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Yale Research on Psychedelics Gives Hope to Headache Disorder Community

March 13, 2023
by Allison Greco

Throughout the twentieth century, clinical research on the therapeutic effects of psychedelics has largely focused on psychiatric disorders. These same effects have also been reported in relation to headache disorders, but research has been limited.

Medical Director of the Headache Center of Excellence at the West Haven VA Medical Center and Assistant Professor of Neurology Emmanuelle Schindler, MD, PhD seeks to change that.

Psychedelics are defined as agonists at the 5-hydroxytryptamine (5-HT, serotonin) 2A receptor that acutely cause alterations in sensation, perception, and consciousness. They include drugs such as psilocybin (the psychoactive component in Psilocybe “magic” mushrooms), lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT), as well as phenethylamines such as mescaline.

Beginning in the 1950s, research on psychedelics – mainly LSD – as potential treatments for psychiatric disorders, substance abuse, and end-of-life distress dominated the landscape, overshadowing the early evidence for therapeutic effects of psychedelics and headache disorders.

Schindler’s path to studying psychedelics began in graduate school, where she investigated the pharmacology of these drugs. Later, her expertise in this area merged with her clinical interest in headache disorders. She currently studies the therapeutic effects of psilocybin, and she is believed to be the only researcher in the United States studying psychedelics in headache disorders. She is also the first to study any psychedelic in humans at Yale. She collaborates with Deepak Cyril Dsouza, MBBS, MD from Yale Psychiatry and Chris Gottschalk, MD from Yale Neurology for her research. Her studies are funded by Ceruvia Lifesciences and the Wallace Research Foundation.

“Headache disorders are decades long, and so true [management] of the disorder doesn’t take place during a short research study,” says Schindler. “I’m currently investigating whether there is a therapeutic effect on the headache disorder…how to optimize this effect…and where the effect is coming from.”

Most modern research has focused on therapeutic effects in cluster headache, a severe condition also known as “suicide headache,” as well as in migraine and post-traumatic headache, the latter of which is common among veterans. Schindler notes that although the mechanistic role that psychedelics play in reducing the burden of these headache disorders is unknown, it is necessary – and logical – to pursue research that studies their positive effects. "Psilocybin and other psychedelics such as LSD are chemically and pharmacologically similar to existing headache medications," she says. "[To] think that they have effects in headache disorders is not a stretch, though they do have the unique ability to produce lasting effects after a single dose.”

In conducting her research, Schindler collaborates with Clusterbusters, Inc., a research, education, and support hub for people suffering from cluster headache. The non-profit was founded by Executive Director and Founder Bob Wold in 2002 after he connected with fellow cluster headache sufferers and grew frustrated with the lack of research and treatment options available.

“When we stumbled upon a new possible treatment that was showing promise among our membership, I decided that we needed to get research underway. Since the medical community wasn't showing us any signs of finding something, I decided it was up to me,” says Wold.

Engaging the medical community has proved instrumental in the decades since Clusterbusters’s founding. Not only is there a greater recognition of the hallmark radiating temple, eye, and tooth pain of a cluster headache attack, but there have also been significant research collaborations with Yale on psychedelics, given that many patients self-manage and report long-lasting effects after very limited drug dosing.

“The advancement of the psychedelic research has been instrumental in also advancing the education of the medical community regarding cluster headache in general. We have also partnered on additional research studies looking at the state of efficacy of conventional treatments, suicidality, and pain,” said Wold.

Educating the medical community and participation in research ultimately gives hope to an often isolated and misunderstood patient population.

“The most important thing Clusterbusters does is give support and hope,” said Board President and Event Coordinator Eileen Brewer. “We are bringing this community together, and the community includes those with cluster headache, their care partners, their healthcare providers, and the researchers working to find treatments for this devastating disease.”

Even with such promising advances in the last few decades, the next phase in the fight against headache disorders will be to prove the safety and efficacy of psychedelics as valid therapeutics through continued research and preclinical data.

According to Schindler, psychedelics do have the potential to cause side effects such as seizures and manic and psychotic episodes, which need to be carefully considered. Furthermore, psychedelics are not currently approved for legal use by either the Drug Enforcement Administration (DEA) or Food and Drug Administration (FDA), and a consistent model for insurance coverage needs to be established.

The road to total decriminalization and destigmatization in the United States may be long, but with each study that is conducted on the function and effects of psychedelics, researchers like Schindler will continue to provide hope and alleviate the suffering of a community that has been searching for answers.

Submitted by Allison Greco on March 13, 2023