Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Several Cochrane Reviews look at interventions for palliative care. These were added to in September 2024 with the publication of a new review of psychedelic-assisted therapy. In this podcast, two of the authors, Sivan Schipper from Spital Uster and Christopher Boehlke from University Hospital Basel both in Switzerland, tell us about the treatment and the review’s findings.

Sivan: Hello Christopher. Let’s begin with a short introduction to psychedelic-assisted therapy. What is it and how is it used?

Christopher: Hello Sivan. Psychedelic-assisted therapy, PAT for short, uses psychedelic drugs such as psilocybin, LSD or MDMA to induce altered states of consciousness under therapeutic supervision. PAT has received much media attention due to several clinical trials suggesting its effectiveness for relieving common psychiatric conditions like depression or post-traumatic stress disorder. Importantly, PAT is conducted within preparatory therapeutic sessions before the psychedelic experience and the integrative therapeutic sessions.

Sivan: In our review, we looked at PAT’s use in people with life-threatening disease. Why might it be helpful in this setting?

Christopher: In palliative care, we try to ease the suffering of patients with serious, often terminal illnesses. This includes a combination of symptom management, psychological support, and other therapies. Anxiety, depression, and existential distress are frequently debilitating for people facing a life-threatening disease, but drug interventions have limited efficacy, especially at the end of life. There is an obvious need for new, more efficient, and faster-acting interventions in this population that does not have the luxury of time and promising early-phase clinical research (in the 1960s and early 1970s) suggested a therapeutic potential for psychedelics in treating cancer-related distress. However, this psychedelic research was halted for several reasons, but started again in the early 2000s as part of the so called ‘psychedelic renaissance’.

Sivan: Which leads us to the review, please can you say a few words about what we did, and why?

Christopher: We wanted to find out whether PAT could improve anxiety, depression, and existential distress and whether it was linked to any unwanted effects or hazards. We found some promising results, but there is an ongoing need for research to provide the strong evidence needed for this potentially important treatment.

Sivan: Let’s go into this a little deeper. What did we look for and what did we find?

Christopher: We searched for high-quality clinical studies investigating the use of LSD, psilocybin or MDMA in patients with a life-threatening disease to treat anxiety, depression, and existential distress. We found six studies, with three testing psilocybin, two testing LSD and one for MDMA -assisted therapy. These recruited a total of 149 adults and most studies had a follow-up of 6 to 12 months.

Sivan: And, what about the results?

Christopher: This currently available evidence base shows that PAT with the classic psychedelics, psilocybin and LSD, compared to (active) placebo may result in a reduction of anxiety and reduce depression. However, our confidence in the effect estimate is limited and it might change substantially when more studies are conducted. PAT with classical psychedelics may also reduce existential distress, but the evidence is very uncertain. For PAT with MDMA, the data on anxiety or depression is inconclusive; and the trial did not investigate existential distress. Overall, the drugs caused few and mild to moderate side effects, which subsided when the drug effects wore off or during the days after.

Sivan: Thanks Chistopher, perhaps you could finish by expanding on why we’re uncertain about the results, and how listeners can access the review

Christopher: Thanks Sivan. Our lack of confidence in the results arises from several limitations in the trials. Importantly, blinding procedures were mostly ineffective, with participants becoming aware of the treatment they were receiving, which may influence their recorded outcomes. In addition, the studies were small. Promisingly, though, we know of seven ongoing studies, that will add to the evidence base for PAT and these might change the conclusions of this review. Finally, to find the review, if people go to Cochrane Library dot com and search ‘psychedelic assisted therapy in life-threatening disease’, they’ll see the link to it.