“Since the ’90s I’ve been on constant high doses of carbamazepine and gabapentin. The periodic pain breakthroughs were only controlled by hydrocodone, which always made me feel. uncomfortable,” wrote Glen, a participant in Axon’s informal study. “What a change CBD oil has made: no more carbamazepine or hydrocodone, and only half the gabapentin—and far better pain control. Pain breakthroughs still happen, but another squirt of Axon CBD, and the pain is gone within 15 minutes. I have no side effects.”
Photo courtesy of Axon Relief
As many as 39 million Americans experience migraine.
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Participants completed the Hit-6 survey both before and after using the CBD oil. During the 30-day trial period, respondents experienced an average of 3.8 fewer headache days than before using Axon’s CBD oil, a reduction of 23%. Chronic migraine sufferers, defined as people who experience 15 to 29 headache days over a 30-day period, saw a 33% reduction in their headache days.
Another participant in the study said that the CBD formulation “has significantly helped with my chronic migraines. If taken at onset, I can rely on it to take the edge off relatively quickly.”
One Billion Migraine Sufferers Worldwide
Although some research has shown that migraine sufferers report more relief from cannabis than they do from prescription medications, clinical studies that focus specifically on the effect that CBD can have on migraine are yet to be conducted. However, a 2018 study found that CBD, a non-intoxicating constituent of cannabis, has several pharmacological properties including acting as an anti-inflammatory, and anecdotal accounts of CBD oil successfully being used for migraine show promise.
The Axon CBD oil used in the migraine study.
While medical cannabis exists in different forms, there is variability in the ideal dosage for medical cannabis use. Several studies done to determine the “ideal” dosage are described here. Ogborne et al., in 2000, interviewed 50 medical cannabis users recruited via advertisements in newspapers and job boards . The participants were using medical cannabis for various reasons such as HIV, cramps, depression, pain, and migraines . Almost all of the participants smoked cannabis approximately two to three times a day . Baron et al., in 2018, in their electronic survey for the use of medical cannabis in a patient with headache, showed a pattern of cannabis use, including frequency, quantity, and strains . In the ID Migraine™ questionnaire, hybrid strains of cannabis, of which “OG Shark,” a high THC/THCA, low CBD/CBDA, and strains with predominant terpenes β-caryophyllene and β-myrcene, were most preferred in the headache and migraine groups . In the study trial, patients were intervened with 19% THC or THC+ 9% CBD . It was found that a dose of 200 mg effectively reduced the intensity of migraine pain by 55% . In another phase, 25 mg of amitriptyline or THC+CBD 200 mg per day was given prophylactically for three months in chronic migraine patients ; also, THC + CBD 200 mg was required for the acute attack . The study concluded that THC + CBD 200 mg had a 40.4% improvement over amitriptyline use (40.1%) . A similar study was done for the cluster headache, but it did not benefit as abortive treatment . Sexton et al., in 2016, did an online survey that sought to collect epidemiological data to start a discussion on medico-legal recommendations, report patient outcomes, and inform the medical practice of medical cannabis users . Many medical professionals (59.8%) used cannabis as an alternative treatment for their patients, reducing the symptoms by 86% . This study also included the route and dosage of medical marijuana usage, where 84.1% of the participants had inhalation as the most common route, and 60.8% of the participants reported one to five hits usage per session . Concerning the dosage of cannabis, 12.3% of respondents used less than 1 g/week, 20.3% reported using 1-2 g/week, 31.8% reported using 3-5 g/week, 26.1% reported using 7 g/week, 6% using 28 g/week, and 3.4% using more than 28 g/week . The survey was limited due to self-reported results, placebo effects, recall bias, and how efficacy was reported . In this situation, the amount utilized per week ranges from 1 to 28 g [26,32]. Frequency is also a concern, as patients vary from “1-10 hits per day” or 2-3 times per day depending on the convention used [26,32].
Cannabis ideal dose and preferred forms
The review article shows encouraging data on medicinal cannabis’s therapeutic effects on alleviating migraines in all of the studies reviewed. Beneficial long-term and short-term effects of medicinal cannabis were reported. It was effective in decreasing daily analgesic intake, dependence, and level of pain intensity. Some patients experienced a prolonged and persistent improvement in their health and well-being (both physically and mentally) after long-term use of medicinal cannabis. Overall, patients reported more positive effects rather than adverse effects with medical cannabis use. Chronic pain and mental health are the two reasons where medical cannabis is used often. It is found that some medical providers are hesitant to recommend medical cannabis due to a lack of current evidence, medical professional training, and a lack of uniform medical cannabis use guidelines. The therapeutic benefits of cannabis should be studied widely with intensive research trials supervised and controlled by authorities for safety and quality effectiveness. Further research should be performed once cannabis becomes legalized to determine a favorable delivery method, dose, and strain for migraine and chronic headache management and possible long-term effects of medical cannabis use. While medical cannabis is in a “disorganized realm” at the moment due to a lack of substantial research and medical provider education and patient education, this field is evolving and expanding to provide up-to-date research for both patient and doctor.
Cannabis has been long used since ancient times for both medical and recreational use. Past research has shown that cannabis can be indicated for symptom management disorders, including cancer, chronic pain, headaches, migraines, and psychological disorders (anxiety, depression, and post-traumatic stress disorder). Active ingredients in cannabis that modulate patients’ perceptions of their conditions include Δ 9 ‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. These compounds work to produce effects within the endocannabinoid system to decrease nociception and decrease symptom frequency. Research within the United States of America is limited to date due to cannabis being classified as a schedule one drug per the Drug Enforcement Agency. Few anecdotal studies have found a limited relationship between cannabis use and migraine frequency. The purpose of the review article is to document the validity of how medical cannabis can be utilized as an alternative therapy for migraine management. Thirty-four relevant articles were selected after a thorough screening process using PubMed and Google Scholar databases. The following keywords were used: “Cannabis,” “Medical Marijuana,” “Headache,” “Cannabis and Migraine,” “Cannabis and Headache.” This literature study demonstrates that medical cannabis use decreases migraine duration and frequency and headaches of unknown origin. Patients suffering from migraines and related conditions may benefit from medical cannabis therapy due to its convenience and efficacy.
Several studies have reported preferred forms of medical cannabis for the treatment of migraines and headaches. Salazar et al. conducted a cross-sectional survey to assess self-reported reasons for recreational and medical cannabis users in the southeastern United States . From the survey, 50 participants (11.6%) reported medical cannabis use, 180 participants (41.7%) reported recreational use, and 202 participants (46.8%) reported combined usage . The reported primary method of use was smoking, followed by vaporization (5.6%) and “dabs” (2.8%) . Participants were asked about their cannabis use, frequency, amount, and methods to use it . The survey’s results showed that 35.5% of the patients used it for headaches and migraines . The effect of medicinal cannabis on headaches and other conditions had a mean score of 3.6/5, which meant an 86% efficacy in pain relief . The dried Cannabis flower may be an effective medication for the treatment of migraine- and headache-related pain, but the effectiveness differs according to characteristics of the Cannabis plant, the combustion methods, and the age and gender of the patient . Many patients were able to replace their pain meds with medicinal cannabis in a survey reported by Nicolodi et al. . Limitations of this study include relying upon self-reported data along with a lack of diagnosis verification . Boehnke et al., in 2019, conducted an online survey consisting of 1321 patients on medicinal cannabis use . This survey analyzes cannabis use patterns among chronic pain patients . More females, 59.1%, participated in the survey in comparison to male patients . Males use smoke and vaporize form more, whereas females rank edible, tincture (oil-based), and topical cannabis as preferred first-line methods and also products that consist of low THC to high CBD in a “ratio” . Piper et al., in 2017, conducted an online survey to evaluate the effects of medical cannabis usage by substituting opioids or other psychoactive medications and evaluated the communication about the usage of the patients with their physician . This survey included 52.9% female and 47.1% male patients . The results show that 76.7% reported a gradual decrease in opiate use . Approximately, two-thirds of patients reduced anti-anxiety, migraine medications, antidepressants, and alcohol following MC usage . Preferred delivery methods include joints (48.5%), vaporization (22.3%), edibles (14.3%), tinctures (10.8%), concentrates (3.4%), and topical (0.7%) methods . This survey is limited as it did not examine “combination” medication use (antidepressant + sleep aid), and the data were designed to be interpretable by the general population . Rhyne et al., in 2016, conducted a retrospective, observational review of patients in Colorado . Patients between the ages of 18 and 89 years old with a diagnosis of migraines were included in the study . Factors such as sex, the duration of migraines, medical history, past migraine treatment, number of migraines experienced per month, how often and how much cannabis was used were self-reported by the patient . It was reported that out of 82, 20 patients used at least two forms of cannabis . The study has shown different forms of cannabis used to treat migraines .
Cannabinoids, similar to other analgesics and recreational drugs, act on the brain’s reward system, especially on cannabinoid one receptor localized at the same place as opioid receptors on nucleus accumbens and functions by overlapping the antinociceptive pathways . Articles included in our study focused on identifying the cannabis treatment in migraines and headaches. These articles also analyzed the preferred cannabis forms and their substitution for medications. During the extensive search of the literature, we came across three main questions for which the studies are conducted and directed: (i) Is medical cannabis effective on headaches and migraines? (ii) What forms of medical cannabis do people prefer? (iii) What is an ideal dose for the “preferred form?”
Despite mixed findings regarding the effectiveness of medical cannabis on both headaches and migraines, there is a consensus for the indication of medical marijuana therapy when first and second-line treatment fails. Current ethnobotanical and anecdotal references mention efficacy. Biochemical studies of THC and anandamide have provided a scientific basis for both symptomatic and prophylactic treatment of migraine . Dronabinol and nabilone, synthetic cannabinoids, have been shown to act in place of first-line therapy for cluster headaches (triptans, verapamil) and can effectively control pain [16,26]. Non-synthetic cannabis (oral, inhaled, sublingual, edible, topical) can be indicated for managing headache and migraine symptoms, but it is dose-dependent [22,23]. Adverse reactions to medical cannabis use can include dizziness, dry mouth or eyes, nausea, vomiting, and psychosis . Despite such side effects, patients have an overall favorable view of using medical cannabis along with or in place of medications, as it was reported to decrease the frequency and duration of migraines.
This paper aims to determine if medical cannabis can be utilized as an alternative treatment for headache and migraine management. It emphasizes how medical cannabis can reduce headaches and migraine duration and frequency, highlights different forms and ideal doses used for clinical effectiveness. After an extensive literature search using PubMed and Google scholar databases, 34 relevant articles were found to review the efficacy of medical marijuana use on migraines and headaches. Keywords used were “Cannabis,” “Medical Marijuana,” “headache,” “Cannabis and Migraine,” “Cannabis and Headache.” The articles were thoroughly screened by reviewing each article with titles, abstracts, and content of the full articles. We included the studies published between 1987 and 2020, human studies in the English language, including adults 18 years and older, whereas articles involving children less than 17 years and pregnant females were excluded from this study.
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.
Many individuals are currently using cannabis for the treatment of migraine and headache with positive results. In a survey of nine California clinics (N=1746), physicians recorded headaches and migraines as a reason for approving a medical marijuana ID card in 2.7% of cases, and 40.7% patients self-reported that cannabis had therapeutic benefits for headaches and migraines. In another California survey of 7525 patients, 8.43% of patients reported that they were using medical cannabis to treat migraines. Another survey of 1430 patients found that 9% of patients were using medical cannabis to treat migraines (subdivided into 7.5% for classical migraines, 1% for cluster headaches, and 0.5% for others). Other studies have reported the use of cannabis for migraine or headache relief, with specific estimates including 5% (N=24,800) and 6.6% (N=128) for migraines and 3.6% (N=128) and 7.4% (N=217) for headache.
Historical Reports of the Use of Cannabis as a Treatment for Headache (19th and Early 20th Century)
The schedule 1 classification of marijuana in 1970 has made rigorous clinical studies on the treatment efficacy of this substance difficult. Currently, there are no placebo-controlled clinical studies examining the use of cannabis for headache; nevertheless, there have been a number of other studies published that give insight into its therapeutic efficacy ( Table 2 ). 19,43–58 However, care should be taken when interpreting the findings from these studies. With one exception, 53 these studies did not include a control group, and given that the placebo effect can be altered by the context of treatment, 59 it is reasonable to expect a significant placebo response given the pre-existing public popularity and notoriety of cannabis. Moreover, self-reports and case studies may have a bias toward immediate improvement without awareness of possible dependence, rebound, or withdrawal responses, which are important concerns in headache treatment. 60 In fact, studies show that headache can be induced in 23.2% patients undergoing cannabis withdrawal. 61
Clinical Reports of the Use of Cannabis or Exogenous Cannabinoids as a Treatment for Headache
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.
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.
Clinical Studies on Cannabis Use for Headache
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.
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