Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin

Abstract

While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT 2A ) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test sessions spaced 2 weeks apart. Subjects maintained headache diaries starting 2 weeks before the first session until 2 weeks after the second session. Physiological and psychological drug effects were monitored during sessions and several follow-up contacts with subjects were carried out to assure safety of study procedures. Ten subjects were included in the final analysis. Over the 2-week period measured after single administration, the reduction in weekly migraine days from baseline was significantly greater after psilocybin (mean, − 1.65 (95% CI: − 2.53 to − 0.77) days/week) than after placebo (− 0.15 (− 1.13 to 0.83) days/week; p = 0.003, t(9) = 4.11). Changes in migraine frequency in the 2 weeks after psilocybin were not correlated with the intensity of acute psychotropic effects during drug administration. Psilocybin was well-tolerated; there were no unexpected or serious adverse events or withdrawals due to adverse events. This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin. The separation of acute psychotropic effects and lasting therapeutic effects is an important finding, urging further investigation into the mechanism underlying the clinical effects of select 5-HT 2A receptor compounds in migraine, as well as other neuropsychiatric conditions. Clinicaltrials.gov: NCT03341689

Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports

“…After more than 6 decades of research into and popular use of classic psychedelics (defined here as a class of drugs that produce a unique profile of subjective effects and have a principal site of action at the 5HT 2A receptor, such as LSD or psilocybin), recent promising trials investigating the effects of psilocybin therapy for the treatment of depression [1,2], anxiety and depression in cancer patients [3,4], tobacco smoking [5], and alcohol use disorder [6] have inspired additional medical, commercial, and public interest in using psychedelics as treatments for psychiatric disorders. Interest has also grown in understanding whether psilocybin therapy may be effective for a wider range of indications [7][8][9].…”

Psychedelic perceptions: mental health service user attitudes to psilocybin therapy

“…Preliminary clinical evidence suggests that the synergistic combination of psychedelic compounds with psychological support may improve outcomes in major depressive disorder (MDD) [ 3 , 4 ], treatment-resistant depression (TRD) [ 5 , 6 ], and addiction disorders [ 7 – 10 ]. Exploratory studies suggest potential benefits of psilocybin therapy in OCD [ 11 ], eating disorders [ 12 ], and migraine suppression [ 13 ], with ongoing clinical trials of psychedelic therapy in MDD, TRD, bipolar disorder type II depression, anxiety, alcohol use disorder, smoking cessation, cocaine addiction, anorexia nervosa, depression with mild cognitive impairment, OCD, and various types of headaches [ 14 ]. Results from ongoing well-powered double-blind randomized controlled trials (RCTs) will determine whether psychedelic therapy translates into clinical benefits for non-psychotic disorders in clinical psychiatry.…”

Potencial terapéutico de los alucinógenos en las cefaleas: una revisión teórica

“…Con respecto a la psilocibina, los pacientes con migraña y con cefalea en racimos la han considerado eficaz a través de encuestas (Sewell et al, 2006;Schindler et al, 2015;Andersson et al, 2017) y en los estudios de caso único (Sewell et al, 2006;Sempere, 2016), así como también demostró eficacia en una reciente investigación controlada con placebo (Schindler et al, 2020). Habitualmente, se ha administrado eficazmente tanto para abortar el ataque como para prevenirlo.…”

“…Habitualmente, se ha administrado eficazmente tanto para abortar el ataque como para prevenirlo. Estos alentadores resultados contrastan con algunas investigaciones en las que el dolor de cabeza apareció como efecto secundario en voluntarios sanos tras la administración de psilocibina (Griffiths et al, 2006;Griffiths et al, 2008;Johnson et al 2012), aunque la cefalea se calificó como leve o moderada y de carácter transitorio, al igual que ocurrió en un estudio con pacientes con migraña (Schindler et al, 2020).…”

“…Por otra parte, el mecanismo de acción responsable de la eficacia de las sustancias mencionadas no está claro. En cuanto a las indolaminas consideradas (psilocibina y LSD), se ha planteado que su acción agonista a los receptores 5-HT 2A podría estar mediando los efectos clínicos sobre la migraña (Sewell, 2020), en consonancia con los resultados obtenidos en estudios con modelos animales, donde se ha constatado que la activación de dichos receptores provoca efectos antiinflamatorios (Flanagan & Nichols, 2018). Las alteraciones en el sueño se encuentran bajo investigación, pero puede formar parte de la fisiopatología de las cefaleas, donde los receptores 5-HT 2A también muestran su implicación, por lo que podría estar relacionado con el potencial terapéutico de estas sustancias (Schindler et al, 2018).…”