A Russian review names the limits of the psychedelic trial base
- A discussion article in Neurology Bulletin (2025;57(1):89–95) by Valentin Skryabin of the Russian Medical Academy of Continuous Professional Education, Moscow: a narrative review of 19 sources, with no data of its own, addressed to Russian psychiatrists.
- The review lists four limits of the research on psychedelic-assisted therapy: no adequate placebo, no standardized dosing, homogeneous samples, and psychotherapy built into trial designs.
- Mechanistic findings are mixed: 5-HT2A activation raises BDNF in the cortex and lowers it in the hippocampus, and 5-HT2B activation, associated with some of these compounds, has been linked to cardiovascular risk.
- The author concludes that the lack of high-quality evidence, methodological problems and unclear biological mechanisms call for a cautious approach, and calls the question of whether the effects are overestimated unresolved.
Valentin Skryabin, of the Russian Medical Academy of Continuous Professional Education in Moscow, wrote a discussion article for Neurology Bulletin on studies of compounds such as psilocybin and MDMA in depression, PTSD, anxiety and obsessive-compulsive disorders. It is a narrative review of 19 sources and reports no data of its own.
Four limits of the trials
Psychedelics produce vivid effects that are hard to mask. Niacin and diphenhydramine (Benadryl) as placebo proved insufficient, because participants recognize the missing effect; low doses are not a classical placebo either. Dosing is not standardized, which complicates replication and comparison between studies. Samples are homogeneous: many participants have prior experience, recruitment often runs through online communities, and most are middle-aged and of European descent. Nearly all trials include psychotherapy, which can change outcomes on its own, so the compound's effect is hard to separate from the therapy's.
Mechanisms and the label "new"
Findings on mechanisms conflict: 5-HT2A activation raises BDNF in the cortex and lowers it in the hippocampus. The REBUS model is, in the author's words, theoretical rather than mechanistic. He also notes that calling this therapy "new" risks repeating the missteps of the 1950s and 1960s.
When a client asks
A client who has read about these studies is asking where the research stands, and this article gives a specialist a sourced answer from a Russian journal: its author lists where the studies are hard to interpret and leaves the question open. The four limits turn into questions. How was the trial blinded? Do its participants resemble the person asking? How much of the result came with the psychotherapy that was part of the protocol? The review describes no method for clinical use, and this note does not either. It offers something narrower: a way to tell a client where the design limits lie, without steering the client toward or away from the topic.
The question of whether psychedelics represent a powerful therapeutic tool or if their effects are overestimated remains unresolved.
A narrative review of one author's opinion in a discussion section, with 19 sources and no data of its own. It is addressed to psychiatrists and describes research, not clinical practice.