Compass announces Phase 3 synthetic psilocybin results; DEA moves two psychoactive research chemicals to Schedule I; and New Zealand Ministry of Health approves prescription psilocybin
Plus: Iowa governor vetoes Compass trigger law bill, and Will travel for psychedelics
Happy Friday and welcome back to The Microdose, an independent journalism newsletter brought to you by the U.C. Berkeley Center for the Science of Psychedelics.
Compass announces Phase 3 synthetic psilocybin results
On Monday, psychedelics company Compass Pathways announced results from their Phase 3 trial using COMP360, their formulation of synthetic psilocybin, in treating treatment-resistant depression. The results have not yet been peer reviewed, but in a press release, Compass described the results as a “highly statistically significant reduction in symptom severity.”
In the trial, 258 participants — the largest psilocybin clinical trial to date — received either a single 25mg dose of COMP360 or a 1mg placebo dose. Alongside that dose, participants received what Compass calls “psychological support” — a form of education and support provided by a licensed mental health professional that focuses on safety and “minimal intervention,” unlike more involved psychotherapy approaches. Researchers compared participants’ baseline scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard depression questionnaire, to their scores six weeks after taking psilocybin. Scores of participants who received the 25mg dose were on average 3.6 points lower than those who had received the placebo dose.
Compared with the company’s Phase 2b results, published in The New England Journal of Medicine in 2022, these outcomes are certainly less splashy. In Compass’s Phase 2b study, the difference in MADRS scores between participants who received a 25mg dose of COMP360 and those who received the 1mg dose was, on average, 6.6 points, nearly twice that of what the company reported for this Phase 3 trial.
When Compass announced its earlier Phase 2b results before data were peer-reviewed and published, it included information about how many participants in each study arm showed a 50% or greater reduction in MADRS score. But the new Phase 3 results did not include this information. We reached out to Compass for more information, and the company’s vice president of communications Dana Sultan-Rothman said that the company does not yet have that data.
The decision not to make more data available could be at the direction of federal regulators; per reporting from the health and science news site STAT, “Compass released limited results because the FDA instructed the company to do so, for fear that releasing more data could influence participants’ experiences in the ongoing trial.”
When the company’s Phase 2b results were published in 2022, many researchers expressed concerns about participants’ high rate of adverse effects: 61% of participants who received a 25mg dose of COMP360 reported adverse effects and 38% of the 1mg (placebo) group reported adverse effects. In the company’s press release for their Phase 3 results, Compass did not include data about adverse effects but mentioned that an independent Data Safety Monitoring Board “reviewed safety data for COMP360 and found no unexpected safety findings and no clinically meaningful imbalance in suicidal ideation between treatment and placebo arms.”
Apparently, investors were not impressed: after the results were published Monday, Compass’s stock price fell by nearly 50%, from $4.63 to $2.35.
DEA moves two psychoactive research chemicals to Schedule I
Last Friday, a U.S. Drug Enforcement Administration judge published his ruling that DOI and DOC be placed in Schedule I of the Controlled Substances Act. The two drugs in question — 2,5-dimethoxy-4-iodoamphetamine (DOI) and 2,5-dimethoxy-4-chloroamphetamine (DOC) — are primarily used by psychedelics researchers to understand how psychedelics work in the brain. Researchers currently use DOI and DOC because many other psychedelics are already classified as the most restricted Schedule I drugs and as a result procuring those substances for research requires many additional steps.
The DEA first attempted to classify DOI and DOC as Schedule I drugs in April 2022, but the DEA withdrew its proposal after outcry from scientists and psychedelics advocates. The agency introduced another proposal in December 2023, which was again met with criticism from researchers and psychedelics advocates, who said scheduling the drug would hinder psychedelic research and business. The DEA held a 6-day hearing to consider its DOI/DOC proposal, during which researchers testified about the drugs’ role in research, and the DEA argued that the drugs have abuse potential, citing posts from social media sites including Reddit. Shortly after the hearing concluded, researcher Alaina Jaster told The Microdose that one day of the hearing was devoted to discussing such posts and whether they were real. “We had a very interesting conversation about what it means to be a Reddit troller or sh*tposter,” Jaster said at the time.
In U.S. Administrative Law Judge Paul Soeffing’s ruling, he noted that he discounted the testimony citing Reddit threads. “I find these anonymous posts on social media to be unreliable hearsay,” he wrote in a footnote. But he nonetheless concluded that the drugs have abuse potential because of their pharmacological similarities to other Schedule I drugs, and because there is “substantial” evidence that some people are taking the drugs.
“The ruling rests on illogical conclusions, ignoring evidence presented by many of the world’s top experts, instead giving almost complete deference to the testimony of a single DEA scientist,” said Robert Rush, the attorney for Dr. Raul Ramos, a petitioner in the case and neuroscientist at University of California, Berkeley, in a statement released by Students for Sensible Drug Policy. (SSDP was another petitioner in the case.) “The judge afforded excessive deference to the government's witnesses, accepting their assertions without adequate scrutiny, while unjustifiably discounting the testimony of world-class researchers and experts who are at the forefront of psychedelic science.”
SSDP says the petitioners’ legal teams are exploring the potential to appeal the decision.
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New Zealand Ministry of Health approves prescription psilocybin
Last week, New Zealand’s Ministry of Health granted a psychiatrist approval to prescribe psilocybin for treatment-resistant depression. In a press release, the agency said it was the first time the country has allowed for psilocybin to be used outside of research. So far, the agency has given approval to just one person: Cameron Lacey, a psychiatrist who conducted the first psilocybin-assisted therapy study in the country. But the agency says that single approval will pave the way for other practitioners to also request prescriber status, and that they are “currently developing guidance to assist with the application process.”
“New Zealand is now in line with Australia, where authorised prescribers have been using psilocybin in clinical settings for some time,” said David Seymour, New Zealand’s Minister of Regulation and Associate Minister of Health, Finance, Justice and Education in a press release.
Iowa governor vetoes Compass trigger law bill
Two weeks ago, Iowa Governor Kim Reynolds vetoed Iowa House File 383, a bill that would have allowed clinicians to prescribe “crystalline polymorphic psilocybin, also known as COMP360” — Compass Pathways’ formulation — if the drug were to be approved by the U.S. Food and Drug Administration. (In addition to Iowa, Compass lobbyists put similar bills in front of lawmakers in Colorado, Virginia, and Kansas.) The bill had passed the Iowa House and Senate unanimously before it was vetoed.
In her letter, Governor Reynolds wrote that the bill “moves ahead of where our public health systems, regulatory frameworks, and law enforcement infrastructure are prepared to go at this time,” and that psilocybin “should first be FDA approved and rescheduled by the DEA before the State of Iowa considers rescheduling.”
“This decision is not a dismissal of the emerging science or the sincere advocacy behind this legislation,” she concludes. “Rather, it is a call for a more deliberate and Iowa-centric approach— one that engages state and federal partners, provides time to review any clinical studies and federal changes, and builds a framework for any future therapeutic access that is clear, safe, equitable, and medically sound.”
Will travel for psychedelics
Last week, Rocky Mountain Poison and Drug Safety, a division of the nonprofit Denver Health and Hospital Authority, announced results from their National Survey Investigating Hallucinogenic Trends. Between April and June 2024, researchers surveyed more than 2,100 adults online across the U.S. about their drug use. In their announcement, RMPDS did not specify how many people had used psychedelics in the last year, but mentioned that about a third of those people said they had traveled to do so, and that 43% traveled to Colorado and 29% to Oregon, while another 39% travelled internationally. Full results from the survey will be published in the Annals of Emergency Medicine later this year.
For New York Magazine, journalist Kimon de Greef digs into the race between Beckley Psytech and GH Research, the two companies looking to develop 5-MeO-DMT, sometimes called the “God molecule.” “The contest between Beckley and GH mirrored a conflict playing out in the psychedelics gold rush at large — one between longtime adherents and opportunistic outsiders, between the psychedelic faithful, who understood the power of the drugs, and extractive business interests, whom many believed did not,” de Greef writes.
Last year, many Massachusetts psychedelics advocates organized around Question 4, a ballot measure that would have allowed people to use and cultivate psychedelics including psilocybin, ibogaine, mescaline, and DMT. Ultimately, the measure failed, and Jack Gorsline reports for Lucid News that two former campaign staffers are alleging that New Approach and Massachusetts for Mental Health Options — the groups that largely bankrolled the Measure 4 campaign — may have violated campaign finance laws.
A 2024 meta-analysis of how psychedelics affect brain-derived neurotrophic factor (BDNF), a molecule important for neuronal plasticity, has been retracted, reports The Transmitter. The paper was originally published in the Journal of Psychopharmacology, and the retraction notice says a reader reached out to the authors with concerns, and that the authors requested that they revise the article to correct data and analyses. The journal’s editors and its publisher, SAGE, said that the requested revisions “calls into question the reliability of the original research and the conclusions.”
NPR’s All Things Considered profiles the Colorado Psychedelic Church, a “spiritual community that uses psychedelics in communal ceremonies.” As one member told the show: “It is more about the community than the substances.”
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