End-of-Life Distress Research
What small randomized trials and a 2024 Cochrane review found for psilocybin, LSD and MDMA in anxiety, depression and existential distress with life-threatening illness, and why certainty is low.
Content last updated . This page has not been medically reviewed.
Quick answer
Small randomized trials in people with life-threatening illness, mostly cancer, found large reductions in anxiety and depression after one or two sessions of psilocybin with psychotherapy. A 2024 Cochrane review pooled six trials and rated the certainty of the evidence as low to very low. No psychedelic was found approved for this use in the sources read. This page describes research, not treatment advice. If you or someone you know is in crisis in the US, call or text 988, or call 911.Evidence labels: promising but limited (positive results from small trials), insufficient evidence (too few or too uncertain results), approved medicine (none found here).
The two best-known psilocybin trials
Both were published in the Journal of Psychopharmacology and used a crossover design, meaning people received the study drug and the comparison in sequence.| Trial | Participants and design | Main finding |
|---|---|---|
| Griffiths [1] | 51 patients with life-threatening cancer diagnoses and depression or anxiety symptoms; double-blind; a very low, placebo-like psilocybin amount vs a high amount; 6-month follow-up | High-dose psilocybin produced large decreases in clinician- and self-rated depressed mood and anxiety. About 80% showed clinically significant decreases at 6 months. |
| Ross [2] | 29 patients with cancer-related anxiety and depression; double-blind, niacin placebo; psychotherapy with both; primary outcomes at 7 weeks before crossover | Psilocybin produced immediate, substantial and sustained improvement; about 60 to 80% still showed clinically significant reductions at 6.5 months. |
Both reported that the intensity of a "mystical-type" experience was linked to the improvement. [1][2] That is an association within the trial, not proof of how it works. The amounts used were set by the study protocols and are not guidance.
The 2024 Cochrane review
Cochrane reviewers included six randomized trials with 149 participants (data analyzed for 140), aged 36 to 64, in outpatient settings in the USA and Switzerland. Two interventions were studied: classic psychedelics (psilocybin or LSD) and MDMA, each with preparatory and integration therapy. [3]| Question | Finding | Certainty |
|---|---|---|
| Anxiety, classic psychedelics vs active placebo | Reduction; STAI-Trait difference -8.41 points on a 20 to 80 scale (5 studies, 122 people) | Low |
| Depression, classic psychedelics | Reduction; BDI difference -4.92 on a 0 to 63 scale (4 studies, 112 people) | Low |
| Anxiety and depression, MDMA | Very uncertain; one study of 18 people | Very low |
| Existential distress (demoralization), classic psychedelics | One 28-person study favored psilocybin; other measures mixed | Very low |
[3]
The reviewers found no treatment-related serious adverse events. Common minor to moderate events for classic psychedelics were raised blood pressure, nausea, anxiety, emotional distress and psychotic-like symptoms; these subsided when drug effects wore off or within about a week. [3] Drug companies did not fund the studies, but funding came from organizations that promote psychedelic-assisted therapy. [3] Blinding could not be achieved in any of the six studies. [3]
How to read these results
- Small numbers. Under 150 people were studied across all six trials, so rare harms may be missed. [3]
- Unblinding and expectation. People can tell when they received a strong drug, which can raise expectation effects. The FDA says this should be measured and addressed. [4]
- Narrow settings. Trials used screened participants, trained staff and monitored sessions. This is not the same as using a substance elsewhere. See what psychedelic-assisted therapy is.
- Short follow-up. The longest follow-up in the two trials above was about 6 to 6.5 months. [1][2]
Label: promising but limited for psilocybin; insufficient evidence for MDMA in this setting. For the underlying compound, see the psilocybin guide. For how trials are judged, see how to read a psychedelic clinical trial.
Important
Serious illness changes how medicines act and interact. Anyone with cancer or another serious illness should talk with their care team before considering any research participation. This page does not advise anyone to stop or change treatment.Frequently asked questions
Is psilocybin approved for cancer-related anxiety?
No approval was found in the sources read. The Cochrane review notes psychedelics remain illegal in many countries and restricted for research in the US. [3]
How strong is the evidence?
Cochrane rated it low to very low certainty because of small samples and high risk of bias. [3]
Did participants have serious side effects?
The review found no treatment-related serious adverse events across six trials, with minor to moderate effects such as raised blood pressure, nausea and anxiety. [3]
Do the results apply to people outside a clinical trial?
Not necessarily. Trials used screening, support and monitoring, and NIDA says poor mental health outcomes may be more likely outside clinical use. [5]
References
- Griffiths RR et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. Read 2026-10-22.
- Ross S et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. Read 2026-10-22.
- Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database Syst Rev 2024. Read 2026-10-22.
- U.S. Food and Drug Administration. Psychedelic Drugs: Considerations for Clinical Investigations, guidance for industry. Page content current as of 07/13/2026 (guidance PDF: https://www.fda.gov/media/169694/download). Read 2026-10-22.
- National Institute on Drug Abuse. Psychedelic and Dissociative Drugs. Read 2026-10-22.