Aims: A case report suggested the efficacy of cannabis to treat cluster headache (CH) attacks. Our aims were to study the frequency of cannabis use in CH patients, and the reported effects on attacks.
Methods: A total of 139 patients with CH attending two French headache centers filled out questionnaires.
Results: Sixty-three of the 139 patients (45.3%) had a history of cannabis use. As compared to nonusers, cannabis users were more likely to be younger (p < 0.001), male (p = 0.002) and tobacco smokers (p < 0.001). Among the 27 patients (19.4% of the total cohort) who had tried cannabis to treat CH attacks, 25.9% reported some efficacy, 51.8% variable or uncertain effects, and 22.3% negative effects.
The material presented was drawn from standard searches of the PubMed/National Library of Medicine database, influential sources of current medical literature, and past review articles. Search keywords included cannabis; cannabinoids; headache; migraine; cluster headache; medication-overuse headache; tetrahydrocannabinol; cannabidiol; clinical trial; placebo; and double blind. CliniacalTrials.gov was also queried for studies that have not yet been published. Individual articles were selected based on historical, clinical, or preclinical relevance to cannabinoids or cannabis as a treatment for headaches.
One such option, cannabis, has been ignored in the United States for the past several decades but has an established history in the treatment of headaches. Assyrian manuscripts from the second millennium BCE recommended cannabis to “bind the temples,” 18 and Ayurvedic preparations in the third and fourth centuries BCE were indicated for “diseases of the head” such as migraines. 19 The prescription of cannabis was even recommended in ancient Greece, with Pedanius Dioscorides describing its use in his De Maternia Medica as a treatment for “pain of the ears.” 20 Other citations documenting the use of cannabis for headache disorders arise from the ninth century in the Al-Aq-rabadhin Al-Saghir, the earliest known document of Arabic pharmacology. 19 Further recommendations are found in Persian texts from the 10th 21 and 17th centuries. 22 Prominent physicians of the Middle Ages, including John Parkinson 23 and Nicholas Culpeper, 24 also recommended the use of cannabis for headache.
Historical Use of Cannabis for Headache
MS, multiple sclerosis.
Reports from 139 cluster headache patients 56 indicate that cannabis could have value in treating a portion (25.9%) of these patients as well. However, cannabis was reported to provoke cluster headache attacks in some patients (22.4%) as well. One possible explanation for this provoking effect is that cannabis is known to increase heart rate, increase blood pressure, and cause systemic vasodilation. 67 Cluster headache sufferers seem to be highly sensitive to vasodilation of the carotid tree and increased oxygen demands, findings that are supported by evidence that alcohol is a reliable trigger and supplemental oxygen is an effective abortive therapy. 68 The increased oxygen demand and/or the vasodilation effects of cannabis could theoretically be responsible for this exacerbation in some cluster headache sufferers. Interestingly, cluster headaches appear to show improvement with treatment using hallucinogens such as d-lysergic acid amide (ergine or LSA), psilocybin, and lysergic acid diethylamide (LSD). 33 As such, it is possible that the psychoactive properties of THC could play a role in the treatment of cluster headaches.
Materials and Methods
The present review has four unique aims: (1) Highlight common historical trends in the use of cannabis in the treatment of headache to inform future clinical guidelines. (2) Briefly present the current clinical literature on this topic, with a focus on more recent publications that have not been discussed in past reviews. (3) Compile various preclinical studies into a prospective integrated model outlining the role of cannabinoids in the modulation of headache pathogenesis. (4) Outline several 19,32–35 future directions that warrant exploration based on the limited, but promising findings on this topic.