At the moment, the U.S. Food and Drug Administration (FDA) has not approved psychedelics for treating neurologic disorders or any other conditions, other than in approved clinical trials—which are rigorously monitored to ensure safety as well as the purity of the psychedelics. Most of the research to date has focused on mental health disorders, and the FDA's recent draft guidance on using psychedelics in trials is geared toward those types of studies.

A few small studies have tested psychedelics such as lysergic acid diethylamide (LSD) and psilocybin (“magic mushrooms”) for treating migraine and cluster headache, but results are considered preliminary. An exploratory trial of psilocybin for cluster headache published in the journal Headache in 2022 did not support its overall effectiveness, possibly due to the small number of participants, but found that it was safe and well tolerated. However, for those with chronic attacks, the therapeutic effect of psilocybin lasted the full eight weeks of the study.

Several studies are looking at LSD for cluster headache as well. For treating migraine, one small clinical trial, published in Neurotherapeutics in 2021, showed that a low dose of psilocybin can have therapeutic effects for at least two weeks. The researchers also noted a separation of acute psychotropic effects and persistent therapeutic effects.

Because clinical trials are just beginning, no strong body of evidence supports their use for migraine or cluster headache. Since the early 2000s, people with cluster headache—a condition that involves attacks of excruciating pain in or around the eye on one side of the head that can occur up to eight times a day for weeks, months, or years—have reported through surveys and case studies that one or several low doses of psilocybin or LSD can provide relief for weeks or months. So far, only anecdotal reports exist of people finding relief for other headache and facial pain disorders, such as new daily persistent headache and trigeminal neuralgia.

For cluster headache disorders, psychedelics have been studied as a transitional treatment—one to three doses, taken over a short period of time (one to two weeks), that have effects that can last as long as several months. This is similar to other transitional headache treatments such as steroid pulses or occipital nerve blocks, which are used to address severe attacks until a longer-lasting treatment is initiated. While psychedelics might stop a single headache attack, they are not a practical treatment, particularly for people with cluster headache who have multiple daily attacks.

Scientists don't yet know the mechanism that makes some psychedelics—which acutely cause changes in sensation, perception, and consciousness by activating the brain's serotonin receptors—effective for certain neurologic conditions. In clinical trials, psilocybin and LSD are taken orally. Mescaline, which is found in cacti and can be manufactured synthetically, is not studied much.

As far back as the 1960s, research has been done on psychedelics for cancer pain and phantom limb pain (when the brain continues processing pain signals after an amputation). There are even a few case reports on using psychedelics for back pain.

Not everyone is eligible to participate in clinical trials on psychedelics. Because the drugs activate the cardiovascular and cerebrovascular systems and could lead to a heart attack or stroke, people with uncontrolled high blood pressure or who have had a heart attack or stroke would be disqualified. The same is true for people with bipolar disease and schizophrenia, since psychedelics can aggravate or precipitate manic and psychotic symptoms.

If you find a clinical trial at ClinicalTrials.gov that is testing the use of psychedelics for neurologic conditions, consult with your doctor first to see if you would be eligible. And keep in mind that these studies may focus on treating mental health in a neurologic disorder and not directly target the disease itself.

Dr. Schindler is assistant professor at the Yale School of Medicine and medical director of the Headache Center of Excellence at VA Connecticut Healthcare System in West Haven.