts that featured emerging psychedelic bands like Big Brother and the Holding Company, The Grateful Dead and Jefferson Airplane. Many of these works are now regarded as classics of the poster genre, and original items by these artists command high prices on the collector market today. Peter Max's psychedelic poster designs helped popularize brightly colored spectrums widely, especially among college students.[citation needed]

Contemporary with the burgeoning San Francisco scene, a smaller but equally creative psychedelic art movement emerged in London, led by expatriate Australian pop artist Martin Sharp, who created many striking psychedelic posters and illustrations for the influential underground publication Oz magazine, as well as the famous album covers for the Cream albums Disraeli Gears and Wheels of Fire. Other prominent London practitioners of the style included: design duo Hapshash and the Coloured Coat, whose work included numerous famous posters, as well as psychedelic "makeovers" on a piano for Paul McCartney and a car for doomed Guinness heir Tara Browne, and design collective The Fool, who created clothes and album art for several leading UK bands including The Beatles, Cream, and The Move. They painted psychedelic designs on musical instruments for John Lennon and Cream, created psychedelic murals for the Surrey home of Beatle George Harrison, and designed the famous psychedelic mural on the facade of the short-lived Apple Boutique in Baker St, London.[citation needed]

The trend also extended to motor vehicles. The earliest, and perhaps most famous of all psychedelic vehicles was the famous "Further" bus, driven by Ken Kesey and The Merry Pranksters, which was painted inside and out in 1964 with bold psychedelic designs (although these were executed in primary colours, since the DayGlo colours that soon became de rigueur were then not widely available). Another very famous example is the Rolls Royce owned by John Lennon - originally black, he had it repainted in 1967 in a vivid psychedelic gypsy caravan style, prompting bandmate George Harrison to have his Mini Cooper similarly repainted with logos and devices that reflected his burgeoning interest in Indian spirituality. Other notable examples include several cars re-painted in psychedelic style by Hapshash & The Coloured Coat and the famous psychedelic Porsche owned by American singer Janis Joplin.[citation needed]

The fashion for psychedelic drugs gave its name to the style of psychedelia, a term describing a category of rock music known as psychedelic rock, as well as visual art, fashion, and culture that is associated originally with the high 1960s, hippies, and the Haight-Ashbury neighborhood of San Francisco, California.[24] It often used new recording techniques and effects while drawing on Eastern sources such as the ragas and drones of Indian music.

One of the first uses of the word in the music scene of this time was in the 1964 recording of "Hesitation Blues" by folk group the Holy Modal Rounders.[25] The term was introduced to rock music and popularized by the 13th Floor Elevators 1966 album The Psychedelic Sounds of the 13th Floor Elevators.[25] Psychedelia truly took off in 1967 with the Summer of Love and, although associated with San Francisco, the style soon spread across the US, and worldwide.[26]

The counterculture of the 1960s had a strong influence on the popular culture of the early 1970s. It later became linked to a style of electronic dance music known as psychedelic trance.

A psychedelic festival is a gathering that promotes psychedelic music and art in an effort to unite participants in a communal psychedelic experience.[27] Psychedelic festivals have been described as "temporary communities reproduced via personal and collective acts of transgression...through the routine expenditure of excess energy, and through self-sacrifice in acts of abandonment involving ecstatic dancing often fuelled by chemical cocktails."[27] These festivals often emphasize the ideals of peace, love, unity, and respect.[27] Notable psychedelic festivals include the biennial Boom Festival in Portugal,[27] OZORA Festival in Hungary, Universo Paralello in Brazil as well as Nevada's Burning Man[28] and California's Symbiosis Gathering in the United States.[29]

In recent years there has been a resurgence in interest in psychedelic research and a growing number of conferences now take place across the globe.[30] The psychedelic research charity Breaking Convention have hosted one of the worlds largest since 2011. A biennial conference in London, UK, Breaking Convention: a multidisciplinary conference on psychedelic consciousness[31] is a multidisciplinary conference on psychedelic consciousness. In the US MAPS held their first Psychedelic Science conference,[32] devoted specifically to research of psychedelics in scientific and medical fields, in 2013.

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Psychedelia - Wikipedia

A Microdose Of “Magic Mushrooms” Could Unleash Your Creativity

Free Your Mind

It turns out you don’t have to risk a bad trip to enjoy the mind-expanding benefits of psychedelics.

According to researchers from Leiden University, just a tiny dose of magic mushrooms or truffles containing psychedelic substances — an amount unlikely to make you think the floor is alive and wants to eat you — can enhance your cognitive abilities.

With Free Drugs

For their study, which was published Thursday in the journal Psychopharmacology, the researchers first tracked down 36 volunteers at an event organized by the Psychedelic Society of The Netherlands.

Then they asked these volunteers to each complete three tasks, which they designed to assess the person’s ability to identify a solution to a problem (that’s called convergent thinking), reason and find answers to new problems (fluid intelligence), and recognize many possible solutions to a problem (divergent thinking).

Each volunteer completed the tasks twice: once before consuming approximately 0.37 grams of dried truffles — that’s about one-third the weight of a jelly bean — and once after.

The researchers found that the microdoses improved the volunteers’ divergent and convergent thinking — they were better equipped to find a single solution to a problem and conjure up additional out-of-the-box solutions.

Do Trip

Microdosing has gained popularity in recent years among tech workers who think it gives them a creative boost at work, but this was the first study to explore how microdosing psychedelic substances can affect a volunteer’s cognitive abilities in a natural setting. Lead researcher Luisa Prochazkova is hopeful that its results will inspire others to pursue similar research on magic mushrooms.

“Apart from its benefits as a potential cognitive enhancement technique, microdosing could be further investigated for its therapeutic efficacy to help individuals who suffer from rigid thought patterns or behavior such as individuals with depression or obsessive-compulsive disorder,” she said in a press release.

And those benefits would come without the potential side effect of a bad trip.

READ MORE: Can Tiny Doses of Magic Mushrooms Unlock Creativity? [EurekAlert]

More on psychedelics: Did an Acid Trip Change Your Life? Scientists Want to Know About It

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A Microdose Of “Magic Mushrooms” Could Unleash Your Creativity

Famous Users of Psychedelics – How to Use Psychedelics for …

Psychedelics have been used by many of the most creative and successful individuals in our society. Because of the stigma surrounding psychedelics, only a small percentage of these people have spoken publicly about their experiences. Here are a few who have. Right now, this list is just white men! We'd love to feature some well-known people of color and women-- please let us know if you have any suggestions.

Steve Jobs and his Apple co-Founder Steve Wozniak took LSD many times at the beginning of their career. Their experiences are discussed in Walter Isaacson's biography of Steve Jobs.

"Taking LSD was a profound experience, one of the most important things in my life. LSD shows you that there's another side to the coin, and you cant remember it when it wears off, but you know it. It reinforced my sense of what was importantcreating great things instead of making money, putting things back into the stream of history and of human consciousness as much as I could."

Steve JobsFounder, Apple

Susan Sarandon discussed ayahuasca and mushrooms in an interview with the Daily Beast.

"Ive done Ayahuasca and Ive done mushrooms and things like that. But I like those drugs in the outdoorsIm not a city-tripper... I like doing it in the Grand Canyon, or in the woods. You want to be prepared and not have responsibilities. It does remind you of your space in the universeyour place in the universeand reframe things for you. I think you can have some very profound experiences."

Susan SarandonActor

Frances McDormand described her experiences with LSD and psychedelic mushrooms in a 2014 interview with the Daily Beast.

"I really, really enjoyed LSD. And I really enjoyed mushrooms very much. Its unfortunate, I think, that drugs were not handled properly. Politically, theyve been used to separate the economic classes. Thankfully, its all getting fixed now with the marijuana laws. But with LSD, because it was countercultural, and because it was used as an experimental drug, it was not marketed properly. It if had been marketed properly, we would have it.... We needed a PR person for that LSD! It was very profound. Very profound."

Frances McDormandActor

Tim Ferriss is a multi-bestselling author of the Four-Hour Workweek and the Four-Hour Body. He has spoken repeatedly about his use of psychedelics and his advice about what he considers a safe and productive approach.

"The billionaires I know, almost without exception, use hallucinogens on a regular basis," Ferriss said. "[They're] trying to be very disruptive and look at the problems in the world ... and ask completely new questions." - Tim Ferris, CNN.com

In this video he addresses the subject in depth:

Cary Grant was used LSD with his therapist many times and was an advocate. Vanity Fair wrote about his experiences in detail in this article from 2010.

"The Curious Story Behind the New Cary Grant headlined the September 1, 1959, issue of Look magazine, and inside was a glowing account of how, because of LSD therapy, "at last, I am close to happiness." He later explained that "I wanted to rid myself of all my hypocrisies. I wanted to work through the events of my childhood, my relationship with my parents and my former wives. I did not want to spend years in analysis."

Vanity Fair

Kary Mullis won the Nobel Prize in Chemistry in for dramatically improving the technique of polymerase chain reaction (PCR), which is an essential tool of modern biology research. Albert Hofmann, the inventor of LSD, was told by Kary that LSD had helped him develop his PCR invention (Wired, 2008).

"Back in the 1960s and early '70s I took plenty of LSD. A lot of people were doing that in Berkeley back then. And I found it to be a mind-opening experience. It was certainly much more important than any courses I ever took."

Kary MullisCalifornia Monthly, 1994

"What if I had not taken LSD ever; would I have still invented PCR?" He replied, "I don't know. I doubt it. I seriously doubt it."

Kary MullisBBC Horizon Interview, 1997

Psychedelics have been misunderstood and misrepresented for decades. That's changing. Please help us share safe, responsible information on using psychedelics by sending this page to friends, and posting to Facebook, Twitter, and Google:

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Famous Users of Psychedelics - How to Use Psychedelics for ...

How to Use MDMA

MDMA is a truly remarkable medicine for working with difficult emotional experiences. The clinical results have far exceeded other interventions for a range of uses (see the research section at the bottom of this page).

MDMA is a synthetic psychedelic, first developed by the pharmaceutical company Merck in 1912. It has been widely studied since then, particularly for psychotherapeutic uses. With the rate of academic research growing rapidly, it is likely that MDMA will become FDA approved for therapeutic use within the next few years, and MAPS.org is focused on moving it through the approval process. MDMA is being widely tested for post-traumatic stress, with results that surpass any other existing treatment method.

MDMA is a particularly appealing psychedelic for therapists and researchers because the subjective mental experience feels fairly stable, while creating a dramatic increase in emotional openness and a reduction in fear and anxiety.

Before you begin, be sure to read our safety section and see the special safety considerations for MDMA at the bottom of this page.

Because MDMA has anti-anxiety and anti-fear effects, it is generally considered safe to use a full dose your first time and each time you use MDMA (generally 75mg - 125mg depending on the individual). It is important to measure the dose carefully. Milligram-precision scales cost about 20 dollars (heres an Amazon search for milligram scale).

Some therapy protocols add a booster dose of about 60mg of MDMA 2-3 hours after the first dose to extend the period of therapeutic effects and provide more time for deep exploration.

MDMA will typically be in the form of a powder, pill, or crystal. Again, be sure that you are receiving pure MDMA, not mixed with other drugs or stimulants like caffeine. 'Molly' is another term for pure MDMA, distinguished from 'Ecstasy' which often contains MDMA but is not pure MDMA. If the MDMA is in pill form, youll have to be confident of the reported dosage, as fillers are added to create a pill and weighing the pill will not indicate the MDMA content. As always, do not take any MDMA if you are unsure of quantity or purity.

Once the MDMA has worn off, be sure that you drink lots of water and get a long peaceful sleep at night. MDMA can be mentally tiring and you need to rejuvenate.

Most people find that they have an afterglow from their MDMA experience that can last days or weeks, improving their mood and outlook and keeping them very open to others.

On the other hand, some people feel mentally drained by MDMA and have a foggy headed feeling for a day or two afterwards. Others will feel emotionally drained, and have a depressed mood for up to a week after the experience. Sometimes, these feelings begin two days after the experience, but not the day after. To combat this, some people who feel sensitive to that after-effect will take 5-HTP or L-Tryptophan (both are common supplements available from any source) for a few days after MDMA in an attempt to restore their serotonin levels. People who do feel drained after an MDMA session generally report that precise the MDMA dose can affect how they feel afterwards. Too much may leave them more drained than necessary. This is another reason to start with a modest, precisely measured dose to begin.

Nearly everyone, no matter how they feel the following week, finds that the thoughts, feelings, and emotional release that they experience on MDMA persists afterwards. In particular, any realizations that they had during the experiences tend to prove real and lasting.

Most remarkably, painful emotional associations with life experiences -- traumas, breakups, divorces, etc -- are dramatically reduced if that issue has been explored during the experience. You will find that when you think about that same painful experience after exploring it on MDMA, you will not have the same flood of emotional pain and tension that you would have had beforehand. The memory will be intact but the emotional strings will be looser.

Even for extreme emotional trauma, this holds true. In a recent research study for patients with PTSD, 83% of patients experienced reduced symptoms after just 3 MDMA sessions combined with therapy, vs. only 25% of patients who had therapy alone. Quite simple, MDMA is the most effective treatment for PTSD ever developed. Compare this level of success to traditional anti-depressants which have strong side effects and are dosed every day for years at a time (for a total of hundreds or thousands of doses) and which have very low rates of effectiveness, often just slightly above placebo.

In addition to our standard safety suggestions, there are three particularly important precautions for MDMA use:

Psychedelics have been misunderstood and misrepresented for decades. That's changing. Please help us share safe, responsible information on using psychedelics by sending this page to friends, and posting to Facebook, Twitter, and Google:

Read more here:

How to Use MDMA

Psychedelics – PsychonautWiki

Psychedelics (also known as serotonergic hallucinogens) are a class of psychoactive substances that produce profound alterations in perception, mood and numerous cognitive processes.[1]

Psychedelics exert their effects primarily by binding to and activating the receptors for serotonin (5-hydroxytryptamine or 5-HT), particularly the 5-HT2a receptor. Serotonin plays a number of critical roles all throughout the human body and is a key neurotransmitter involved in the functioning and regulation of sensory perception, behavior, mood, cognition and memory.[2]

The term "psychedelic" was coined by the British psychiatrist Humphrey Osmond in 1956. It derives from the Greek words (psyche, "soul, mind") and (delein, "to manifest") which taken together mean "soul-manifesting," with the implication being that psychedelics can allow one to access the soul and develop unused potentials of the human mind.[3][4]

Unlike most highly prohibited substances, psychedelics are generally considered to be physiologically safe and non-addictive by the scientific community.[1]

The use of psychedelics predates written history, and they were employed by early cultures in many sociocultural and ritual contexts.[1] In modern times, psychedelic substances are used in a range of contexts spanning from the shamanic, religious and "spiritual", or the transpersonal. They are sometimes referred to as entheogens (i.e. "generating the divine within")[5] by those who use them for these purposes, although they are also used in purely recreational settings.

The term "psychedelic" was first coined in 1956 by psychiatrist Humphry Osmond as an alternative descriptor for hallucinogenic substances in the context of psychedelic psychotherapy.[6] Seeking a name for the experience induced by LSD, Osmond contacted Aldous Huxley, a personal acquaintance and advocate for the therapeutic use of the substance. Huxley coined the term "phanerothyme," from the Greek terms for "manifest" () and "spirit" (). In a letter to Osmond, he wrote:

To make this mundane world sublime,

To which Osmond responded:

To fathom Hell or soar angelic,Just take a pinch of psychedelic[7]

It was on this term that Osmond eventually settled, because it was "clear, euphonious and uncontaminated by other associations."[8] This mongrel spelling of the word 'psychedelic' was loathed by American ethnobotanist Richard Evans Schultes, but championed by Timothy Leary, who thought it sounded better.[9] Due to the expanded use of the term "psychedelic" in pop culture and a perceived incorrect verbal formulation, Carl A.P. Ruck, Jeremy Bigwood, Danny Staples, Jonathan Ott, and R. Gordon Wasson proposed the term "entheogen" to describe the religious or spiritual experience produced by such substances.[10]

Psychedelics act on serotonin receptors (also referred to as 5-HT receptors) via the way in which they act as full or partial agonists through their structural similarity to the serotonin molecule. It has a higher affinity than serotonin itself for the receptors, therefore preventing serotonin from binding to the receptors by competing with it.

While the method of action behind psychedelics is not fully understood, serotonergic psychedelics are known to show affinities for various 5-HT receptors and may be classified by their activity at different 5-HT subsites, such as 5-HT1A, 5-HT1B, 5-HT2A, etc.

Many serotonergic psychedelics share very close chemical and structural similarities to serotonin itself. There is a consensus that serotonergic psychedelics produce their effects by acting as uniquely effective partial agonists at 5-HT2A receptor sites.[14]

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

The "classical psychedelics" are all classed as serotonergic in nature.[14] This means that they structurally mimic the endogenous neurotransmitter known as serotonin, the neurotransmitter that regulates higher-level brain functions such as mood, sensory perception, cognition, and memory.[2]

The diagram to the right shows the structural similarities and differences between the various classes of psychedelics and the serotonin neurotransmitter.The three classes (phenethylamines, lysergamides and tryptamines) all contain the same chemical rings (which have been labeled).

Psychedelics are considered to be non-addictive, do not cause brain damage, and tend to have an extremely low toxicity relative to dose.[1]

Most psychedelics have very few physical side effects associated with acute exposure. Various studies have shown that in reasonable doses in a sufficiently prepared context, they are very unlike to present negative physical, cognitive, psychiatric or other toxic consequences. There is no evidence that any psychedelics causes damage to any human body organ.[17]

However, they can act as a potential trigger for those with underlying psychiatric conditions, so those with a family history of mental illness are generally advised not to use these substances.

Psychedelics do not have established lethal dosages. There are no well-documented deaths attributable to the direct pharmacological action of any psychedelic, with the notable exception of the 25x-NBOMe series.

Psychedelics are not habit-forming and the desire to use them can actually decrease with use. They are generally considered to be self-regulating aspect, although cases of dependence and addiction have been recorded.[Controversial] Notably, there is virtually no withdrawal syndrome when the chronic use of these substances have ceased.[18]

Although many psychoactive substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

The information below describes and explains various concepts regarding the responsible use of psychedelic substances. These should be read over and carefully considered before one decides whether or not the potential benefits of experimenting with psychedelics outweighs the potential risks.

One of the most important factors to consider as an inexperienced user is one's current state of mind. Many substances exponentially enhance a person's current state of mind, emotions and general perspective on the world which is a process that can go in either a positive and euphoric direction or a negative, terrifying and anxiety ridden direction. It is because of this that many substances should not be used by the inexperienced during stressful or negative periods of life and users should be fully aware of the ways in which hallucinogens and other drugs, particularly psychedelics, consistently force a person to face and deal with their personal introspective problems that all human beings deal with.

It has often been recommended that those with severe pre-existing mental conditions (especially individuals with psychotic illnesses like schizophrenia) should not ingest these substances due to the way they strongly increase one's current state of mind and emotions as well as cause delusions and hallucinations.

Throughout the experience itself the person needs to let go and allow the effects to take charge. One should be taking the metaphorical passenger seat and never trying to control any part of the experience. It is extremely important that people simply relax and take things as they come. The user must understand that the act of tripping is often ineffable and incomprehensible at high enough dosages, meaning that an acceptance of not being able to understand the full scope of what is happening should be present at all times. One should be embracing the fact that their thought processes, although more insightful in places, will be inherently impaired along with motor control, conversational skills and general functioning. The user should be sure to view these effects as normal and not feel self-conscious or insecure about them within the presence of others.

If one is using hallucinogens, a sober, responsible trip sitter is strongly recommended to be present throughout a trip by an inexperienced individual or group with an unfamiliar substance. It is this persons responsibility to assist the individual or group by maintaining a rational and responsible frame of mind. This should be done by simply watching over the trippers and calmly reassuring them if they experience any anxiety or stress, whilst also preventing them from coming to any harm. There is an obvious correlation between the name trip sitter and babysitter; this is because at many times, trip sitting can be like babysitting and it is definitely a responsibility that must be taken just as seriously.

A good trip sitter needs to be sure of a number of things throughout the experience. They should remain (mostly) sober and should be able to empathize with the group members situation through personal experiences with the substance/similar substances or at least a considerable amount of research on their effects. Trip sitters should understand that when a person is tripping, they might not be able to communicate as they usually do. Also, their balance and spatial judgement may be off so assistance in performing physical tasks such as keeping hydrated can greatly reduce anxiety. The trip sitter can contribute to the conversation, but should also remember to leave them to explore the experience without too much external influence.

Once a person is familiar with the experience, it becomes down to them whether or not they feel comfortable enough to trip without a sitter.

An anchor, in the context of hallucinogen usage, can be defined as an activity or physical object which keeps one grounded during heavy suppression and distortion of a person's sense of time, space, language, ego and short/long-term memory. At higher dosages, this can result in extreme disorientation and confusion. Anchors are often used to counteract this and maintain one's concept of the current situation as it is within reality. Examples of anchors include:

Hallucinogens have the potential to become overwhelming and push trippers into paranoid/dreadful moods if the tripper is inexperienced or in an inappropriate setting.

If one decides that they want the trip to end, benzodiazepines and other sedatives such as some antipsychotics can be considered as an analogous "eject button" of a downhill-headed or extensively long trip. They are very useful tools in preventing panic attacks, paranoia, and possible traumatic experiences. If these are available, be sure to keep them at hand as they are extremely effective tools for mitigating a hallucinogenic crisis. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Read more:

Psychedelics - PsychonautWiki

Microdosing: The Revolutionary Way of Using Psychedelics …

Microdosing of 10 to 20 micrograms (of LSD)allow me to increase my focus, open my heart, and achieve breakthrough results while remaining integrated within my routine. My wit, response time, and visual and mental acuity seem greater than normal on it.

Madeline, The Psychedelic Explorers Guide

On a beautiful morning in Amsterdam I grabbed my vial of LSD, diluted down with half high grade vodka and half distilled water, and told my friend to trust me and open his mouth. While semi-carefully measuring the droplets for his microdose, I told him to whirl it around in his mouth for a few minutes before swallowing the neuro-chemical concoction. I quickly followed suit.

We had one of the best walking conversation ofour lives.

I first became immenselycurious about the potential of microdosing psychedelics after reading this captivating storyabout James Fadiman and his research. After a few test-runs, I knew I stumbled upon something significant.

Today we arewitnessing the birth of a truly remarkable epoch. With the psychedelic renaissance well under way, consisting ofnew fascinating research, the coming out of thousands of individuals and the introduction of many, hitherto unknown, psychoactive plants steeped in their cultural context of healing and initiation, we are now facing some new and interesting questions.

I think one of the more fruitful directions we can take is towards is microdosing.

Microdosing is taking sub-perceptual doses (6-25 microgram LSD, 0.2-0.5 gram dried mushrooms, 50-75 microgram mescaline HCL) while keeping up with ones daily activities, engaging in extreme sports, appreciating nature or enhancing ones spiritual practice.

This manner of integrating psychedelics, also known as a psycholytic dose, doesnt inhibit ego-functioning in the same intense manner asthe heroic Terence McKennadose does. It is much easier integrated into non-psychedelic activities.

It is knownthat Albert Hofmann, the first synthesizer of LSD, continued this practice well into his old age while saying it would have gone on to be used as Ritalin if it hadnt been so harshly scheduled.

James Oroc, the author of the amazing book Tryptamine Palace: 5-MeO-DMT and the Sonoran Desert Toad, while writing about the secret affair between psychedelics and extreme sports, saysthat taking psychedelics at lower doses, the cognitive functioning, emotional balance, and physical stamina were actually found to be improved.

For some, this might not come as a surprise, since Hofmann already spoke in a now famous interview that Lysergic acid diethyl amide (LSD) is related in chemical structure to nicotinic acid diethylamide, known to be an effective analeptic. (central nervous stimulant.)

But theres more, as James Oroc eloquently put,

Virtually all athletes who learn to use LSD at psycholytic dosages believe that the use of these compounds improves both their stamina and their abilities. According to the combined reports of 40 years of use by the extreme sports underground, LSD can increase your re- flex time to lightning speed, improve your balance to the point of perfection, increase your concentration until you experience tunnel vision, and make you impervious to weakness or pain. LSDs effects in these regards amongst the extreme-sport community are in fact legendary, universal, and without dispute.

He goes so far to suggest that, to some in the extreme sports subculture, taking a microdose at any physical competition is considered cheating. And this is not just the case for sports.P.G. Stafford and B.H. Golightly write in LSD The Problem-Solving Psychedelicabout a student that wanted to learn german making huge strides under the influenceof an unknown amount of LSD.These are the words of the student:

It was a week before registration and it depressed me tremendously that I had not spent the summer learning German, as I had planned. I had intended to give myself a crash course so I could take second-year German, which I needed for my study in physics. I had heard of a woman who had learned enough Spanish in a few days, via LSD, to speak it fluently when she had to go to Mexico on business.

I had taken LSD before, and while I couldnt see how she did this, I decided it was worth a try. I hadnt even gotten around to picking up a textbook, but I did have a close friend who knew German well and who said he was willing to sit in while I took the drug and try to teach me the language.

Fortunately, I knew something about conjugation and declension, so I wasnt completely at sea. I wanted to get worked up and feel involved with the language, as it seemed that this must be at least part of the key to the problem, so I asked my friend to tell me about Schiller and Goethe, and why the verb came at the end. Almost immediately, after just a story or two, I knew I had been missing a lot in ignoring the Germans, and I really got excited. The thing that impressed me at first was the delicacy of the language (he was now giving me some simple words and phrases), and though I really messed it up, I was trying hard to imitate his pronunciation as I had never tried to mimic anything before.

For most people German may be guttural, but for me it was light and lacey. Before long, I was catching on even to the umlauts. Things were speeding up like mad, and there were floods of associations. My friend had only to give me a German word, and almost immediately I knew what it was through cognates. It turned out that it wasnt even necessary for him to ask me what it sounded like.

Memory, of course, is a matter of association, and boy, was I ever linking up to things! I had no difficulty recalling words he had given mein fact, I was eager to string them together. In a couple of hours after that I was reading even some simple German, and it all made sense.

The whole experience was an explosion of discoveries. Normally, when youve been working on something for a long time and finally discover a solution, you get excited, and you can see implications everywhere. Much more than if you heard someone else discovering the same-thing. Now this discovery thing, thats what was happening with mebut all the time.

The threshold of understanding was extremely low, so that with every new phrase I felt I was making major discoveries. When I was reading, it was as though I had discovered the Rosetta Stone and the world was waiting for my translation. Really wild!

In the 60s the creativity enhancing effects of psychedelics were already hailed as revolutionary, and these famous tripperswould certainly agree. One significant study investigated the effect of 100 micrograms of LSD on top of the field experts who had been struggling with a hard problem for months. Their solutions were reviewed by a panel of other experts in the same field. As Tim Doody reports;

LSD absolutely had helped them solve their complex, seemingly intractable problems. And the establishment agreed. The 26 men unleashed a slew of widely embraced innovations shortly after their LSD experiences, including a mathematical theorem for NOR gate circuits, a conceptual model of a photon, a linear electron accelerator beam-steering device, a new design for the vibratory microtome, a technical improvement of the magnetic tape recorder, blueprints for a private residency and an arts-and-crafts shopping plaza, and a space probe experiment designed to measure solar properties.

Psychedelics can be described as non-specific amplifiers, and, as such, not just creativity can be enhanced, also the distressing states of mind. In smaller doses this is not as overwhelming and therefore, if used properly, can be quite beneficial.

Myron Stolaroff, while writing about the usefulness of psychedelics in the practice of buddhism, argues that low doses of psychedelics can be extremely beneficial to improve ones meditation practice.

The use of low doses often can be much more effective in dealing with our psychic garbage. Many do not care for low doses because they can stir up uncomfortable feelings, and they prefer to transcend them by pushing on into higher states, but it is precisely these uncomfortable feelings that must be resolved to achieve true freedom.

With low doses, by focusing directly on the feelings and staying with them without aversion and without grasping, they will in time dissipate. Resolving ones repressed feelings in this manner clears the inner being, permitting the True Self to manifest more steadily. Such a result provides greater energy, deeper peace, more perceptive awareness, greater clarity, keener intuition, and greater compassion. It permits the deepening of ones meditation practice. The surfacing of buried feelings that this procedure permits often can bring new understanding of ones personality dynamics.

The potential to improve cognitive functioning, body awareness and our spiritual evolution with a microdose of psychedelics are limitless. There are five categories by which we can describe the overall effects of microdosing LSD. I gathered these from the various first person reports Ive quoted so far and my own extensive experimentation.

To be able to experiment with these states of conscious in a safe and constructive manner, be sure to follow these guidelines.

To make this trivial world sublime, take half a gram of phanerothyme -Huxley

In a not so far away future it will be possible to unlock different experiences with a pill. A little piece of matter, folded and turned using organic chemistry into a unique organic key to insert your brain. A drug you can buy as easy as alcohol or tobacco, or weed. Perhaps it will thrive in a system where one has to take an exam, some basic tests, and will be rewarded a license of some kind.

Aldous Huxley envisionedin Island,his last, and according to himself, his most important book, that psychedelics could help us overcome addiction, anxiety and depression. That if we could change how we experience ourselves, our loved ones and the world at large, either through rituals or through neurochemical mediated ways, we could usher in a new paradigm of human flourishing.

While his vision has not come to fruition yet, it is still very much alive. With the practice of microdosing, we will be one step closer to learning how to cope with the vast depths of our own psyches.

Enjoy the magic, my friends.

Share your microdose experience here

Ive gotten so many questions, requests and microdose stories after writing this article that I have decided to write an e-book on this fascinating subject matter. If youd like to help, I am looking for:

All information received will be used anonymously. Please enter Microdosing as the subject. Thank you 🙂

As we repeatedly stress on HighExistence, psychedelics mustbe approached with reverence and caution. We believe that in a loving context, psychedelics are powerful medicines with tremendous potential, but there are a number of physical and psychological safety concerns that one should consider before journeying with psychedelics. Please, please do plenty of research, and do not take psychedelics if you have reason to believe that they will not jibe with your personality or particular mental baggage.The Essential Psychedelic Guideon Erowid is an exceptional free resource, and we recommend reading it,especiallythe section on Psychedelic Safety, before ever dabbling in these substances. Take care, and happy tripping. : )

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Microdosing: The Revolutionary Way of Using Psychedelics ...

The Truth About What Psychedelics Do to Your Brain


Tom McKay, PolicyMicWaking Times

Scientists Studied What Psychedelics Do to the Brain, and Its Not What Youve Been Told

It turns out that psychedelics arent just good forturning into an elf and jousting a car. Psychiatrists, psychologists and specialists in addiction and recovery from traumatic experiences have been investigating the use of hallucinogens in treatment programs, and the results indicate that psychedelics actually have practical therapeutic uses. And one drug has proven particularly useful.Repeated studies have found the psychedelic compound found in magic mushrooms, psilocybin, can help people move past major life issues like beating alcoholism and becoming more empathetic.

The research:One study concluded that controlled exposure to psilocybin could havelong-lasting medical and spiritual benefits. In 2011,Johns Hopkins researchers found that by giving volunteer test subjects just the right dose (not enough to give them a terrifying bad trip), they were able to reliably induce transcendental experiences in volunteers. This provoked long-lasting psychological growth and helped the volunteers to find peace in their lives, all without side effects. Nearly all of the 18 test subjects, average age 46, were college graduates. Seventy-eight percent were religious and all were interested in finding a scientific experience.

Fourteen months later, 94% said their trip on magic mushrooms was one of the five most important moments of their lives. Thirty-nine percent said it was the most important thing that had ever happened to them. Their colleagues, friends, and family members said the participants were kinder and happier; the volunteers had positive experiences ranging from more empathy and improved marriages to less drinking.Lead author Roland Griffithstold TIMEsHealthlandthat The important point here is that we found the sweet spot where we can optimize the positive persistent effects and avoid some of the fear and anxiety that can occur and can be quite disruptive.

Whats more, the researchers say that those changes in personality are highly atypical, because personalities tend to be pretty set in stone after the age of 25-30.Accordingto postdoctoral researcher Katherine MacLean, who contributed to the study, This is one of the first studies to show that you actually can change adult personality.

Many years later, people are saying it was one of the most profound experiences of their life, she continued. If you think about it in that context, its not that surprising that it might be permanent.

This is strictly do-not-try-this-at-home. Macleansaysthat in an unsupervised setting, if that sort of fear or anxiety set in, the classic bad trip, it could be pretty dangerous. But On the most speculative side, this suggests that there might be an application of psilocybin for creativity or more intellectual outcomes that we really havent explored at all.

More research:Within the past few decades, interest in hallucinogens has expanded from the counter-culture to dedicated, methodological research. For example,another study published in 2010conducted research into whether psilocybin can lend some comfort to terminal cancer patients finding evidence that it reduced death anxiety and experienced significantly less depression.Accordingto study researcher Dr. Charles Grob, Individuals did speak up and tell us that they felt it was of great value. NYUs Dr. Stephen Ross, who conducted a similar study,told SCPRthat To me its been some of the most remarkable clinical findings Ive ever seen as a psychiatrist.

Psychologist Clark Martin, Ph.D., who participated in the study as a volunteer, describes his experience below:

As well as participant Janeen Delaney:

As a result of the studies, a jointUCLA, NYU and Johns Hopkins team is conducting large-scale phase three trial next year.

Cluster headache patients say (with the backing of some doctors) that psilocybin and LSD provide them withsignificant relief, which researchers argue need further study.

A 2012 study published in theBritish Journal of Psychiatryfound evidencethat psilocybin enhances autobiographical recollection, suggesting psychiatric uses in the recall of salient memories or to reverse negative cognitive biases. Areviewof the pyschiatric research performed on psilocybin concluded that the risks of therapy were acceptable and that most subjects described the experience as pleasurable, enriching and non-threatening. And this year, Zrichresearchersreleased a studyin which they administered psilocybin to 25 volunteers. The treatment was found to be associated with an increase of positive mood in healthy volunteers.

So basically, theres at least some hard evidence that this:

Has the potential to be helpful, leading to introspection, self-reflection, and relief from psychiatric conditions.

Other drugs:Other illegal drugs have been linked to positive psychological outcomes. Trials with MDMA have hadpositive resultsin patients suffering from PTSD.Multidisciplinary Association for Psychedelic Studies founder Rick Doblin, who works with Iraq and Afghanistan veterans, discusses why MDMA might be the first psychedelic to open the door into traditional psychiatry and psychology:

So why isnt there more evidence?The federal government is only now beginning to loosen its restrictions on medical uses of mind-altering substances, and its doing so very cautiously. In 2013, a group of psychiatristsreleaseda review saying government restrictions made even researching psychoactive drugs difficult and in many cases almost impossible.

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The Truth About What Psychedelics Do to Your Brain was last modified: June 18th, 2016 by WakingTimes

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The Truth About What Psychedelics Do to Your Brain

Do Psychedelics Carry A Heart Risk? – The Third Wave

Microdosing is an exciting new prospect for the psychedelic community; what better way to incorporate the healing and mind-expanding benefits of psychedelics into our everyday lives? But with any change in lifestyle comes risk and psychedelics are relatively poorly understood in terms of what they do to our bodies. Although it appears that relatively infrequent, even large doses of psychedelics dont do much harm to healthy individuals, we dont have any evidence that regular microdosing is safe. There are reports of people microdosing for many months in succession, with no ill effects aside from tiredness but there is always the chance that with longer term microdosing regimens, unwanted physiological side effects could start building up.

One thing thats of some concern is the risk of heart disease. MDMA has been the centre of attention in this respect various studies have shown that there is alink between regular, high-dose MDMA use and heart defects. Although the conclusion of this research is that the occasional dose of MDMA will not harm you, it has potential implications for long-term psychedelic use, including microdosing.

MDMAs harmful effects on the heart are due to itsactivation of the 5-HT2B receptor. This receptor is present all over the heart, andconvincing evidence suggeststhat the long-term activation of this receptor leads to the formation of valvular strands, which can lead to Valvular Heart Disease (VHD) in extreme cases.

Again cases of VHD are only found in people who use MDMA very frequently (several times a week) and at high doses. The question we want to answer is: do the classic psychedelics (LSD and psilocybin) that we microdose with also activate the 5-HT2B receptor on our hearts, and is there a risk of VHD with long-term microdosing?

LSD and psilocybin work by mimicking the effect of our natural neurotransmitter, serotonin. Therefore both these psychedelics activate a wide range of serotonin receptors, including the 5-HT2B receptor. The real question is, are these psychedelics activating the 5-HT2B receptor enough to cause damage to the heart?

Unfortunately, we dont have an answer to that question. We know that LSD and psilocybinbind strongly to the 5-HT2B receptor, but we dont know how comparable this is to the way that MDMA (and other cardiotoxic molecules) binds to 5-HT2B. So right now, there is no way of knowing for sure if there is any risk.

We can, however, make some educated speculation.

We can look at a previous study of a compound that definitely causes heart damage through the 5-HT2B receptor: fenfluramine. This was a weight-loss drug that was withdrawn in the 90s after a small percentage of people developed heart disease after using it.

Studies found that fenfluramine roughly doubled the risk of developing VHD after a 90-day treatment course, at a dose of around 30mg/day (Sachdev et al, 2002). Fenfluramine has an affinity (Ki) for the 5-HT2B receptor of around 30nM (Rothman & Baumann, 2009).

LSD has a similar affinity for the 5-HT2B receptor as fenfluramine, a Ki of around 30nM (Passie et al, 2008). A typical microdosing regimen involves taking much less LSD than 30mg/day (actually the equivalent of3ug/day, several thousand times less than fenfluramine).

The comparison to fenfluramine isnt great its quitepossible that a daily dose of fenfluramine (rather than a dose every three days when microdosing) affects the 5-HT2B receptor differently. Additionally,we dont know to what extent LSD is activatingthe 5-HT2B receptors of the heart in comparison to fenfluramine. However, it seems reasonable to assume that microdosing has nowhere near the heart risk associated with fenfluramine.

Although there have been no long-term studies of the risk of microdosing in humans,one studygave 10ug/kg of psilocin to ratsevery otherday for several weeks.The findings of this study are unconvincing, to put it mildly, and it doesnt really tell us anything about the heart risks of microdosing.

Overall, we dont yet know anything for sure. Microdosing needs tobe studied in more detail and looking at the scarce evidence we have, its hard to draw any conclusions about the relative safety of microdosing.

While we believe that short-term microdosing is relatively safe, what remains to be seen is whether long-term microdosing regimens (i.e. for many months or even years) have a potential to damage the heart. This is why we advise to microdose for no longer than 90 days, and spread out your microdosing regimens throughout the year. If you have a pre-existing heart condition, it is especially important to avoid extended periods of microdosing.

We think that the potential heart risk of psychedelics actually highlights the need for their legalization. Without legalization, people will probably continue taking psychedelics without considering the risks, and as the popularity of microdosing increases, we might see more negative side effects.

But if psychedelics are legalized, we couldsee companies vying to produce psychedelic analogues that have beneficial psychological effects, without being damaging to our bodies in long-term use. Imaginea psychedelic designed specifically for microdosing; one that boosts our creativity and awareness, but doesnt damage our heart or other tissues.

The answer could be a psychedelic that only becomes active when it crosses into the brain; or a psychedelic that does not activate the 5-HT2B receptor in the heart. Perhaps we could even co-administer psychedelics with drugs that totally block the 5-HT2B receptor. To develop these ideal drugs, we first need legalisation, and for policymakers to accept that psychedelics will never leave our culture.

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Do Psychedelics Carry A Heart Risk? - The Third Wave