Headache The Journal of Head and Face Pain
November 1, 2022
Christina Luddy, Yutong Zhu, Hayley Lindsey et al.
75 citations
In an exploratory randomized, double-blind, placebo-controlled trial, a pulse regimen of three doses of psilocybin (0.143 mg/kg) given about five days apart did not significantly reduce cluster headache attack frequency compared to placebo. Over three weeks, attack frequency changed by −3.2 attacks per week with psilocybin (baseline 9.6) and 0.03 attacks per week with placebo (baseline 8.9), a difference that was not statistically significant. The overall effect size was moderate (d = 0.69), but large in chronic participants (d = 1.25) and small in episodic participants (d = 0.35). Changes in attack frequency were not linked to the intensity of acute psychedelic effects. Psilocybin was well-tolerated with no serious adverse events.
Headache The Journal of Head and Face Pain
February 25, 2011
Christina Sun‐edelstein, Alexander Mauskop
71 citations
A growing body of evidence supports the efficacy of various complementary and alternative medicine approaches for managing headache disorders. Nutraceutical options include vitamins and supplements (magnesium, riboflavin, coenzyme Q10, alpha lipoic acid) and herbal preparations (feverfew, butterbur). Some reports demonstrate the benefit of recreational drugs such as marijuana, LSD, and psilocybin, though this is controversial. Behavioral treatments include cognitive behavioral therapy and biobehavioral training (biofeedback, relaxation training). Physical treatments include acupuncture, oxygen therapy, transcutaneous electrical nerve stimulation, occlusal adjustment, cervical manipulation, physical therapy, massage, chiropractic therapy, and osteopathic manipulation. This review discusses the available evidence for all these treatments.
Headache The Journal of Head and Face Pain
July 1, 1977
M Fanciullacci, E. Del Bene, G Franchi et al.
30 citations
Oral treatment with sub-hallucinogenic doses of lysergic acid diethylamide (LSD-25) improved phantom limb pain in five of seven patients, with two showing striking improvement and three moderate reduction in pain and analgesic use; two patients experienced no benefit. Intravenous infusion or bolus injection of LSD-25 at 10 ng/ml at 0.5 ml/min facilitated 5-HT venospasm. The findings suggest LSD-25 facilitates 5-HT activity centrally, consistent with the hypothesis that phantom limb pain has a central origin.
Headache The Journal of Head and Face Pain
January 1, 2024
Anja Sofie Petersen, Inger Marie Sørensen, Harald Schiønning et al.
29 citations
In a small open-label trial, ten people with chronic cluster headache received three doses of psilocybin (0.14 mg/kg) over three weeks. Attack frequency dropped by an average of 31% from the four-week baseline to the four-week follow-up, and one patient had 21 weeks of complete remission. Changes in hypothalamic–diencephalic functional connectivity correlated negatively with the reduction in attack frequency, suggesting this neural pathway may be involved in the treatment response. The treatment was well tolerated. The results indicate psilocybin may have prophylactic potential for chronic cluster headache, though larger controlled studies are needed.
Headache The Journal of Head and Face Pain
September 20, 2024
James Rucker, Sadie Hambleton, Catherine Bird et al.
12 citations
A small open-label trial tested low doses of psilocybin (5, 7.5, and 10 mg) with psychological support in four patients with chronic short-lasting unilateral neuralgiform headache attacks (SUNHA), a severe headache disorder. The study was terminated early due to recruitment difficulties; three participants completed all sessions. No significant adverse events occurred. Cognitive testing during the acute drug experience was not possible because participants reported high subjective dose intensity. Headache impact remained severe throughout the trial. Mean daily attack frequency decreased by more than 50% in two participants at final follow-up. Thematic analysis of clinical notes suggested psychological insights, including reconfigured relationships to headache pain, were key features of participants' experience. The clinical results provide no conclusive evidence for psilocybin in SUNHA.
Headache The Journal of Head and Face Pain
May 1, 2024
Jonathan A. Leighton, Cyril Petignat, Brian E. Mcgeeney
2 citations
A patient with SUNCT, a severe headache disorder causing intense, short-lived pain, found that ayahuasca—a psychoactive brew traditionally used by South American indigenous groups—completely stopped their attacks after other treatments had failed. Inhaled DMT, the main psychoactive ingredient in ayahuasca, and a strong dose of LSD also temporarily eliminated symptoms. This case suggests that serotonergic psychedelics may offer a new avenue for treating SUNCT and similar headache conditions.
Headache The Journal of Head and Face Pain
December 29, 2025
Emmanuelle A. D. Schindler, Christopher Gottschalk, Brian P. Pittman et al.
1 citation
In an exploratory randomized, double-blind, placebo-controlled trial, adults with migraine received either two doses of diphenhydramine placebo, one dose of psilocybin (10 mg) plus one dose of diphenhydramine, or two doses of psilocybin, each separated by 7 days. Over the two weeks after the sessions, the reduction in migraine days per week did not differ significantly among groups, though large effect sizes were seen for those receiving psilocybin. Over eight weeks, all groups showed similar reductions in migraine frequency of about 50%. Diphenhydramine partially mimicked psilocybin's acute effects, but blinding was incomplete. No serious adverse events occurred.