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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 (

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.,

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

Psychedelics – Mushrooms, LSD, Salvia

Psychedelics, while they can cause pleasurable side effects, are mostly Schedule I classified drugs that are not only illegal but dangerous. While psychedelics can cause a person to feel a sense of oneness with the universe and experience spiritual or enjoyable hallucinations and distorted perceptions, they can also cause intense fear, paranoia, and panic.

Whether or not a person has a good trip or a bad tripall depends on many variables, and there is no assurance that even the same individual will experience a positive reaction twice. This is only one of the dangers of psychedelics which, while they have been used in spiritual rituals for centuries, can cause many harmful effects.

We can help you quit using psychedelic drugs. Call 800-895-1695 today.

The effects of psychedelics are extremely hard to predict. As stated by CESAR, psilocybin or psychedelic mushrooms are one of the most popularly abused psychedelics to this day, and the effects produced by psilocybin are highly variable and depend on several factors including the age, type, and dosage amount of the mushroom used, the setting the mushroom is used in, the users expectations, past drug experiences, and personality.

This is what makes psychedelic drugs so different from other commonly abused substances; it is very difficult to pinpoint how a person will react to these drugs or what they should even expect. While some effects like hallucinations, nausea, and an altered perception of space and time can all be expected to be experienced by the user, psychedelics may cause a different type of high in every user (each and every time) and their effects could last anywhere from an hour to six or more.

While there isnt a strong amount of research on the issue of psychedelic drug addiction, it is possible in some instances. Especially with a drug like MDMA, some users report symptoms of dependence, including continued use despite knowledge of physical or psychological harm, tolerance (or diminished response), and withdrawal effects (NIDA).

Some other drugs (like LSDand peyote) only cause tolerance while the effects of salvia divinorum have not yet been researched enough to provide any conclusive results. The question of whether or not addiction to certain psychedelic drugs exists can be puzzling. In many cases, though, treatment may still be necessary to help with the effects abusing psychedelic drugs can cause.We can help you find the treatment you need. Call 800-895-1695 toll free today.

If you are concerned about your psychedelic drug abuse or that of another individual, here are some steps to follow in order to better the situation.

See the rest here:

Psychedelics – Mushrooms, LSD, Salvia

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. Studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction.[4]

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.

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.[5][6]

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.[7] 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.[8]

Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme (Greek “phaneroein-” visible + Greek “thymos” soul, thus “visible soul”).[9] 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.[10] 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.[11]

Almost all antidepressant drugs, especially atypical ones like mirtazapine and trazodone, are 5-HT2A antagonists, from moderate to very strong, and thus often totally disrupts psychedelic effects. Furthermore, persons on chronic antidepressive medications virtually can’t get any effects from serotonergic psychedelic drugs even after discontinuing antidepressant drugs.[citation needed]

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.[12] 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.[13]

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[14] and there being no evidence to support long term harm on mental health[15] 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.

See the original post here:

Psychedelic drug – Wikipedia

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. Studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction.[4]

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.

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.[5][6]

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.[7] 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.[8]

Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme (Greek “phaneroein-” visible + Greek “thymos” soul, thus “visible soul”).[9] 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.[10] 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.[11]

Almost all antidepressant drugs, especially atypical ones like mirtazapine and trazodone, are 5-HT2A antagonists, from moderate to very strong, and thus often totally disrupts psychedelic effects. Furthermore, persons on chronic antidepressive medications virtually can’t get any effects from serotonergic psychedelic drugs even after discontinuing antidepressant drugs.[citation needed]

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.[12] 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.[13]

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[14] and there being no evidence to support long term harm on mental health[15] 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.

View post:

Psychedelic drug – Wikipedia

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:

Problem-solving

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.

Creativity

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.

Mood

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.

Physical

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.

Original post:

Beginners Guide to Microdosing Psychedelics

Sacred Knowledge: Psychedelics and Religious Experiences …

Sacred Knowledge is the first well-documented, sophisticated account of the effect of psychedelics on biological processes, human consciousness, and revelatory religious experiences. Based on nearly three decades of legal research with volunteers, William A. Richards argues that, if used responsibly and legally, psychedelics have the potential to assuage suffering and constructively affect the …

See the article here:

Sacred Knowledge: Psychedelics and Religious Experiences …

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

See original here:

A Microdose Of “Magic Mushrooms” Could Unleash Your Creativity

Psychedelics – Mushrooms, LSD, Salvia

Psychedelics, while they can cause pleasurable side effects, are mostly Schedule I classified drugs that are not only illegal but dangerous. While psychedelics can cause a person to feel a sense of oneness with the universe and experience spiritual or enjoyable hallucinations and distorted perceptions, they can also cause intense fear, paranoia, and panic.

Whether or not a person has a good trip or a bad tripall depends on many variables, and there is no assurance that even the same individual will experience a positive reaction twice. This is only one of the dangers of psychedelics which, while they have been used in spiritual rituals for centuries, can cause many harmful effects.

We can help you quit using psychedelic drugs. Call 800-895-1695 today.

The effects of psychedelics are extremely hard to predict. As stated by CESAR, psilocybin or psychedelic mushrooms are one of the most popularly abused psychedelics to this day, and the effects produced by psilocybin are highly variable and depend on several factors including the age, type, and dosage amount of the mushroom used, the setting the mushroom is used in, the users expectations, past drug experiences, and personality.

This is what makes psychedelic drugs so different from other commonly abused substances; it is very difficult to pinpoint how a person will react to these drugs or what they should even expect. While some effects like hallucinations, nausea, and an altered perception of space and time can all be expected to be experienced by the user, psychedelics may cause a different type of high in every user (each and every time) and their effects could last anywhere from an hour to six or more.

While there isnt a strong amount of research on the issue of psychedelic drug addiction, it is possible in some instances. Especially with a drug like MDMA, some users report symptoms of dependence, including continued use despite knowledge of physical or psychological harm, tolerance (or diminished response), and withdrawal effects (NIDA).

Some other drugs (like LSDand peyote) only cause tolerance while the effects of salvia divinorum have not yet been researched enough to provide any conclusive results. The question of whether or not addiction to certain psychedelic drugs exists can be puzzling. In many cases, though, treatment may still be necessary to help with the effects abusing psychedelic drugs can cause.We can help you find the treatment you need. Call 800-895-1695 toll free today.

If you are concerned about your psychedelic drug abuse or that of another individual, here are some steps to follow in order to better the situation.

See the article here:

Psychedelics – Mushrooms, LSD, Salvia

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:

Problem-solving

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.

Creativity

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.

Mood

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.

Physical

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.

Read the rest here:

Beginners Guide to Microdosing Psychedelics

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. Studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction.[4]

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.

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.[5][6]

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.[7] 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.[8]

Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme (Greek “phaneroein-” visible + Greek “thymos” soul, thus “visible soul”).[9] 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).

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.[10] 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.[11]

Almost all antidepressant drugs, especially atypical ones like mirtazapine and trazodone, are 5-HT2A antagonists, from moderate to very strong, and thus often totally disrupts psychedelic effects. Furthermore, persons on chronic antidepressive medications virtually can’t get any effects from serotonergic psychedelic drugs even after discontinuing antidepressant drugs.[citation needed]

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.[12] 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.[13]

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[14] and there being no evidence to support long term harm on mental health[15] 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.

Read more:

Psychedelic drug – Wikipedia

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:

Problem-solving

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.

Creativity

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.

Mood

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.

Physical

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.

Read more:

Beginners Guide to Microdosing Psychedelics

Sacred Knowledge: Psychedelics and Religious Experiences …

Sacred Knowledge is not only timely and relevant to a whole host of current social/legal issues but also addresses, with seemingly effortless ease, many of the deeper/subtler metaphysical implications of psychedelicstheir therapeutic and spiritual potential. Richards’s clear prose makes articulating such difficult topics look easy. (G. William Barnard, Southern Methodist University)

Richards’ Sacred Knowledge is not a tome but rather a concise work rich with personal stories, observations, and insights into a compelling topic long ignored and now garnering the attention it has long deserved. (Charles S. Grob, University of California, Los Angeles, School of Medicine)

A seminal work that will become required reading for anyone seriously interested in either religious experience or psychedelic research. There has not been a book in this area as valuable since William James’s The Varieties of Religious Experience, more than a century ago. (James Fadiman, author of The Psychedelic Explorer’s Guide: Safe, Therapeutic, and Sacred Journeys)

In this wonderfully sensitive, critical, and confessional history one of the foremost clinicians and scholars of presents his own experience with psychedelics and with guiding others in studies to occasion mystical experiences using entheogens. Neither addictive nor toxic, these drugs whatever called surely can under the right set and setting reveal the God within us all. This book is the best accessible overview by someone who knows by experience, and can guide others whether they choose to be involved with entheogens personally or seek to simply to understand others who do. Regardless of choice, this loving man should be your guide. (Ralph W. Hood Jr. , University of Tennessee)

An inspiring testament to half a century of scientific research and personal exploration into the responsible, beneficial use of psychedelic substances. William A. Richards’s work is visionary, personal, and transpersonal, instilled with kindness, deep humanity, and quiet wisdom. (Don Lattin, author of The Harvard Psychedelic Club)

This is a great book which I highly recommend. It is an immersive experience, which provides an opportunity for those unfamiliar with nonordinary states of consciousness to catch a glimpse of their beauty and power. William A. Richards seamlessly weaves together his extensive understanding of spirituality on the one hand and academic and clinical science on the other a rare combination. His humour, insights, and empathy shine through on every page. The topic is timely and a manifestation of the fact that the intellectual battle regarding the potential of nonordinary states of consciousness (as, in this case, facilitated by psychedelics) has been won. (Amanda Feilding, director, Beckley Foundation)

Sacred Knowledge provides the most comprehensive overview of the actual use of psychedelics in psychotherapy and of the transformative power of mystical experiences. (Torsten Passie, Hannover Medical School)

This is a wonderful book and couldn’t have been launched at a more auspicious time. As William A. Richards has portrayed so beautifully, psychedelics provide an experience of total sanity and give a glimpse of a deeper, more heart-centred, and universal spiritual reality. In my opinion everyone should read this book, not just researchers, theologians, and philosophers but also the ordinary person in society. As society becomes more and more degraded, the planet more and more polluted, and the natural world destroyed, the truth of what the great mystic Krishnamurthy said, ‘It is no measure of health to be well adjusted to a profoundly sick society,’ will become ever more apparent. Increasingly I find more and more people are asking at a deeper level ‘why am I here? ‘What is this life about? What is it all for’? The sane answer to many of these questions is to be found in this book. (Ivor Browne, University College Dublin)

A practitioner and professor, Richards writes as a guide into the depths of psychedelic spirituality in an attempt to bring entheogenssubstances that ‘generate the divine within’back into the mainstream. (Publishers Weekly)

Richards is a generous and gregarious writer, who avoids platitudes for a mix of hard evidence, anecdotal stories, and memoir-like ruminations… Timely. (Baltimore City Paper)

Go here to see the original:

Sacred Knowledge: Psychedelics and Religious Experiences …

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. Studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction.[4]

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.

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.[5][6]

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.[7] 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.[8]

Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme (Greek “phaneroein-” visible + Greek “thymos” soul, thus “visible soul”).[9] 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).

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.[10] 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.[11]

Almost all antidepressant drugs, especially atypical ones like mirtazapine and trazodone, are 5-HT2A antagonists, from moderate to very strong, and thus often totally disrupts psychedelic effects. Furthermore, persons on chronic antidepressive medications virtually can’t get any effects from serotonergic psychedelic drugs even after discontinuing antidepressant drugs.[citation needed]

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.[12] 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.[13]

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[14] and there being no evidence to support long term harm on mental health[15] 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.

Original post:

Psychedelic drug – Wikipedia

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. Studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction.[4]

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.

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.[5][6]

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.[7] 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.[8]

Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme (Greek “phaneroein-” visible + Greek “thymos” soul, thus “visible soul”).[9] 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).

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.[10] 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.[11]

Almost all antidepressant drugs, especially atypical ones like mirtazapine and trazodone, are 5-HT2A antagonists, from moderate to very strong, and thus often totally disrupts psychedelic effects. Furthermore, persons on chronic antidepressive medications virtually can’t get any effects from serotonergic psychedelic drugs even after discontinuing antidepressant drugs.[citation needed]

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.[12] 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.[13]

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[14] and there being no evidence to support long term harm on mental health[15] 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.

The rest is here:

Psychedelic drug – Wikipedia

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.

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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 Katherine 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

View post:

Tim Ferriss: depression, psychedelics, and emotional …

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. In fact, two studies conducted using psilocybin in a psychotheraputic setting reveal that psychedelic drugs may assist with treating alcohol and nicotine addiction.[4]

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.

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.[5][6]

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.[7] 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.[8]

Aldous Huxley had suggested to Humphry Osmond in 1956 his own coinage phanerothyme (Greek “phaneroein-” visible + Greek “thymos” soul, thus “visible soul”).[9] 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).

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.[10] 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.[11]

Almost all antidepressant drugs, especially atypical ones like mirtazapine and trazodone, are 5-HT2A antagonists, from moderate to very strong, and thus often totally disrupts psychedelic effects. Furthermore, persons on chronic antidepressive medications virtually can’t get any effects from serotonergic psychedelic drugs even after discontinuing antidepressant drugs.[citation needed]

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.[12] 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.[13]

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[14] and there being no evidence to support long term harm on mental health[15] 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.

See the original post:

Psychedelic drug – Wikipedia

List of psychedelic drugs – Wikipedia

The following is a list of psychedelic drugs of various classes. Serotonergic psychedelics are usually considered to be the classical psychedelics, whereby the other classes are often only considered to have secondary psychedelic properties. Some of these compounds may be classified differently or under several categories, due to unique structural classification, multiple mechanisms of action, or to the fact that the precise pharmacodynamic actions of psychedelic drugs are not yet completely understood. Also, due to the vast amount of possible substitutions and analogs of psychedelic compounds, their total number is quite large and is not fully reflected within this list, leaving room for many that have not yet been sufficiently investigated and even others that have not yet been discovered.

Entries marked with a ‘#’ are naturally occurring compounds.

Read more:

List of psychedelic drugs – Wikipedia

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:

Problem-solving

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.

Creativity

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.

Mood

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.

Physical

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.

Read more from the original source:

Beginners Guide to Microdosing Psychedelics

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