Monthly Archives: February 2022

Once counterculture staples, LSD and magic mushrooms are starting to trip out another world: psychiatry. A smallbut rapidly growinggroup of doctors is embracing the drugs as powerful tools against a myriad of mental demons. People suffering from depression, substance abuse, and post-traumatic stress disorder (PTSD) have all benefited from psychedelics in small controlled trials. Psychedelics, over 50 years after the Summer of Love, have once again taken flight.

With one caveat: they get people high. While a perk for recreational users, the mind-altering effects can be a serious detriment to patients. For now, treatments are carefully administered and monitored inside clinics rather than patients taking pills at home. Regulatory hurdles further prohibit widespread adoption.

But what if theres a way to strip away the high and leave only the drugs therapeutic effects?

Enter crystals. This week, a team extracted and crystallized the structure of psychoactive drugs docking in the brain. Using X-rays, they mapped out the interactions at the nanoscale level, teasing apart those that can lead to hallucinations from those that can calm troubled minds. Knowledge in hand, they engineered several synthetic cousins of LSD, which helped quell depressive symptoms in mice without signs of the critters getting high.

While it could be a long road from mice to men, the study is one in a series of high-profile works that seek to strip the hallucinogenic magic from psychedelics, instead adding a sprinkle of healing magic. For now, they wont be silver bulletsthe mice needed a hefty dose to dampen their depression, which is a red flag for potential side effects.

But the implications are profound. If validated in humans, the drugs would lay the groundwork for an entirely new treatment regime for mental troubles that haunt millions of people.

This work is going to generate a lot of interest, Dr. Bryan Roth at the University of North Carolina School of Medicine, an expert in the field who was not involved in the study, said to Science.

Psychedelics were all the rave in the 50s and 60s, and not just in the party scene, but also in psychiatry. At the time, treating patients with LSD, psilocybin (the active component in magic mushrooms), or MDMA (also known as molly or ecstasy) was considered a promising alternative to other therapies for restoring health and autonomy for people confined long-term in asylums. Over the decade, scientists tested roughly 40,000 people in over 1,000 studies for treatment of mental health and addiction issues.

Despite initially promising (though rudimentary) results, the studies lurched to a halt when psychedelics were banned as a backlash to widespread recreational use.

Yet neuroscientists never stopped examining their potential, even at the risk of their careers. A breakthrough came in the 2010s, when several studies showed that ketamine, a horse tranquilizer and party drug, had jaw-dropping effects for depression. Unlike other antidepressants, which often take months to workif they work at allketamine triggered beneficial effects in some people with just one dose, and within hours.

Initially met with skepticism and considered too good to be true, rigorous studies further showed that in mice, ketamine boosted the birth of new neurons in the brain while tweaking neural networks to be more adaptable. In 2019, a form of ketamine was approved by the FDA as the first truly new antidepressant in decades, hailed as a game changer for depression and a turning point for the return of psychedelics as a potential therapeutic force. It also immediately raised the question: can we make a non-hallucinogenic alternative?

As ketamine began its rebound into psychiatric prominence, other drugsincluding LSD, psilocybin, and MDMAalso started their arduous journeys of reentering medical respectability. Between 2010 and 2020 clinical trials tripled, with several showing dramatic effects. One trial found that seven out of ten people who took psilocybin reduced their symptoms by half. Other clinical trials, mostly conducted in the UK and Canada, are entering late stage.

To overcome regulatory hurdles, however, structural biologists have taken a different route: altering the structure of these chemicals, in turn stripping away their ability to trigger an unwanted trip.

It starts with visualizing where the chemicals impact the brain. The crux is a receptor called 5-HT2AR. The receptor isnt evolved to get us high; rather, its a critical protein dock for serotonina brain chemical or neurotransmitterthats involved in many of our base functions. Mood is one of them, which is why most common antidepressants today target these receptors.

Like the Los Angeles port, 5-HT2AR has multiple docking sites for chemicals, each triggering a different supply chain route. Depending on the docking station, the same cargothe drugchanges how the neuron reacts by recruiting other molecular providers. Depending on those providers, the drug tweaks the neural circuit in diverse ways, altering the brains response to the drug.

In the new study the team hunted down the provider proteins that trigger antidepressant effects. They first doused multiple mouse brains with different drugs, including LSD, magic mushrooms, serotonin, and a non-hallucinogenic therapy for Parkinsons disease. They then crystallized the 5-HT2AR dock and examined how the chemicals interacted with it at the atomic scale with X-ray beams.

Surprisingly, many psychedelics turned out to be shape-shifters. Rather than docking at one spot, they were able to contort and bind to another nearby cavity. Turning to mice, they teased apart how the different docks worked. One dock, for example, led the mice to twitch their heads, a sign of getting high. Another, when tested for depression, alleviated the symptoms.

Guided by the 5-HT2ARs docking map, the team engineered multiple LSD cousins that preferably bind to the anti-depressant dock. Repeating the experiment, they found two chemicals (with the non-catchy names of IHCH-7079 and IHCH-7806) that had antidepressant activity, without the head-twitching normally seen with LSD or psilocybin.

The study is one of many following the recipe towards a new generation of mind-healing rather than mind-bending substances. How they work remain a mystery, which is why intricate scrutiny of 5-HT2AR and other serotonin receptors is the current playbook.

On the front line are Dr. David Olson at the University of California, Davis, and Dr. Bryan Roth at UNC-Chapel Hill. Several years back, Olson synthesized near a dozen chemicals similar to LSD, with a promising result called TBG (tabernanthalog) that also binds to serotonin receptors. In mice, the drug boosted the neuronal infrastructure for learning, and cut down substance-seeking behavior in rodents. Mid-2021, a single dose of the drug was further found to be effective for stress disorders in mice. Delix Therapeutics, a company co-founded by Olson, is rapidly exploring the new drugs for clinical use, with trials potentially starting later this year.

Meanwhile, Roth has worked to decipher the structure of 5-HT2AR when bound to psychedelic compounds. The seminal study, in 2020, gained a first glimpse into how they act. Given the remarkable efficacy of psilocybin for depression (in Phase II trials), we are confident our findings will accelerate the discovery of fast-acting antidepressants and potentially new drugs to treat other conditions, such as severe anxiety and substance use disorder, he said at the time.

For now, the authors preach caution. Similar to previous non-hallucinogenic cousins, their molecules need a high dose to see anti-depressant effects. But the new structural maps add to a growing atlas to help guide non-hallucinogenic drugs forward. This additional structural data will aid efforts to design new antidepressants as well as antipsychotics, said Olson.

Image Credit: GDJ / 10433 images

Looking for ways to stay ahead of the pace of change? Rethink whats possible. Join a highly curated, exclusive cohort of 80 executives for Singularitys flagship Executive Program (EP), a five-day, fully immersive leadership transformation program that disrupts existing ways of thinking. Discover a new mindset, toolset and network of fellow futurists committed to finding solutions to the fast pace of change in the world. Click here to learn more and apply today!

View post:

Psychedelics Without the Trip Could Be 'Healing Magic' for Mental Health - Singularity Hub

Senate Majority Leader Chuck Schumer (D-NY) announced at a press conference on Friday that he is aiming to formally file his much-anticipated bill to federally legalize marijuana in April. House Judiciary Committee Chairman Jerrold Nadler (D-NY), who also spoke, discussed progress on his separate legalization bill.

Both top lawmakers detailed their efforts to end prohibition at an event in New York City, which also involved House Small Business Committee Chairwoman Nydia Velazquez (D-NY), New York lawmakers and advocates with the Drug Policy Alliance and other organizations.

Friday proved to be an especially eventful day for federal cannabis policy, as the House earlier passed a large-scale bill that contains the bipartisan Secure and Fair Enforcement (SAFE) Banking Act. Its the sixth time that reform has cleared the chamber in some form.

In the coming weeks, were ramping up our outreachand we expect to introduce final legislation. Our goal is to do it in April, Schumer said at the New York event. Then we begin the nationwide push, spearheaded by New York, to get the federal law done. As majority leader, I can set priorities. This is a priority for me.

Advocates were encouraged when Schumer first disclosed details about his Cannabis Administration & Opportunity Act (CAOA), which he unveiled in draft form for public comment in July, but theyve grown impatient with his repeated comments in the months since that a formal introduction was coming soon. Now hes set a target timeline, and the leader also separately said in a meeting with activists that he expects committee hearings on the proposal shortly after its finally filed.

Right now, were taking those comments [on the draft version] and reaching out to Democratic and Republican senators, Schumer said, adding that we have some Republican support. Its not clear if hes indicating that there will be GOP cosponsors on the bill itself or if hes referencing general support from voters and some lawmakers across party lines for ending prohibition.

If any senators have other ideas that they want to add to the bill, as long as it keeps social and economic justice as the spearhead, were happy and willing to listen, he said.

Even if committee hearings start quickly following an April introduction, it seems highly unlikely that it will pass and make it to the presidents desk by the unofficial cannabis holiday 4/20, as Schumer said he wanted to see happen in a Senate floor speech delivered last April 20.

Schumer, Nadler, several New York lawmakers also made the case at Fridays event that while New Yorks legalization law, which is actively being implemented, should serve as a model for the country, comprehensive equity will only be achievable once federal prohibition is lifted.

We want to renew the case for comprehensive marijuana reform that repairs the harm of the war on drugs at the federal level, using the great work that has been done here in New York as an example and way to lead, Schumer said, adding that just because we have a state law, the federal law still creates problems, and thats why one of the many reasons we need to change it.

The majority leaders office has been involved in negotiations with advocates and stakeholders, both on his legalization measure as well as the SAFE Banking Act, which he was blamed for blocking as part of a separate defense bill late last year.

The leader and colleagues have insisted on passing comprehensive legalization first before bankingbut the sponsor of the banking bill, Rep. Ed Perlmutter (D-CO), told Marijuana Moment on Friday that, after initiating conversations with the leaders office, there may be a path forward to advance his legislation through both chambers with equity-focused amendments that Schumer wants to see.

With respect to Schumers legalization bill, the Senate leader emphasized late last year that he wants to keep the big boys out of the marijuana industryin favor of creating opportunities for smaller operators when cannabis is federally legalized, and he said that his upcoming bill would accomplish that.

We dont want the big boys to come in, he said at the time. After all the pain thats been occurring in communities like the one you represent in Brooklyn, where Im fromto have the big boys come in and make all the money makes no sense.

Hes made similar remarks in the past, stressing that his reform bill will take specific steps torestrict the ability of large alcohol and tobacco companiesto overtake the industry.

Nadler, meanwhile, discussed on Friday his Marijuana Opportunity, Reinvestment and Expungement (MORE) Act, which would also end federal prohibition and promote social equity in the industry like CAOA. That bill passed the House in a historic first last session, and it cleared Nadlers Judiciary Committee again in September.

The war on drugsand particularly the criminalization of marijuanahas been a failure that has unleashed untold suffering on millions of Americans, especially within minority communities, Nadler said. I am proud to stand here with Senator Schumer, and with the many other legislators and advocates with us today, who are leading the way in reforming our laws and bringing justice to those who have been harmed by these unfair and destructive policies.

Also at the event, Velazquez talked about the importance of ending prohibition, as well as opening up Small Business Administration (SBA) resources for marijuana businesses.

Change will not happen, change will not come, unless we demand it, the congresswoman said. And because we have been demanding it, public opinion has changed dramatically. So it is time for government to act, particularly the federal government.

Dan Goldman contributed reporting from New York.

Marijuana Banking Sponsor Says Hes In Amendment Talks With Senate Leader As House Passes Reform For Sixth Time

Photo courtesy of Mike Latimer.

More here:

Utah Lawmakers Vote To Study Benefits Of Psychedelics In Treating Mental Health Disorders - Marijuana Moment

Welcome to TDRs review of the Top 5 Psychedelic developments for the week of January 31. Aside from presenting a synopsis of events, we provide market commentary to summarize the week that was for publicly-listed companies.

5. Health Canada Denies Healthcare Practitioners Section 56 ExemptionsAfter Granting Them To A Group In 2020

In a move that has stunned patient advocates and healthcare practitioners who have spent months awaiting a response from the federal health agency, Health Canada has denied dozens of requests for Section 56 exemptions to access and use psilocybin for training purposes.

Thread

BREAKING: Health Canada has just notified TheraPsil anddozens of health care professionals seeking psilocybin access and training that their section 56 exemptions are to be denied. (1/ )

Non-profit organizationTherapsilbroke the news on Twitter on Wednesday morning, pointing out that the denied applications will have a much greater impact than on those whose applications were denied, potentially affecting over 1,000 additional healthcare professionals on its training waiting list who had hoped to apply for exemptions.

The decision is particularly confusing because Health Canadahas already provided exemptionsto people who had applied with the same intent.

4. Washington Legislature Hears Proposal to Legalize Psychedelic Mushrooms

Anyone 21 and older in the state of Washington could gain access to psychedelic mushrooms in 2024 if a proposal being heard in the Legislature passes this session.

I do not believe it belongs because its not addictive and generally not dangerous when theres a set and setting.

A Senate bill would direct the Department of Health to create a system allowing for anyone 21 or older to take mushrooms at a state-licensed center under the direct supervision of licensed facilitators. Individuals medically unable to travel to a center may be able to take mushrooms at home.

Prime sponsor Jesse Salomon, D-Shoreline, said he became interested in mushrooms after the Legislature dealt withthe effects of the Blake v. State drug possession ruling. Psilocybin is grouped with heroin and meth as some of the most dangerous drugs under the federal Controlled Substances Act. But Salomon said mushrooms and their history as a medicinal product are different from heroin and meth.

__________

Ongoing Phase 2, Phase 3, And Pre-Registration Programs In Psychedelics

__________

3. Psychedelic Stocks Outperform As Biopharma Stocks Stabilize

The psychedelic sector gained modestly this past week, although volumes were mostly lower across the board. TheHorizon Psychedelic Stock Index ETF(PSYK) rose4.18%, registering just its 3rd gain over the past 12 weeks. The rise is PSYK solidly outperformed its biopharma peers such as the Nasdaq Junior Biotechnology Index(2.68%) andNasdaq Biotechnology Ishares ETF(2.07%). The broad markets remained volatile, but did finish moderately higher despite Thursdays purge in equity markets. TheNASDAQadvanced 1.76% while the S&P 500climbed 1.52%. Heres how the Health Care (biotechnology) sector performed this week.

Not a whole lot of groundbreaking news on the psychedelic research front. From a capital markets perspective, it was nice to see the sector stabilize in the face of whipsawing volatility. We count 8 companies that registered triple-digit weekly gainsup from 4 last week. This was mostly due to sellers retreating after a long and drawn-out period of bear market action. Were looking for bottom-base building to delineate the markets floor before to inspire confidence that the bear impulse has ended. An important tell will be when PSYK ETF breaks its weekly 7EMA on strong volume.

EHVVF +23.75%, LOBE +20%, PWR +15.38%, DMT +13.95%, PULL +11.76%, WUHN +11.07%, OPTI +10.8%, BRAXF +10.68%, MMED +9.2%, BRAX +8.33%, MNMD +7.69%, FTRP +6.4%, MSET +5.19%, BETR +4.76%, ENBI +4.17%, ATAI +3.85%, SPOR +3.08%.

In the news

Awakn Life Sciences became the latest psychedelic company to obtain coverage under theH.C. Wainwrightumbrella. The New York investment bank initiated Awakn with a Buy rating and $10 price target.

Braxia Scientific provided an update on the companys leading research role within the psychedelics industry. Braxias team of researchers also continue to carry out multiple psychedelic-based clinical research trials, adding to its large and growing proprietary dataset critical to informing future drug development.

Colorado activists file competing psychedelics legalization ballot initiative for 2022.

Cybin Inc. reiterated by Oppenheimer with an Outperform rating and US$10 price target.

Elemental Advisorshas announceda new psychedelics ETF will soon be available topsychedelics investors. The ETF will trade under the symbol ofPSYKon theNew York Stock Exchange.

Entheon Biomedical announced the approval by the local Dutch ethics committee of EBRX-101, a comprehensive phase I clinical trial evaluating the pharmacokinetics, pharmacodynamics and safety profile of N,N-dimethyltryptamine (DMT).

Field Trip Health plans to release financial results for the fiscal third quarter ended December 31, 2021, after market close on Tuesday, February 15, 2022.

A Maine state lawmaker and others who testified at a legislative hearing on Tuesday have said they would like to see psilocybin allowed for people 21 years and older in order to treat people for depression or PTSD.

Mind Cure Health announced the hiring of Dr.Clare Purvis, formerly Headspace Inc.s Vice President of Clinical Product and Content Development, for the companys newly created role of Chief Product Officer to focus on building and expanding the reach of iSTRYM, its digital therapeutics platform

Mindset Pharma has synthesized additional promising candidates from its Family 3 of next generation drug candidates, and will initiate Proof of Concept preclinical studies to further measure the viability of these compounds as daily pro-cognitive take-home medication.

Mydecine Innovations has appointed Dr. Victoria Hale to the companys Board of Directors. Dr. Hale is a pharmaceutical scientist and executive, as well as a global health social entrepreneur. She currently serves as Chair of the Board of the Multidisciplinary Association for Psychedelic Studies (MAPS).

Mydecine also announced preparation for its FDA pre-Investigational New Drug meeting on February 28th, the company has submitted a pre-IND briefing package to the U.S. Food and Drug Administration for a clinical study evaluating MYCO-001 in a structured smoking cessation treatment program.

A Seattle doctor specializing in end-of-life care filed a formal petition with the U.S. Drug Enforcement Administration this week challenging the governments Schedule I classification of psilocybin, the main psychoactive component of psychedelic mushrooms.

Small Pharma published its third quarter results for the three and nine months ended November 30, 2021.

Tryp Therapeutics announced a non-brokered private placement to its co-Founder and Executive Director, William J. Garner, M.D. The Placement consists of 11,111,111 million units at a price of $0.18 per unit, with one common share warrant for each unit, to raise gross proceeds of approximately $2.0 million.

2. Report Shows Oregon Drug Decriminalization Has Dramatically Reduced Arrests And Increased Harm Reduction Access One Year After Enactment

According to information shared withFilterby the Drug Policy Alliance, there were 60 percent fewer total drug arrests in state over the 10 months after February 1, 2021, compared with the same period the previous year. That 2020 period saw 9,100 drug arrests in totalmeaning a reduction of almost 5,500 arrests. However, the data do not yet show the extent to which this decline was attributable to Measure 110.

Measure 110 also requires that a portion of cannabis tax revenue be put into a special fund to expand services for people who use drugs. Before the measure passed, Oregonrankednear the bottom of all U.S. states for access to substance use disorder (SUD) treatment.

Thanks to the measure, the state has already paid out over $31.4 million to providers of services including treatment, harm reduction, peer support, and housing and employment support. Gov. Kate Brown (D) had initially wanted to delay payments until July 2022, but advocates toldFilterthat they successfully fought to get this money paid out early, helping to keep critical services running.

1. Utah Lawmakers Vote To Study Benefits Of Psychedelics In Treating Mental Health Disorders

A Utah House committee approved a bill on Thursday that would create a task force to study and make recommendations on the therapeutic potential of psychedelic drugs and possible regulations for their lawful use.

Utah Lawmakers Vote To Study Benefits Of Psychedelics In Treating Mental Health Disorders: "If this is a tool that can help, we need it in our toolboxbut it needs to be safe, and we need to do it the right way." https://t.co/2vxKGgoct6

The legislation, sponsored by Rep. Brady Brammer (R), passed the House Health and Human Services Committee in a 10-1 vote.

The bill would create a Mental Illness Psychotherapy Drug Task Force that would be required to study and make recommendations on drugs that may assist in treating mental illness. The psychotherapy drugs that the panel would consider are defined as controlled substances that are not currently available for legal use and may be able to treat, manage, or alleviate symptoms from mental illness.

Read more:

TDR's Top 5 Psychedelic Developments For The Week Of January 31 - The Dales Report

A commonly held belief that classic psychedelic therapy can trigger suicidal thoughts, actions, or other types of self-harm is not supported by research, and, in fact, the opposite may be true.

Results from a meta-analysis of individual patient data showed that psychedelic therapy was associated with large, acute, and sustained decreases in suicidality across a range of clinical patient populations.

"This is the first analysis to synthesize suicidality outcome data from recent clinical trials with psychedelics. It gives us a better understanding of the effects of psychedelics on suicidality in the context of clinical trials," study investigator Cory Weissman, MD, Department of Psychiatry, University of Toronto, Canada, told Medscape Medical News.

The evidence suggests psychedelic therapy "may reduce suicidal ideation when administered in the appropriate setting and offered to carefully screened patients," Weissman said.

The findings were published online January 18 in The Journal of Clinical Psychiatry.

The analysis included seven psychedelic therapy clinical trials that had data on suicidality. Five of the trials used psilocybin plus psychotherapy, and two used ayahuasca plus psychotherapy. All seven trials had a "low" risk of bias.

Patients included in the trials had treatment-resistant major depressive disorder (MDD), recurrent MDD, AIDS-related demoralization, and distress related to life-threatening cancer.

The meta-analytic results showed significant decreases in suicidality at all acute time points (80 to 240 minutes post administration) and at most post-acute time points (1 day to 4 months post administration).

Effect sizes for reductions in suicidality were "large" at all acute time points, with standardized mean differences (SMD) ranging from -1.48 to -1.72, and remained large from 1 day to 34 months after therapy (SMD range, -1.50 to -2.36).

At 6 months, the effect size for reductions in suicidality with psychedelic therapy was "medium" (SMD, -0.65).

Large effect sizes for reductions in suicidality occurred across the different patient populations represented in the trial, the investigators note.

No study reported any suicide-related adverse events because of administration of a psychedelic. There were also "very few" acute (6.5%) or post-acute (3.0%) elevations in suicidality, "providing support for the safety of psychedelic therapy within controlled contexts," the researchers write.

They caution, however, that large controlled trials that specifically evaluate the effect of psychedelic therapy on suicidality are needed.

In an accompanying editorial, Daniel Grossman, BS, and Peter Hendricks, PhD, Department of Health Behavior, University of Alabama at Birmingham, note that results of this review warrant "optimism" for use of psychedelics for treatment of suicidality.

Based on this study and others, classic psychedelic therapy for suicidality appears to be a "promising avenue" for further investigation, they write.

However, research and anecdotes about increased suicidality and other self-harm attributed to psychedelic therapy, "though evidently rare, remain a critical concern" for further research to address, Grossman and Hendricks add.

The hope is that future research "clarifies who is most subject to these risks, what factors best identify them, and how best to navigate their treatment safely," they write.

The meta-analysis had no funding. Weissman receives funding from the Brain and Behavior Research Foundation and serves on the advisory board of GoodCap Pharmaceuticals. Hendricks is on the scientific advisory board of Bright Minds Biosciences Ltd, Eleusis Benefit Corporation, and Rest Pharmaceuticals Inc.

J Clin Psychiatry. Published online January 18, 2022. Abstract, Editorial

For more Medscape Psychiatry news, join us on Facebook and Twitter.

The rest is here:

Psychedelic Therapy and Suicide: A Myth Busted? - Medscape