Psychedelics on the verge of FDA approval, Part 1: Synthetic Psilocybin for depression
The Trump administration recently issued an Executive Order to expedite the availability of psychedelic medications. As I reported for The Guardian, this order's significance was largely symbolic, according to Dr. Mason Marks, a Florida State University professor and senior fellow at Harvard Law School who focuses on psychedelic law.
One of the reasons the order is mostly symbolic is because the FDA has already shown itself to be quite open to psychedelic treatments, and several show promise for FDA approval within 1-3 years, according to Marks. I'm going to make a post about each of the treatments that could be up for approval soon. The furthest along is COMP360 Psilocybin for treatment resistant depression.
Who is the sponsor?
•Compass Pathways describes itself as a "biotechnology company."
•Based on their website, their focus is almost entirely on psilocybin treatment for different conditions, including anorexia and PTSD as well as depression.
•They are publicly traded on NASDAQ since 2020
•Peter Thiel, controversial for cofounding Palantir, which now provides AI technology to ICE, is one of their backers.
•Sting is also an investor.
What is the drug?
COMP360 Psilocybin is a synthetic, proprietary formulation of psilocybin, specifically formulated for treatment-resistant depression.
How effective is it?
•After taking a single 25 mg dose of COMP360 psilocybin, only 29% of patients experienced remission and only 37% experienced any relief at all from their depression symptoms three weeks after receiving the dose.
•These numbers come from a phase 2 trial of COMP360 psilocybin, intended in part to establish the best dose of the drug. The 25 mg dose performed far better than 10 mg and 1 mg doses.
•Participants in each different dose group reported suicidal behaviors during the trial.
•Preliminary results from an ongoing phase 3 trial found that 39% of participants who received two 25 mg doses of COMP360 experienced a meaningful reduction in symptoms—a slightly better result.
How did the researchers measure depression?
•They used the Montgomery-Asberg Depression Rating Scale (MADRS) as their primary measure to assess participants' depression levels at baseline and three weeks after receiving the dose.
•MADRS scores depression levels using these factors: Apparent Sadness; Reported Sadness; Inner tension; Reduced sleep; Reduced appetite; Concentration difficulties; Lassitude (hard time getting started with and performing everyday activities); Inability to feel; Pessimistic thoughts; Suicidal thoughts.
•Each of these 10 factors can be scored between 0 to 6, where 6 reflects the worst symptoms. Scores can range from 0-60, and a score above 34 is considered "severe depression."
•Remission from depression is defined as a MADRS total score of less than or equal to 10.
What to make of these relatively low recovery numbers?
•These patients all had treatment resistant depression, and had already tried at least two other medications in the past, so it's possible that the severity of their condition contributed to COMP360 psilocybin's somewhat underwhelming performance.
• Dr. Marks had this to say about it:
I can understand why some people might have expected a more dramatic effect. But from my perspective, I think you have to compare the psilocybin results to the current treatments, which are drugs you take every single day, like Prozac or Paxil. They have a lot of undesirable side effects. So if you can take a drug twice in six weeks, even if the effect is no better, you may have less weight gain, less insomnia, fewer sexual side effects. So I think some people look at the antidepressant effect [of COMP360 psilocybin] and say, 'Oh, it should have been much higher.' But I think you kind of have to take a holistic view and say, 'Well, you know, these are very different treatments. This might work better for some people.'
Could natural psilocybin work better?
•Pharmaceutical companies often prefer synthetic compounds to botanical compounds. It's easier to standardize synthetic doses, and the FDA has only approved a tiny, tiny fraction of botanical drug applications.
•An open label trial of a single dose of mushroom derived psilocybin, published in The Lancet found the dose facilitated lasting improvement in depression symptoms in all 12 participants. These patients also had treatment resistant depression. It's worth noting that this trial was small, and that the placebo effect may have played a bigger role in this study than in the COMP360 studies, given that participants knew they were all receiving the same dose.
•Molecular research has suggested that botanical psilocybin can have something akin to the "entourage effect" that comes with whole-plant cannabis, where the full experience a plant can provide is greater than the sum of its parts. In other words, the full effect of magic mushrooms might come from all the combined compounds in the mushroom, not just psilocybin. These complex effects can be difficult to isolate and synthesize.
Will COMP360 psilocybin likely get FDA approval?
Many commenters think the answer is yes. These include Dr. Marks, as well as Dr. Sandeep Nayak of Johns Hopkins Center for Psychedelic & Consciousness Research.
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