Psychedelics in psychiatry: yesterday, today, and tomorrow?

In psychiatric therapy research, psychedelic-assisted psychotherapy is currently one of the most exciting areas of research. What trends could await us?

Psychedelics research: Psilocybin has been "leading the way"

As part of the INSIGHT Conference 2023, Prof. Dr. med. Gerhard Gründer presented in the session titled "Psychedelics in psychiatry: present and future". Prof. Gründer provided an overview of the most important psychedelics research of the past years as well as their study settings. He shared details on the framework conditions for clearer results, which are essential for approvals on a broader basis.

According to Prof. Gründer, a large part of modern clinical studies on psychedelics is related to the use of psilocybin. Currently (as 1 September, 2023) 149 different studies are listed. The main indications for treatment are MDD, therapy-resistant depression, or anxiety or depression at the end of life. Further application possibilities tested in studies according to Prof. Gründer are:

In some of these research areas, psilocybin has shown high statistical effect sizes, but however, as the physician points out, the study settings are also very small, which in turn quickly leads to high effect sizes.

Psychedelics in clinical trials: an overview

Some of the psilocybin studies were specifically cited by Prof. Gründer:

[Original citation in German, translated by the editor] Primary endpoint at 6 weeks, "insufficient statistical power" → 59 patients in study; mean QIDS-SR-16 scores at baseline were 14.5 in psilocybin group and 16.4 in escitalopram group. Mean (±SE) changes in scores from baseline to week 6 were -8.0±1.0 points in psilocybin group and -6.0±1.0 in escitalopram group; difference between groups of 2.0 points equals (95% confidence interval [CI], -5.0 to 0.9) (P=0.17).

[Original citation in German, translated by the editor] Psilocybin in unipolar depression, randomised controlled trial of 27 patients with MDD; 17 participants (71%) had clinically significant response to intervention (≥50% reduction in GRID-HAMD score) at week 1 and 17 (71%) at week 4; 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (GRID-HAMD score ≤7).

Prof. Gründer also presented the "EPIsoDE study" on the efficacy and safety of psilocybin in treatment-resistant unipolar depression, in which the speaker himself is involved. This is a randomised, bicentre, double-blind, active placebo-controlled parallel group study in phase II. In the study, participants are given psilocybin in two doses or a placebo. Participants will receive either a low (5mg) or high (25mg) dose, with a primary endpoint of 6 weeks. Subsequently, participants from the low-dose cohort will receive the high dose (25mg), subjects in the higher-dose cohort will receive either low dose (5mg) or again the high dose (25mg), secondary endpoint is at 12 weeks. First results are expected in early 2024, according to the founder.

The future of psychedelic-assisted psychotherapy: not without larger trial settings

So is there a future for psychedelic-assisted psychotherapy? According to Prof. Gründer, there certainly is, considering the large number of clinical studies, but in his view, it will be years before it is routinely used in clinical practice. On the one hand, this is due to official regulations, just look at the topic of cannabis legalisation. Prof. Gründer explained that medical research with psychedelics crucially needs larger study cohorts and longer study periods of at least six months. A last decisive criterion is that studies on psychedelic-assisted psychotherapy must also concretely prove that there is a better effect, when compared to compulsory therapy.

This article was translated from the original German version. For more information about the conference, you can access the INSIGHT 2023 site here.