Follow-up Study Suggests Psilocybin Effective in Treating Major Depression for up to a Year

A 12-month follow-up study of psilocybin-assisted therapy for major depressive disorder (MDD) was published this week. The previous study gained a great deal of attention when it showed that psilocybin relieved MDD symptoms for up to a month (Davis et al., 2021).

In this follow-up study Johns Hopkins researchers observed durable antidepressant effects, “with treatment response and remission on par with what was observed at 1 week and 1 month post treatment,” according to co-author Natalie Gukasyan who shared an informative Twitter thread summarising the paper.

Additionally, no serious safety concerns were identified during the follow-up study.

However, during the 12-month follow-up period, around 42% of participants received psychotherapy outside of the study protocol and a third of patients began taking daily antidepressants (nearly identical to the proportion of participants in Carhart-Harris et al.’s 6-month figures, the authors note), making it difficult to parse out the magnitude of the effect of psilocybin-assisted therapy in this particular study.

Gukasyan provided the key takeaway:

“Overall, it’s encouraging that remission and treatment response remained high throughout the 12 month follow-up, but for some participants part of that sustained improvement was likely also driven by other forms of treatment.”

Psychedelic-Induced Perceptual Distortions Appearing in Clinical Research? A Look at the Supplemental Material

While many of us (this author included) are often only able to skim new research publications, we’re fortunate that some of our colleagues dig deeper. Our Pharmaceutical Advisor Michael Haichin can be counted among the latter group.

In the supplemental material to the journal article, the authors note that there was only one adverse event between the 2-week and 12-week follow-ups deemed to potentially be related to the administration of psilocybin:

“A participant reported a one-minute long episode of visual distortions about three months following her second psilocybin session. She described an experience lasting about one minute, during which a patterned floor appeared to be “popping out in 3D.” The experience was described as pleasurable, did not meet criteria for HPPD, and did not recur.”

It is noted that the participant in question had a viral respiratory illness around a month before psilocybin administration, with symptoms including tinnitus: a possible risk factor for hallucinogen persisting perception disorder [HPPD] identified by Halpern et al..

Why is this so interesting? Well, it appears to be “the first reported instance of a delayed perceptual distortion related to psychedelic use in a research setting in the modern era of clinical research with these drugs,” according to the authors.

Ed Prideaux – freelance journalist and Advocacy Lead at HPPD nonprofit Perception Restoration Foundation – wrote on HPPD in an October 2021 Bulletin, and posited:

“That HPPD has not appeared in psychedelic clinical trials suggests that aftercare, integration and other independent mental health problems (screened out in their recruitment) may provide independent risk factors.”

So, is this single, minute-long delayed perceptual distortion reported by a participant in the present study a suggestion that we may begin seeing such distortions appear in long-term follow-up studies of psychedelic-assisted therapies? 

Perhaps. But, it’s also worth noting that the criteria for HPPD were not met in this instance; the perceptual distortion did not recur; and, the participant did not find the experience troubling (in fact, they described it as “pleasurable”).

See page 3 of the supplemental material for more on this case.