I Study Cannabis and Psychedelics for a Living. It Still Doesn’t Fix My Migraines

Cannabis vs Psilocybin for Migraines

In college, I started smoking at parties. A joint passed in someone’s dorm room, a bowl before a show. Over time, the dynamic shifted. I stopped being the person who got smoked up and became the person who always had something to contribute.

By grad school, I was studying the brain — the chemistry of pain, motivation, and mood — and cannabis had moved indoors and inward. At the end of long days, I came home and decompressed with a plant that acted on many of the same systems I had spent the day analyzing. Now it is part of my daily work rhythm and my approach to stress and pain.

I also microdose psilocybin daily. Psilocybin is a natural compound found in Psilocybe mushrooms. Your body converts it into psilocin, which activates a specific serotonin receptor in the brain called the 5-HT2A receptor, producing its psychedelic and therapeutic effects. A microdose is about one-tenth of a recreational dose — no noticeable change in perception. I occasionally take a medium dose — below the range that produces a full psychedelic trip, calibrated to where I am on a given day.

Triptans for Migraines

In 2021, researchers at Yale ran the first controlled study of psilocybin as a migraine treatment. It was double-blind and crossover: each participant received psilocybin (0.143 mg/kg) in one session and a placebo in another, two weeks apart, so each served as their own control.

After psilocybin, participants had about 1.65 fewer migraine days per week on average. After the fake pill, they had 0.15 fewer. That difference was statistically significant (p=0.003).

The effects lasted beyond when the drug was active — up to two weeks after administration. The study had ten participants — far from definitive, but the first controlled design to test this directly, and the results were clear.

The pharmacological connection is worth naming. Triptans — the standard acute migraine medicines — work on serotonin receptors, specifically the 5-HT1B/1D subtype. Psilocybin works on the 5-HT2A subtype. Different subtypes, same serotonin family — the same system that migraine disrupts. This is part of why researchers think psilocybin’s migraine effect is pharmacologically grounded, with a mechanism that fits.

Battling Migraines as a Neuroscientist Who Studies Plant Medicines

I have a background in neuroscience — the study of the brain and nervous system. I can describe the exact mechanism by which CGRP triggers inflammation around the brain and why CB1 receptors cluster in the periaqueductal gray rather than in the cortex. I have spent time in laboratories studying the chemistry of pain, motivation, and mood — the same systems cannabis acts on, the same systems that govern migraine.

None of that knowledge answers the question I most want answered: whether cannabis is actually doing what I think it is doing for my own pain.

It is the specific problem of being a scientist who is also a patient — and who came to cannabis on a lawn in June, years before I had ever thought about experimental controls.

Picking Apart the Variables of a Migraine

I know what a causal claim requires. To show that A causes B, you have to control for everything else that varies. My personal experience does not meet that standard. I am a sample of one, unblinded, with no comparison group.

Effect size captures two things: whether an association exists, and how strong it is. I cannot separate the effect of cannabis from my sleep, my stress, whether I caught the attack early, or whether I had sparkling wine the night before. Those are confounding variables — things that affect the outcome but have not been controlled for. Cannabis and psilocybin both act on many of the same brain systems. Each can change how the other works. I cannot pull their effects apart.

One thing I know from the inside: when a migraine starts, and I reach for cannabis instead of sumatriptan, I am making a choice the current research cannot validate for me. It may be working through the CB1 mechanisms described here. It may be placebo. The honest answer is probably both, and I cannot tell which part is which.

I am also a woman, which adds a variable I cannot account for through self-observation. Migraine is two to three times more common in women than in men. Part of the reason is estrogen: the drop before menstruation is one of the most reliable migraine triggers known.

Research has found that estrogen levels also affect how actively the endocannabinoid system operates. Higher estrogen is linked to more CB1 receptor activity — the same receptor through which cannabis primarily works. My biology, my migraines, and my response to cannabis may not be fully separable from my hormonal profile.

Stress is the most commonly reported migraine trigger. Among patients who report having triggers, nearly 80% name stress as one. The mechanism is direct: stress hormones activate the trigeminal pain pathways and lower the threshold for an attack. CB1 receptor activity dampens the brain’s stress response.

That means when I say cannabis helps with stress and pain, those two things may not be separate at all. Reducing the stress response may be targeting the migraine trigger at the same time. I cannot measure that in my own experience. But it is biologically coherent. At best, what I have is a correlation.

The Research on Cannabis and Migraine Relief

The controlled research offers something cleaner. The biggest observational study on cannabis and migraine came from Carrie Cuttler’s team at Washington State University, published in 2020. They used Strainprint, a phone app that let medical cannabis patients log symptoms before and after use.

• Inhaled cannabis was linked to a 47.3% drop in headache pain and a 49.6% drop in migraine pain on average.
• Higher THC content was specifically associated with greater headache reduction.
• Men reported larger headache reductions than women.
• The role of CBD in migraine is much less clear.

The study found no evidence of medication overuse headache in the self-report data. Cuttler said the results were probably inflated — people who found no relief would stop logging — and called for controlled trials. The direction is real. The exact size is uncertain.

The Rebound Effect

The risk that rarely gets mentioned: using any pain medicine too often can cause more headaches. When the brain receives external pain relief regularly, it dials back its own pain-control activity over time. The system becomes less responsive. Doctors call this medication overuse headache, or MOH.

A 2021 Stanford study enrolled patients with chronic migraine — 15 or more migraine days per month for at least a year. Cannabis users were nearly six times more likely to have MOH (odds ratio 5.99; 95% CI 3.45–10.43).

The study was backward-looking — we cannot say which came first. But the link was clear. I track my headache frequency. I have read that paper more than once.