Psychedelics as preventive treatment in headache and chronic pain disorders.

The effects of psychedelic drugs in headache and chronic pain disorders have been reported for several decades, and now controlled studies are emerging. The existing evidence supports a lasting therapeutic benefit after limited dosing, a unique feature of the drug class that distinguishes it from conventional treatment. This commentary summarizes these reports of preventive effects of psychedelic drugs in headache and chronic pain disorders. The recently published controlled trial of psilocybin in migraine is reviewed, including its limitations. Several neurobiological targets of psychedelics that are related to headache and chronic pain are highlighted, though a clear separation of acute and lasting effects is key in uncovering the unique clinical effects of this drug class. Considerable investigation is required before the effects, safety, and mechanism of action of psychedelics in headache and chronic pain disorders can be known.