FDA makes public its letter to Lykos on MDMA bid; U.S. military adds psilocin to active duty drug testing; Mississippi looks to join the ibogaine train
Plus: Is psilocybin-assisted therapy cost-effective? And Psilocybin for longevity? Or did those tripping mice just eat less?
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.
FDA makes public its letter to Lykos on MDMA bid
On Thursday, U.S. Health and Human Services announced the release of 89 previously unpublished complete response letters (CRLs). The U.S. Food and Drug Administration sends CRLs to pharmaceutical companies notifying them that an application for a new drug has not been accepted. The letters lay out next steps the companies must take to advance the process. These letters have historically not been publicly available because they often contain proprietary information, but in recent years, scholars have questioned this practice and its implications for public transparency. For instance, a 2015 paper published in BMJ points out that press releases often obscure details from CRLs.
The batch of CRLs published Thursday includes the FDA’s response to Lykos Therapeutics’ application to use MDMA, or midomafetamine, as a treatment for PTSD, which the agency issued in August 2024. (Read our coverage of the FDA’s decision here; at the time, The Microdose submitted a Freedom of Information Act to the FDA for the Lykos letter, which was rejected.) The 10-page letter outlines the FDA’s concerns with Lykos’s data, all of which also came up during a special meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee held last June. Here were the FDA’s major points from their response letter,
Despite the FDA’s recommendations in previous communications that Lykos collect data on “positive” or “favorable” adverse events like euphoria or mood changes, the company did not do this in their Phase 3 clinical trials. “As you were specifically advised, regardless of whether a participant, therapist, or physician may find a drug experience to be neutral, positive, or favorable, events that are relevant to the abuse potential of a drug or potential for impairment should have been captured and reported in the safety and abuse potential summary in the NDA,” the letter states.
According to the FDA, the data do not capture how long the effects of MDMA last in treating PTSD. Both Phase 3 studies — MAPP1 and MAPP2 — only followed participants 8 weeks after their last dose of MDMA. A subsequent study — MPLONG — attempted to follow participants for longer, but the FDA took issue with the study’s design. According to their response letter, MPLONG included only one visit, and “there was marked variability in the timing of those visits, with a wide range of 6 months to up to 2 years of follow-up.” Additionally, they raised concerns that participants opted in to MPLONG, which creates “a potential for bias due to self-selection.”
Around 40% of the participants in the Phase 3 studies had previously tried MDMA, and the study had a high dropout rate between study enrollment and formal screening. (A briefing document released by the FDA last summer said the dropout rate for MPLONG was 25%.) “These two factors suggest the possibility of selection bias,” the letter states. “Not only does this potentially limit generalizability, it also raises the possibility of expectation bias given that participants who have prior experience with midomafetamine are more likely to recognize the effects of midomafetamine (i.e., leading to functional unblinding) and anticipate a treatment benefit.”
The FDA’s letter recommends Lykos conduct a new clinical trial and recommends specific design features of that trial. It also recommends that Lykos “consider an independent third-party data audit of all study records and reports, including the recordings of the treatment sessions, to identify unreported and under-reported adverse events.” A response from Lykos was required a year after receipt of the letter, which was sent to the company on August 8, 2024. We reached out to Lykos for comment on what steps, if any, it has taken in response to the requests outlined in the FDA’s letter but did not receive a reply by press time.
Meanwhile, as first reported by Psychedelic Alpha, Lykos Therapeutics plans to change its name to Resilient Pharmaceuticals. The name change was confirmed by Rick Doblin, who served as a Lykos board member. In a phone interview with The Microdose on Wednesday, Doblin said he likes the name “Resilient” but did not have a hand in choosing it. Lykos was spun out from Doblin’s non-profit organization MAPS as “MAPS Public Benefit Corporation” and was known as MAPS PBC. The name Lykos Therapeutics came later and is an ancient Greek word meaning wolf. “Over time, I felt the management was not really making decisions based on what’s best for public benefit, and I felt it was a wolf in sheep’s clothing,” says Doblin. “So when they changed their name to Lykos, it was at least a wolf in wolf’s clothing. Now that they’ve changed their name to Resilient, I hope that public benefit plays a bigger role.” The Microdose also reached out to Lykos for confirmation and comment about this but, again, did not receive a response before press time.
The new name is only the most recent change at the company following a major shakeup in ownership earlier this year. In May, the foundations of billionaire investor Antonio Gracias and hedge fund billionaire Christopher Hohn, gained a controlling stake in Lykos Therapeutics through a $50 million investment. Gracias is a long-time business associate and close friend of Elon Musk; he worked at the Department of Government Efficiency with Musk. An article in The Guardian last week goes behind the scenes of Gracias’s psychedelics advocacy, which includes time spent at Burning Man with Rick Doblin. The story delves into what that history might mean for Lykos, now Resilient Therapeutics, and the company’s future efforts to obtain regulatory approval for MDMA.
U.S. military to start drug testing active duty personnel for psilocin
According to both Military.com and Task & Purpose, the U.S. Office of the Under Secretary of Defense for Personnel and Readiness recently published a memo saying that U.S. service members may be drug tested for psilocin, the active metabolite of psilocybin, beginning October 1. The memo, per Task and Purpose, says the change is “due to the risk of impairment and subsequent deterioration of security, military fitness, readiness, good order and discipline.” The U.S. military already drug tests active duty members for many other substances including LSD and MDMA. If military personnel are found to have these substances in their systems they can face sanctions or even termination.
Meanwhile, Veterans Affairs researchers are studying the use of MDMA and psilocybin to treat PTSD, depression, and alcohol use disorder in military veterans.
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Mississippi looks to join the ibogaine train
The national profile of ibogaine, a psychoactive substance found in plants, continues to rise following legislation passed by Texas lawmakers in June that committed $50 million to ibogaine research. Last Thursday, Mississippi became the latest state to consider embracing ibogaine when the House and Senate public health committees held a joint hearing on the substance, organized by Representative Sam Creekmore (R), chairman of the House Public Health and Human Services Committee. Nearly four months ago, Creekmore appeared on a Mississippi talk show saying he’d been following the news in Texas and that he intended to introduce a similar bill in Mississippi.
Among those who provided public comments at the hearing were prominent voices connected to veterans groups advocating for the benefits of ibogaine including Trevor Millar, co-founder of Ambio, which owns and operates a Tijuana-based ibogaine retreat center ; Army veterans Myles Grantham and Ben Bush; and Claire Durst, nurse and former medical director of psychedelic veteran organization The Mission Within. Other speakers included the Mississippi Department of Mental Health’s medical director Tom Recore; Americans for Ibogaine ambassadors and twin sisters TK and Cipriana Quann; Geoffrey Lawrence, research director at the libertarian thinktank the Reason Foundation; and Americans for Ibogaine’s CEO W. Bryan Hubbard.
Over the course of the three-hour meeting, speakers touched on many of the same points brought up last week during a similar hearing held by Kentucky’s Interim Joint Committee on Health Services. Speakers pointed to recent ibogaine funding bills in Texas and Arizona, shared anecdotes of healing from people who had traveled to Mexico for ibogaine sessions, and presented an overview of the current state of ibogaine research.
Several lawmakers asked over the course of the hearing why there had not yet been clinical trials done with the drug. Lawrence told them that he supposed it was because ibogaine comes from a natural plant and is therefore not patentable. He also asserted that the states funding ibogaine research would have what he called “capital partners” and “have ownership interest in the final intellectual property that comes out of an FDA approval.” It’s unclear how such an arrangement would work. There are already companies including Gilgamesh and Delix working to develop synthetic, and therefore patentable, ibogaine. Those companies do not, as of yet, anyway, have any official involvement with these state efforts.
Is psilocybin-assisted therapy cost-effective?
While there is preliminary evidence that psilocybin-assisted therapy (PAT) can help treat depression, whether it’s cost-effective — especially compared to existing depression treatments — could ultimately determine its uptake. “Questions remain about its economic value,” write the authors of a new analysis of PAT’s cost-effectiveness published in Translational Psychiatry last Friday. “For instance, PAT requires more initial resources than conventional treatments; trials of PAT included 4–7 days of preparation, active dosing, and integration sessions with trained counselors and therapists.”
The paper modeled the cost-effectiveness of PAT as what’s known as a third-line treatment — meaning, the researchers assumed patients would have previously received two other treatments which did not achieve remission from depression symptoms. They then compared outcomes for psilocybin-assisted therapy against the general standard of care, which includes treatments like psychotherapy, antidepressant drugs, Spravato, and electroconvulsive therapy. The researchers’ model estimated parameters such as the probability of PAT resulting in remission from depression symptoms and relapse and the cost of a course of treatment, and they concluded that while PAT had a slightly better probability of positive health effects over the course of a year, it also likely cost more than $3600 more than standard treatments over that same period. If providers can keep costs below $5000, the authors say, then PAT “may offer economic value compared to available treatment-resistant depression treatments.”
Psilocybin for longevity? Or did those tripping mice just eat less?
Claims that psilocybin could slow aging are overblown, writes University of Southern Denmark neurobiologist Mikael Palner on a Danish science news site Videnskab.dk. The piece was translated into English for an essay published in The Conversation. Palner reviews the details of a recent study with rodents, in which mice treated with psilocin lived, on average, longer than those who did not get the substance. He points out — as we did in our write-up in July — that it’s unclear how the doses mice received would translate to human doses, which is true for any study in which rodents are administered drugs. Palner also points out that psilocin activates serotonin 2C receptors, which control appetite and metabolism. “We already know that eating less can reliably extend lifespan. So, at the very least, the study should have told us how much the mice were eating and how their weight changed throughout the study – just to make sure their longer lives weren’t simply because they were eating less,” Palner writes.
Public health research group Rocky Mountain Poison and Drug Safety released the latest results from their National Survey Investigating Hallucinogenic Trends report, which found that 5.5 million Americans used psilocybin in the last year, making it the most-used psychedelic in the country. Most users took drugs with friends or family in small, private settings.
Bloomberg covers Seattle physician Sunil Aggarwal’s legal battle to secure access to psilocybin for his terminal cancer patients.
Last Friday, the Oregon Health Authority (OHA) announced a temporary rule, effective immediately, that service centers may only authorize the “temporary use” of their space between the hours of 6am and 11:59pm local time. Currently, Oregon law allows service centers to “authorize the temporary use of the licensed premises for activities that are unrelated to the exercise of license privileges.” The current law also specifies that services centers can “sell psilocybin products and provide psilocybin services” between 6am and 11:59pm, but that doesn’t specifically apply to the “temporary use” of a space, meaning that, in theory, those spaces could operate beyond 11:59pm. The Microdose reached out to OHA to inquire about what “temporary use” might entail (overnight psilocybin sessions?) but did not hear back by the time we went to press. The new rule addresses what the state calls “an unintentional drafting error,” in its temporary administrative order, that could result in “a risk to public health and safety because they are more likely to involve intoxicated individuals that have consumed alcohol at neighboring businesses.” The order states that this could result in “theft, diversion, or consumption of regulated products” kept on site, as well as “disorderly conduct” and client information being at risk.
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