Pain and Headache-Related Research

What this page is

Some people with cluster headache and migraine have reported on their own that small amounts of psilocybin-containing mushrooms eased their attacks. Researchers have started to test this carefully. This page reports those tests, including the ones that did not reach their goal. It is not advice to treat pain or headache with a psychedelic. Cluster headache and migraine are managed by clinicians, and the safest next step for new or worsening head pain is a medical visit. Evidence labels: promising but limited, mixed, insufficient evidence, no good evidence of benefit and Proper evidence not found.

Cluster headache

Cluster headache is a headache disorder with repeated attacks. Before 2022, sustained benefit after a limited amount of psilocybin-containing mushrooms was reported only anecdotally, and no controlled studies existed. [1]

Randomized trial (2022). Sixteen people were randomized to psilocybin and 14 were included in the final analysis, compared with a placebo, in a pulse of three doses about 5 days apart. [1] Attack frequency fell by 3.2 per week with psilocybin versus almost no change with placebo, but the difference was not statistically significant (p = 0.251). [1] The authors state the efficacy outcomes were negative, partly because so few people took part. [1] A larger effect was seen among people with chronic cluster headache (an exploratory subgroup), and changes in attacks did not track how strong the acute psychedelic effects were. [1] No unexpected or serious adverse events were reported. [1]

Repeat round (2024). Ten of the participants returned at least six months later for a blinded extension. Attacks fell from 18.4 to 9.8 per week (p = 0.013). [2] This extension had no separate placebo group described in the abstract, so it is a before-and-after result. The authors call for larger and more representative samples. [2]

Label: promising but limited. The primary result of the only randomized trial was not significant.

Migraine

A 2026 exploratory trial gave 18 adults with frequent migraine either zero, one or two doses of psilocybin, using diphenhydramine as the comparison drug. [3] Migraine days fell in every group, by about half, and the differences between groups were not significant. [3] The authors note that blinding was incomplete and that diphenhydramine only partly mimicked psilocybin's acute effects. [3] No serious or unexpected adverse events occurred. [3]

That pattern is a caution: when a comparison treatment also leads to large improvement, a drop in symptoms after psilocybin cannot be credited to psilocybin alone. Label: insufficient evidence.

Chronic and neuropathic pain

A 2025 systematic review of psilocybin for chronic neuropathic pain found 28 studies, and 76.2% were of low or very low quality. [4] The authors judge the overall evidence quality low, while saying results suggest promise. [4] A 2022 review chapter describes decades of anecdotal and early investigational reports that paved the way for the first controlled studies of psilocybin and LSD in these disorders. [5] Label: insufficient evidence.

LSD and pain

In a placebo-controlled study of healthy volunteers, repeated very small LSD amounts (15 micrograms, the study amount) did not produce pain-relief effects on a cold-water pain test overall. [6] A post hoc look at a smaller subgroup suggested a marginal effect, which the authors treat with caution. [6] Healthy volunteers are not people living with chronic pain. Label: no good evidence of benefit in this study.

Proper evidence not found

We searched PubMed on 2026-10-22 for randomized controlled trials of LSD in cluster headache or migraine and for large, controlled trials of psilocybin in chronic pain. We found reviews and the studies above, but no completed controlled trial of LSD in a headache disorder. [5]

Safety notes

The trials above were small research studies. They do not show safety outside research settings. For how psychoactive substances can interact with medicines, see psychedelic drug interactions. For a comparison with another substance studied for pain, see cannabis and cannabinoids for chronic pain. To read study design caveats, see how to read a psychedelic clinical trial and the psilocybin guide.