A comprehensive history and science review of medical cannabis, with a focus on headache and migraine | Research

The takeaway

Cannabis has deep historical roots in headache treatment, and cannabinoids interact with pathways relevant to migraine, but controlled clinical trials are almost entirely absent.

Read this if you have migraines or headaches and are curious whether cannabis has a scientific basis for relief.

100+ pharmacological compounds in cannabis, most poorly understood

What the researchers found

This extensive review traced the history of medicinal cannabis from ancient use through its prominence in 19th-century medicine, when it was widely prescribed for headache, to its prohibition driven by political rather than scientific factors. The author documented how cannabinoids interact with endocannabinoid, serotonergic, and opioid pathways relevant to migraine and other headache disorders.

The literature search found supportive but limited evidence for cannabis in several headache types, including migraine and cluster headache. Most evidence came from case reports, anecdotal accounts, and laboratory research rather than controlled trials.

The review identified over 100 pharmacological compounds in cannabis, noting that the majority remain poorly understood. The author argued that modulating the endocannabinoid system through various receptor targets could provide the foundation for new medication classes.

Why it matters

Migraine affects hundreds of millions of people globally, and existing treatments are often inadequate. If cannabinoid-based approaches could be validated through clinical trials, they could offer new options. But this review makes clear that the evidence base remains largely anecdotal.

The numbers in context

Almost half of US states had legalized medicinal cannabis at time of publication. Cannabis contains over 100 pharmacological compounds. The review covered headache, chronic pain, and multiple other state-approved conditions.

How the study worked

Comprehensive narrative review covering the history of medicinal cannabis, endocannabinoid system pharmacology, clinical evidence across state-approved conditions, and detailed analysis of headache and migraine literature. Sources were drawn from PsycINFO, MEDLINE, and Google Scholar.

What this study cannot tell us

Narrative review format means study selection was not systematic. Most headache-specific evidence was anecdotal or preclinical. The review was published when clinical trial activity was still limited by federal restrictions on cannabis research.

How to read the evidence

Extensive narrative review covering history, pharmacology, and clinical evidence, but limited by the absence of controlled trials for headache.

When this study was published

Published in 2015. Clinical trial activity for cannabis and headache has increased since.

The bigger picture

The story of cannabis in medicine is one of a treatment that was widely used, then banned for political reasons, and is now being reconsidered. For headache specifically, the historical record is surprisingly rich, but modern clinical trial evidence is remarkably thin.

Questions still open

Which specific cannabinoid compounds are most relevant to migraine pathways? Could low-dose cannabinoid formulations treat headache without psychoactive effects? Why has clinical trial evidence lagged so far behind the historical use and biological rationale?

Common questions

Can cannabis treat migraines?

There is historical and biological rationale suggesting it might help, but as of this 2015 review, controlled clinical trials were almost entirely absent. The evidence was mostly anecdotal and preclinical.

Why was cannabis removed from medical use?

According to this review, the shift from legal and frequently prescribed to illegal was driven primarily by political and social factors rather than scientific evidence of harm or inefficacy.

Read the original research

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been ….

Headache, 55(6), 885-916

View on PubMed ↗Publisher’s paper ↗

Citation

Baron, Eric P. (2015). Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It's Been ….. Headache, 55(6), 885-916. https://doi.org/10.1111/head.12570