New clinical trial results suggest a single psilocybin dose can significantly reduce depression symptoms for weeks; Comments on FDA’s draft psychedelics guidance; MDMA therapy for teens?

Plus: State updates in CA and MA, and a call for a psychedelics advisory group in the EU

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.

New clinical trial results suggest a single psilocybin dose can significantly reduce depression symptoms for weeks

Last week, JAMA published results from psychedelics research non-profit Usona Institute’s phase 2 trial suggesting that a single dose of psilocybin could treat major depressive disorder. Researchers assessed 104 participants’ depression levels using a common depression scale called the Montgomery-Asberg Depression Rating Scale (MADRS) and a week later gave them either a single 25 mg dose of psilocybin or an active placebo (niacin). After their psilocybin session, participants had a four-hour integration session, and they completed the MADRS scale five more times over the following six weeks to capture changes in their depression symptoms. Compared to participants who received niacin in their dosing session, participants who received psilocybin showed significantly reduced depression symptoms six weeks after treatment. 

Other clinical trials, like those from psychedelics company COMPASS and researchers at the University of Zurich, have also investigated the efficacy of a single dose of psilocybin in treating depression symptoms, but this new study shows some of the largest effects yet. Six weeks after treatment, participants who received the dose of psilocybin scored nearly 20 points lower on the MADRS compared with their baseline scores. (According to Canada’s Drug and Health Technology Agency, a MADRS score improvement of just two points is considered “clinically relevant,” with scores ranging from 0-60.) In the COMPASS trial, participants who received a 25 mg dose of psilocybin scored, on average, 12 points lower on the MADRS three weeks after treatment and in the Zurich study, participants’ MADRS scores were 13 points lower two weeks after treatment. (It should be noted that participants in the COMPASS study had a subtype of major depressive disorder known as treatment-resistant depression, whereas those in the Zurich and new Usona study had major depressive disorder.)

Via Raison et al (2023)

Public comment on FDA’s draft guidance

In late June, the U.S. Food and Drug Administration published its first-ever draft guidance on psychedelics clinical trials. Per usual governmental policy, the agency accepted public comments and suggestions on the draft for 60 days after publication. The agency received more than 200 comments from individuals and well-known psychedelics organizations. 

There were several major themes in commenters’ notes. Nurses and chaplains requested consideration as possible study monitors. In their comment, MAPS Public Benefit Corporation wrote that the draft guidance’s requirement that assistant monitors have bachelor’s degrees and a year of clinical experience could “unnecessarily limit the pool of providers needed to execute the research.” 

Many commenters took issue with the FDA’s assertion that psychotherapy’s contribution to psychedelics’ efficacy “has not been characterized.” For example, in their response letter, the American Psychedelic Practitioners Association wrote: “Given that therapy is a foundational element of the therapeutic potential of these drugs, FDA should acknowledge therapy as an integral component of current best practices for almost all indications with rare exceptions.”

In what is perhaps the most comprehensive response to the agency’s draft guidance, a letter submitted by non-profit organizations BrainFutures, Reason for Hope, the Veteran Mental Health Leadership Coalition, and two dozen other researchers and clinicians calls for the FDA to reconsider some of the core premises of its draft guidance, including its assertion that psychedelics have high abuse potential, and that study sponsors should design trials to eliminate potential confounding biases, like requiring that the in-session monitors not be the same individuals as those doing post-session therapy. The latter guidance, in particular, “could result in less effective care and worse patient outcomes for vulnerable patient populations, who benefit from the consistent therapeutic alliance,” the commenters write. Rather than prescribing requirements to reduce bias, the letter writers state that the FDA should “encourage sponsors to conduct clinical trials that control for and assess how various models of in-session and integration therapy and/or psychosocial support contribute to clinical outcomes.” 

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MDMA therapy for teens?

While MDMA treatment is being explored as a treatment for PTSD in adults, much less is known about whether such treatment might be safe and effective for teenagers. MAPS is expected to seek U.S. Food and Drug Administration approval for MDMA as a treatment for PTSD as early as next year, and it has plans to eventually conduct studies to establish its effects in children. In a new qualitative study published in Drug Science, Policy and Law, researchers in the Netherlands interviewed nine participants between the ages of 16 and 25, as well as their parents and clinicians, about their perceptions and associations of the drug, and about the risks and benefits of MDMA-assisted therapy.

Participants and parents initially expressed skepticism and concern about MDMA — one parent brought up its image as “a dangerous party drug,” while some of the young participants were concerned that it could harm their still-developing brains. Skeptical participants became more open to taking MDMA after viewing a video explaining the treatment. Meanwhile, clinicians were concerned about MDMA’s status as an illegal drug and the possibility that their clients might become addicted to the drug or experience even more intense depression after “the euphoric feelings experienced that day disappeared.” Clinicians also discussed the age at which participants should be free to participate in MDMA-assisted therapy; most felt 16 was too young but that 18-20 “might be more appropriate.” “Based on these findings, we conclude that if adequate information is provided, proper caution is employed, and the mentioned facets considered, stakeholders may be generally supportive of testing the feasibility of MDMA-AP for adolescents suffering from PTSD,” the authors write.

The State of Psychedelics: CA SB 58 survives suspense file, MA grassroots organization meets with state lawmakers

Last Friday, the California Assembly’s Appropriations Committee voted to pass Senate Bill 58, which would make it state-legal for people over 21 to possess, prepare, obtain, and transport mescaline (excepting peyote), DMT, ibogaine, psilocin, and psilocybin. In August, the committee placed the bill “on suspense file,” which requires the committee to review the bill’s fiscal impact. The bill will now continue to the full Assembly floor for a vote. Meanwhile, CBS News reports that parents whose children have died in accidents after taking psychedelics are calling on legislators to create public education and first responder training before proceeding with decriminalizing these substances. 

This week in Massachusetts, founder of grassroots psychedelics organization Bay Staters for Natural Medicine James Davis co-led a private briefing for state lawmakers and their staff. Davis and Sarko Gergerian, a lieutenant in the Winthrop, Massachusetts police department, encouraged attendees to support two psychedelics bills introduced to the state House and Senate in early 2023. The bills would decriminalize the possession, ingestion, obtaining, giving away, and transportation of less than two grams of psilocybin, psilocin, DMT, ibogaine, and mescaline; one version of the bill allows for people to grow psychedelics at home, while the other does not.

Advocacy group calls on European Union to create psychedelics advisory body

This week, the non-profit group Psychedelic Access and Research European Alliance (PAREA) submitted a brief to the European Medicines Agency (EMA), the EU agency that oversees the evaluation and supervision of pharmaceutical products, recommending that the agency create a central advisory group on psychedelics. The brief says the advisory body should include EMA officials as well as healthcare professionals, patient organizations, drug developers, and others to guide policy and issue periodic reports with recommendations for the field. “Centralized coordination would offer an efficient mechanism to propel the field forward, rather than individual EU countries initiating their own work groups,” the brief says. PAREA also recommends the EMA create a “cross-disciplinary professional entity” to supervise practices for training and accrediting medical professionals to administer psychedelics for clinical use. 

• In an op-ed for STAT, writer Danielle Meinert describes how she self-administered psilocybin to treat her avoidant/restrictive eating disorder, known as ARFID, which she was diagnosed with in childhood. “I cannot ethically recommend others try this for their ARFID. We just don’t have enough research,” she writes. “But for me, the risks psychedelics could pose felt much less concerning than the malnutrition and distress I was already living with.”

• The Denver Post explains why some people are using psilocybin before it’s legal. 

• In The San Francisco Chronicle, a retired police lieutenant argues in favor of the state’s efforts to make psychedelics more accessible. 

• Recordings from MAPS’s Psychedelic Science conference, held in Denver in June 2023, are now available online. (Read The Microdose’s coverage of the conference here.)

• Oregon’s Measure 109 was supposed to be funded entirely by licensing fees, but those fees aren’t yet covering the state’s costs. According to the Willamette Week, the Oregon Health Authority “is betting that shroom fee revenue will pick up as the biennium proceeds, making up the rest of the shortfall.” Until then, the state’s general fund will need to provide $3.1 million to Oregon Psilocybin Services over the next two years.

You’re all caught up! Have a great weekend. We’ll be back in your inbox on Monday with a new issue of 5 Questions. 

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