Psychedelic therapeutic: Potential treatment for headache disorders.

This interesting free full-text paper notes "no single therapy is effective in all patients and a combination of treatments is often necessary to manage the disease, necessitating the continued search for new therapeutic avenues in headache disorders. Furthermore, there are many limitations of conventional therapy, including intolerable side effects, poor efficacy, lack of insurance coverage, and deficiencies in clinician knowledge, which invariably have driven patients to unconventional agents. In the past decade, reports suggest that psilocybin, lysergic acid diethylamide (LSD), and other indoleamine 5-hydroxytryptamine 5-HT2A receptor agonist compounds (Scheme 1) can sustain therapeutic benefit in cluster headache with reductions in headache burden after a single or few doses and in some cases may induce remission.  The nonhallucinogenic LSD derivative BOL-148 has been shown to suppress attacks in cluster headache, and only three single oral doses of 30 μg/kg BOL-148 were found to either break a cluster headache cycle or considerably improve the frequency and intensity of attacks. The mechanism by which psilocybin treats headache is currently unknown. Understanding the underlying mechanism causing headache disorders is crucial for the development of novel therapeutics and also to know which type of drug to prescribe to treat patients. Psilocybin is metabolized to psilocin, which is an agonist for serotonin receptors, and binds to 5-HT2A with high affinity and to 5-HT1 with low affinity. Psilocin can indirectly increase concentrations of dopamine and serotonin in the brain. Though LSD and psilocybin are used by individuals to treat headache, there has been no guarantee of the dosing or accuracy of the active substance, in addition to the lack of proper scientific observation or data gathering. This Patent Highlight presents a method of treating headache disorders that includes administering an effective amount of a composition of a psychedelic to the individual and treating the headache disorder with an effective therapeutic dose. There were no serious or unexpected adverse events reported in the study. However, transient nausea and anxiety were reported for acute psilocybin exposure."