Cannabis Use Associated With Increased Medication Overuse Headache


Patients with chronic migraine were advised to reduce cannabis use to aid in reducing medication overuse headache.

Niushen Zhang, MD, department of neurology and neurological sciences, Stanford University School of Medicine

Niushen Zhang, MD

A recent electronic chart review found significant association between cannabis use and increased prevalence of medication overuse headache (MOH) in patients with chronic migraine (CM). Investigators further observed bidirectional cannabis-opioid association, both being significant associated with MOH—a condition that continues to create a high level of burden for patients with CM in the US.1,2  

Investigators conducted a chart review of patients seen between 2015 and 2019 at the Stanford Headache Clinic, with 368 charts meeting inclusion criteria (212 cases of CM with MOH and 156 referents with CM without MOH), namely adult patients with greater than 1 year of CM duration. The median age for cases was 42.8 years (interquartile range [IQR], 33.3-54.1), and the median age for referents was 40.1 years (IQR, 30.6-49.1; P = .009). Within cases, 122 patients (81%) were currently using cannabis and 90 were not; in referents, 28 patients (41%) were currently using cannabis and 128 were not, with an adjusted odds ratio of 6.3 (95% CI, 3.56-11.1; P <.0001). 

Cases accounted for 3 times as many patients reporting MOH when compared to referents (P <.0001), and cases were also using cannabis for longer stretches of time—approximately 4 times longer than referents, 19 months vs. 5 months, respectively. 

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“Using cannabis for the acute treatment of headache brings up the concern of whether cannabis can lead to the development of MOH just as some other migraine-abortive therapies have the potential of doing,” corresponding authors Niushen Zhang, MD, and Yohannes W. Woldeamanuel, MD, department of neurology and neurological sciences, Stanford University School of Medicine, wrote.1 

Cannabis use was also significantly associated with opioid use (Spearman’s rho [ρ] = 0.26; P <.0001), and cannabis use (ρ = 0.40; P <.0001) and opioid use (ρ = 0.36; P <.0001) were further associated with prevalence of MOH. Investigators found specific correlation between benzodiazepine use and cannabis (ρ = 0.16; P = .003), but no association between butalbital use and cannabis use (ρ = 0.02; P = .643). 

When conducting an agglomerative hierarchical clustering, 2 natural clusters were revealed. Within Cluster I (n = 188), patients reported 9.3 times more current use of cannabis (P <.0001) and 9.2 times more current use of opioids (P <.0001) when compared Cluster II (n = 180). Those in Cluster I also showed 1.8 times higher MOH burden (P <.0001). 

The study was limited since data was confined to a tertiary headache clinic and therefore may not be representative of the general CM population. There was also potential for bias due to the stigma surrounding cannabis use, which may render patients less likely to discuss their use. Investigators called attention to the need for further study, particularly by measuring THC-CBD components of different cannabis products, as results can be influenced by the proportion. 

“To the best of our knowledge, our results are the first to explore the relationship and MOH risks among these 4 dependence-causing drugs commonly used by patients with migraine, that is, cannabis, opioids, benzodiazepines, and butalbitals,” Zhang and Woldeamanuel said.1 “Of these 4 drugs, cannabis and opioid use significantly contributed to MOH prevalence in patients with CM even while adjusting for the other variables. It may be noteworthy to consider that cannabis-using patients with CM are at increased risk of opioid use, and the consumption of both cannabis and opioids increases the prevalence of MOH.”

Cannabis has also been a topic of discussion within the multiple sclerosis (MS) space, being used to treat associated symptoms such as pain, spasms, and anxiety. Surveys conducted in November of 2020 found that many health care professionals lacked knowledge of cannabis use, therefore inhibiting their ability to advise patients on suggested use and emphasizing the need to improve competence in this area.

1. Zhang N, Woldeamanuel YW. Medication overuse headache in patients with chronic migraine using cannabis: A case-referent study. Headache. Published online August 9, 2021. doi: 10.1111/head.14195
2. Schwedt TJ, Hentz JG, Sahai-Srivastava S, et al. Headache characteristics and burden from chronic migraine with medication overuse headache: Cross‐sectional observations from the Medication Overuse Treatment Strategy trial. Headache. 2021;61(2):351-362. doi:10.1111/head.14056
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