By Ellen Feldman, MD

Altru Health System, Grand Forks, ND

Dr. Feldman reports no financial relationships relevant to this field of study.

SYNOPSIS: The authors of this observational study found nearly a 50% reduction in self-reported headache and migraine severity following use of inhaled medicinal cannabis.

SOURCE: Cuttler C, et al. Short- and long-term effects of cannabis on headache and migraine. J Pain 2019. pii: S1526-5900(19)30848-X. doi: https://doi.org/10.1016/j.jpain.2019.11.001. [Epub ahead of print].

Cannabis is legal for medicinal use in more than half of the 50 U.S. states.1 Multiple factors, including federal restrictions on funding cannabis research, have hindered the research necessary to provide evidence-based guidelines for use.2 Cuttler et al noted 35% of medical cannabis users cite headache or migraine as a primary reason for medicinal cannabis use, but studies regarding the specifics of the responses are limited to one randomized, double-blind study that included 30 outpatients. With barriers limiting a traditional research protocol, Cuttler et al used an innovative approach to gather data for this study. Strainprint is a free, Canadian-based app developed to collect analytics regarding medical marijuana. All data are anonymous. Users register with basic information (gender and birth date), select a symptom or medical problem and rate severity, enter the cannabis strain and method of administration, and then are prompted to re-rate severity of symptoms within 20 minutes to four hours after cannabis use. Severity ratings are based on a scale of 0 to 10. In this way, patients can track personal response to a specific strain of medical cannabis, while contributing information of use to researchers.3

Using Strainprint, Cuttler et al analyzed data from 1,306 medical cannabis users with headache (the app was used 12,293 times) and 653 medical cannabis users with migraines (the app was used 7,441 times). Eligibility criteria included using an inhaled form of medical cannabis, including smoking, vaping, and bubbler (edible and tincture users were excluded). The tetrahydrocannabinol (THC) and cannabidiol (CBD) content of the strain of cannabis also was documented; the app prepopulated this information for known strains sold by Canadian distributors. Overall symptom reduction in all subjects with headaches was 89.9%. App users rated headache symptoms on a scale of 0 to 10 before and up to four hours following inhalation of medicinal cannabis. The mean reduction in severity was 47.3%. A statistical analysis showed significant individual variation in the extent of headache reduction following medicinal cannabis use; response to similar doses and strains was highly variable. There appeared to be a correlation between severe initial ratings of headaches and greater severity reduction post-use. Repeated use of cannabis was correlated with less of an effect on symptoms (P = 0.010), suggesting tolerance to the cannabis. The concentrate was associated with greater reduction in headache severity (P < 0.001) and no indication of tolerance; however, limited sessions with concentrate were available. In app users with migraines, the overall symptom reduction was 88.1%.

App users rated migraine symptoms on a scale of 0 to 10 before and up to four hours following inhalation of medicinal cannabis. Mean migraine rating reports decreased by 49.6% following cannabis use. Similar to headaches, there was significant variation in the extent of pain severity reported post-inhalation. Different than headaches, there was no correlation between severe initial ratings and greater migraine severity reduction, and no significant difference in migraine relief was associated with the use of concentrate vs. flower. As with headaches, there was a significant increase in the dose of inhaled cannabis with repeated use (P = 0.0010), suggesting tolerance.

COMMENTARY

California introduced legalization of medicinal cannabis in 1996. Since then, 33 states have followed suit. There is an urgent need to complete studies, understand the risks and benefits of medicinal cannabis, and develop evidence-based clinical guidelines for the use of medicinal cannabis. The strength of this work is rooted in the innovative approach and plethora of data. Yet, to understand and attempt to apply the results clinically, consideration of the origin of the data (self-reports from the Strainprint app) is essential. Data were derived from 1,306 medicinal cannabis users with headache and 653 such users with migraine; both groups used the Strainprint app multiple times to rate response after cannabis use (12,223 times for the headache group and 7,441 times for the migraine group). However, it is noteworthy that there are no data regarding medicinal cannabis users who do not use Strainprint, and no information regarding the frequency of app use per individual, or if any of the respondents stopped using Strainprint after an initial attempt.

Medicinal cannabis users who tended to use the app most frequently may represent those individuals who were most satisfied with the results of using medicinal cannabis. If so, this would bias the results. In addition, the lack of a control group and lack of blinding weakens the ability to generalize and use the results with clinical confidence. Another feature of this study is that all subjects self-diagnosed and self-reported results. Thus, scales of pain severity were individualized, again leading to difficulty generalizing the results. Additionally, it would be useful to have external validation regarding the diagnosis of migraine and headache, as there do not appear to be any standard diagnostic criteria.

Cuttler et al found a slight but significant difference in gender response in the headache arm of the study, but not in the migraine arm. This is consistent with findings in a 2016 study, in which authors found inhaled cannabis to be a more powerful analgesic in men than in women. Future studies are necessary to determine any clinical significance to this finding.4 The headache results hint concentrate was more effective than flower in pain reduction. Cuttler et al noted the sample size of concentrate users was too small to draw conclusions (3.4% of subjects), but that this is an area ripe for exploration. Concentrate is a relatively newer form of cannabis with common names including “wax” and “dabs.” This concentrated form of cannabis contains higher-than-typical amounts of THC; there are case reports of concentrate use resulting in neurotoxicity, psychosis, and cardiotoxicity.5,6 Strainprint encourages documenting responses to medical cannabis, but does not collect detailed information on adverse effects. This must be taken into consideration to put the results of this analysis into context. Even with the clear limitations of this work, the results show marked promise for future investigation into the use of cannabis for headaches and migraines. There does appear to be an association of headache and migraine relief with the use of inhaled cannabis for some individuals. More research should help the medical field identify specific traits of the individuals and/or symptoms that best respond to this intervention.

For now, the primary care provider is on safe ground telling patients that although research is preliminary, this study points to the potential usefulness of medicinal cannabis in the treatment of headaches and/or migraine. The expectation of tolerance over time, as suggested by these results, should be included as part of an overall discussion. Cautionary notes include that there is not much information about side effects, effective dose, the effect of cannabis on any comorbid conditions, or cannabis interaction with pharmaceuticals or other substances. The hope is that with more robust and well-conducted studies, there will be better recommendations.

REFERENCES

  1. DISA. Map of marijuana legality by state. Updated April 2020.
  2. National Academies of Sciences, Engineering, and Medicine. Challenges and Barriers in Conducting Cannabis Research. In: The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research; 2017.
  3. Stainprint. Reports. 2020.
  4. Cooper ZD, Haney M. Sex dependent effects of cannabis-induced analgesia. Drug Alcohol Depen 2016;167:112-120.
  5. Cinnamon Bidwell L, et al. Exploring cannabis concentrates on the legal market: User profiles, product strength, and health-related outcomes. Addict Behav Rep 2018;8:102-106.
  6. Alzghari SK, et al. To dab or not to dab: Rising concerns regarding the toxicity of cannabis concentrates. Cureus 2017;9:e1676.