Methods: A total of 139 patients with CH attending two French headache centers filled out questionnaires.
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.
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.
Conclusions: Cannabis use is very frequent in CH patients, but its efficacy for the treatment of the attacks is limited. Less than one third of self-reported users mention a relief of their attacks following inhalation. Cannabis should not be recommended for CH unless controlled trials with synthetic selective cannabinoids show a more convincing therapeutic benefit.
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.
Nabilone, a synthetic cannabinoid mimicking tetrahydrocannabinol (THC), has been shown to decrease analgesic intake while reducing MOH pain in a double-blind, placebo-controlled trial. 53 In this study, 26 patients with treatment refractory MOH completed a course of either nabilone (0.5 mg) or ibuprofen (400 mg) for 8 weeks, then after a week-long washout period, completed a second 8-week course of the previously excluded medication. Oral cannabinoid administration was chosen over an oromusocal THC spray, both because oral administration avoids the concentration peaks that can lead to euphoric effects and because chronic administration better overcomes individual differences in bioavailability. Although both substances showed improvement from baseline, nabilone was significantly more effective than ibuprofen in reducing pain intensity, analgesic intake, and medication dependence, as well as in improving quality of life. This study also examined the safety of nabilone as a treatment for headache and found that patients only experienced mild adverse effects that disappeared after discontinuation of the medication. The results of this study are significant, especially given that MOH is exacerbated by many pharmacological treatments. This study also highlights the potential value of cannabis in combination therapies, as a supplement to traditional treatments, or as a secondary treatment in refractory cases. Currently, a multicenter, double-blind, placebo-controlled study is being performed to examine the safety and efficacy of a dronabinol, or synthetic THC, metered dose inhaler for the treatment of migraine (clincaltrials.gov, NCT Identifier: <"type":"clinical-trial","attrs":<"text":"NCT00123201","term_id":"NCT00123201">> NCT00123201). When published, this study could give valuable insights into the efficacy and risks of cannabinoids for the treatment of migraines.
MS, multiple sclerosis.
The pathophysiology of headache disorders is still under investigation. However, it is believed that migraine and cluster headaches are initiated in the brain in areas such as the hypothalamus, brainstem, or possibly cortex. 6 Tension-type headaches can not only originate in the central nervous system but may also be triggered by myofascial tissue, often developing in response to stress. 10 Regardless of origin, headaches usually involve overactivation of the trigeminovascular pathway, resulting in the release of vasoactive peptides, such as calcitonin gene-related peptide (CGRP) and substance P, as well as vasoactive mediators such as nitrous oxide (NO), which can lead to further sensitization of nociceptive receptors in the head and neck. 11 Serotoninergic signaling, parasympathetic efferents, inflammation, and increased intracranial pressure also play important roles in headache disorders. 12,13
Case reports also give insights into the mechanisms behind the anti-headache action of cannabis. Smoking cannabis has been reported to relieve pain associated with pseudotumor cerebri, 57 a condition that is characterized by an increase in the intracranial pressure of an uncertain etiology. This suggests that the therapeutic effect of cannabis in some headache conditions could be a result of reducing intracranial pressure. In fact, dexanabinol, a synthetic cannabinoid, has been found to relieve intracranial pressure and improve outcomes after traumatic brain injury. 69
Historical Reports of the Use of Cannabis as a Treatment for Headache (19th and Early 20th Century)
Headache is a major public health concern, with enormous individual and societal costs (estimated at $14.4 billion annually) due to decreased quality of life and disability. 1 Each year, ∼47% of the population experience headache, including migraine (10%), tension-type headache (38%), and chronic daily headache (3%). 2 A sexual dimorphism exists for headache disorders, with women 2–3 times more likely to experience migraine 3 and 1.25 times more likely to experience tension-type headache than men. 4
Other studies have looked specifically at the change in the occurrence of headache disorders with use of cannabis. 52 One retrospective study described 121 patients who received cannabis for migraine treatment, among whom 85.1% of these patients reported a reduction in migraine frequency. 47 The mean number of migraines at the initial visit was 10.4, falling to 4.6 at follow-up visits after cannabis treatment. Moreover, 11.6% of the patients found that, when smoked, cannabis could effectively arrest the generation of a migraine. These results indicate that cannabis may be an effective treatment option for certain migraine sufferers.
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.
As for the pain, the THC-CBD combo appeared to reduce the severity of migraines by 43.5 percent and cluster headaches by 55 percent.
Just why it works isn’t yet clear, but it’s believed cannabinoids prevent the release of serotonin, which can narrow blood vessels. They may also have an anti-inflammatory effect.
The results are yet to be peer-reviewed.
Around 200mg seemed to be the sweet spot, with half that amount providing no benefits at all.