CBD May Relieve the Pain of Migraines

Migraine is common, and one of the most disabling painful conditions. Migraines are initiated by a large variety of triggers that ultimately activate the trigeminal system of nerves that project to the cranial meninges and meningeal blood vessels residing on the brain's surface. The pain develops due to the subsequent release of calcitonin gene-related peptide (CGRP) and a family of proteins that induce inflammation in the outermost meninges. Frequent recurrence of migraine attacks alters the release of these pain-inducing molecules, ultimately sensitizing the trigeminal system and reducing the time between episodes, leading to chronic migraines.

The body’s own endocannabinoid system has many functions; one of these is the modulation of pain perception. It accomplishes this by reducing the release of CGRP and multiple proinflammatory proteins. Ingestion or inhalation of cannabis products also reduces the release of these molecules by activation of the type 1 cannabinoid receptor. This receptor responds to THC, the active ingredient in cannabis, and is also responsible for the psychoactive effects of cannabis. In contrast, cannabidiol (CBD) lacks any psychoactive effects. Indeed, it acts to inhibit the activation of the type 1 receptor and mitigate the actions of THC. CBD can suppress the release of inflammatory proteins that underlie migraine pain. The studies discussed below suggest that CBD might be able to reduce migraine pain.

Despite extensive historical use of cannabis in headache disorders, there is limited research on the effectiveness of CBD for migraine. Why should we expect that cannabinoids might be effective for migraines in humans? Clinical studies indicate that patients suffering with migraines, particularly women, have an endocannabinoid deficiency. Also, preclinical animal studies have provided evidence that supports the use of CBD in migraine models.

Promise Shown in Preclinical Animal Studies

A preclinical study using mice examined the ability of CBD on a model of migraine that involved a single administration of CGRP. A single CBD administration protected both females and males from pain induced by CGRP. CBD, injected after CGRP, reversed CGRP-evoked pain. The results demonstrate the efficacy of CBD in preventing episodic and chronic migraine-like states with reduced risk of causing medication-overuse headache. Most importantly, CBD also shows potential as an abortive agent for treating migraine attacks and headache-related conditions.

The analgesic effect of CBD is complex and still being investigated. CBD acts on a few different G protein-coupled receptors as well as some serotonin receptors. CBD also prevents the action of the pro-inflammatory enzymes cyclooxygenases and lipoxygenases. Finally, because of its similarity to THC, CBD may inhibit the inactivation of endogenous cannabinoids. Some of these endogenous cannabinoids have both analgesic and anti-inflammatory properties.

Another preclinical study using rats tested for the benefits of CBD using a well-known animal model of migraine based on systemic nitroglycerin (NTG) administration. After systemic administration, CBD was rapidly absorbed and distributed to the brain. CBD reduced NTG-induced trigeminal-related (facial) pain and significantly reduced the gene expression of CGRP and other pro-inflammatory proteins in migraine-relevant brain and body regions.

No Study Results on Humans Yet

No published studies focused on the clinical beneficial effects of CBD on migraine in human subjects have been published. A recent clinical trial reported that a mix of THC and CBD produced relief in chronic migraine and chronic cluster headache patients. However, the benefit could have been entirely related to the presence of THC. Two clinical trials are currently being conducted on the safety and efficacy of CBD alone. The results of these studies have not been published.

Overall, preclinical studies show a significant analgesic effect of CBD in animal models of migraines. Future positive studies in humans might lead to a novel additional treatment option for migraines.