People with cluster headache have been using psilocybin mushrooms to treat their symptoms for many years. A new preliminary study explores the effect of psilocybin on cluster headache and creates a foundation for future research on psychedelics and headache disorders.

For over 20 years, the psychedelic mushroom psilocybin has been used by people living with cluster headache to treat head pain and headache frequency. Psilocybin has never been officially recognized as a treatment for cluster headache—however, many in the cluster headache community have reported that, when taken in low doses (called “microdosing”), psilocybin mushrooms can alleviate pain and reduce the frequency of attacks.

In recent years, there has been renewed interest in researching psychedelics like psilocybin for treating a range of diseases and disorders, including anxiety, depression, addiction, PTSD and others. Now, a team of researchers has conducted the first ever randomized controlled trial to document the effects of psilocybin (derived from certain mushrooms) on cluster headache. In a preliminary study published in Headache, the research team confirmed that in some cases psilocybin mushrooms can relieve cluster headache pain and reduce the frequency of attacks—effects that have up until now only been self-reported by the cluster headache community.

To gain more insight into psilocybin’s potential effects on cluster headache, we spoke with the lead researcher of the study, Dr. Emmanuelle Schindler, Medical Director of the Headache Center of Excellence in West Haven, CT, and Assistant Professor of Neurology at Yale School of Medicine. Dr. Schindler explained what the results tell us about psilocybin and cluster headache, as well as how this first-of-its-kind study laid the groundwork for researchers to investigate psilocybin as a potential therapeutic for cluster headache in the future.

Evaluating Psilocybin’s Effect on Cluster Headache

According to Dr. Schindler, psychedelics are “chemically and pharmacologically very similar to existing conventional headache medications.” Psilocybin has been reported to reduce pain and other symptoms of cluster headache after a single or a few doses. In rare cases, it may even lead to complete remission.

Dr. Schindler and her team conducted “a proof of concept study” to further evaluate the effectiveness of psilocybin on cluster headache. Researchers gathered information from non-participating cluster headache patients about their own experiences and treatment regimens before the study began. They then identified a small sample group of 14 participants for the study itself.

Dr. Schindler emphasizes the importance of screening and selecting participants for this type of study with safety and psychological and emotional wellbeing at top of mind. “We didn’t have any serious adverse events or unexpected adverse events, but that was [because] patients were screened thoroughly, and medical and psychiatric backgrounds met all the criteria,” she says. “So, when done under those conditions, it was safe.”

After selection , the participants were given a low dose of psilocybin, taken three different times with approximately five days in between each dose. Researchers found that this regimen successfully alleviated headache pain and/or frequency for some patients but not for others. Due to the low number of participants, researchers could not reach any conclusions that psilocybin was effective for the treatment of cluster headache. Thus it was a negative study. The study also did not disprove that psilocybin was an effective treatment.

Promising Discoveries for Psilocybin as a Treatment

Though the study could not reach a definite conclusion, it still confirmed some key things that cluster headache patients who have used psilocybin have reported in the past. First, only some people respond to psilocybin as a treatment.

“Just like any other medication, it’s going to work for some people and not for others,” says Dr. Schindler. “And that was very clear in this study. There are some people who responded and had a dramatic reduction in their headache attack frequency and others that didn’t budge. No headache medication works for everybody.”

Psilocybin also shows promise as a valuable tool for deepening our understanding of cluster headache. “It’s so unique in that you can give a single dose and have a lasting effect on the disease,” explains Dr. Schindler. Researchers hope that future studies can help clarify the therapeutic mechanism behind this long-lasting effect in the interest of developing more effective treatments.

Researchers also discovered that for those who found the psilocybin treatments effective, the degree of symptom and pain relief was not directly related to the strength or intensity of the psychedelic experience. This indicates that “the mechanism [of cluster headache] is probably not directly related to the psychedelic experience itself,” says Dr. Schindler. “That’s in contrast to most studies in psychiatry [involving psilocybin], where the bigger your experience is on the test day, the greater your improvement weeks and months down the line.”

The Future of Psilocybin Research for Cluster Headache

Psilocybin shows potential as an effective treatment for cluster headache, but future research will need to deal with some specific challenges.

One of the clear next steps is to use larger sample sizes when conducting future studies. “We need a lot more patients,” advises Dr. Schindler. “It’s hard to make conclusions and to reach significance when you have small numbers.”

She also encourages future researchers to include multiple rounds of treatment, just as she and her team did with this study. “I invited patients back for a second round, because in headache medicine, you often have to wait for a medication to start working,” recalls Dr. Schindler. “The first round may not work; you have to do two or three rounds before you really get to see the effect. People who didn’t respond in the first portion—will they respond now after getting a second dose?” Having multiple scheduled rounds of treatment will help researchers more accurately evaluate psilocybin’s effects over time.

Why Preliminary Research Is Pivotal for Patients

Psilocybin has never been explored in a controlled study before, but Dr. Schindler hopes preliminary studies like this one will encourage investigative curiosity across the field. Even though this study yielded no conclusions, it is helping researchers take the first step toward finding new treatments for patients who live with migraine and headache disorders that currently have no cure.

“Doing the randomized controlled trial was a necessary step to go forward to investigate the drug,” says Dr. Schindler. “And I can’t do it all. I need help. So, we also need other groups to be interested and to do the research as well.”

While the effects of psilocybin are still being investigated, this study confirmed that it has potential as a treatment option. Additional studies will create more opportunities to learn so that doctors can offer better, more individualized treatments in the future. Until further large-scale studies are conducted and this treatment receives an FDA approval, it is recommended that psilocybin therapy only be used in a clinical trial setting.

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