Cannabis and Headaches and Migraine

By Kimmi Stultz, PharmD, Chief Pharmacology Officer of Healthy Option Consulting, Inc.

The use of cannabis, or marijuana, for medicinal purposes is deeply rooted through history, dating back to ancient times. It is an herb used by humans for centuries and is the most commonly used drug in the world (United Nations Office on Drugs and Crime [UNODC], 2011). Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science. However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research. Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is supporting evidence.

Cannabindoid receptors are located widely throughout the brain (frontal lobe, somatosensory cortex, entorhinal cortex, and olfactory cortex) basal ganglia, hippocampus, amygdala, cerebellum, substantia nigra, and periaqueductal gray matter.   Descending modulation of trigeminovascular nociceptive transmission through midbrain nuclei is likely responsible for the quick anti-nociceptive effect on headache.[1]

Goadsby and colleagues demonstrated that the endogenous endocannabinoid anandamide (AEA) modulates pain signaling in the nervous system in various ways. AEA inhibits dural blood vessel dilation induced from neurogenic, calcitonin gene-related peptide (CGRP), electrical stimulation, capsaicin, and nitric oxide (NO) sources, and this effect is reversed by a cannabinoid antagonist.[2]Modulation of serotonergic pain transmission is well established in migraine treatment, particularly with the mechanism of action of the triptans. Endocannabinoids interact with serotonergic neurons in the brainstem dorsal raphe to modulate pain mechanisms. Cannabinoids have been shown to inhibit 5HT release from platelets during a migraine.[3] Endocannabinoids have anti-nociceptive effects by descending modulation of pain at the spinal level.[4] Endocannabinoid deficiency has been theorized as a possible cause for migraine and other chronic pain disorders, including chronic migraine and medication overuse headaches. Cannabinoids appear to modulate and interact at many pathways inherent to migraine, triptan mechanisms of action, and opiate pathways, suggesting a potential synergistic or related benefit.[5]

A study published from Skaggs School of Pharmacy and Pharmaceutical sciences at the University of Colorado looked at the effects of inhaled and ingested cannabis in migraine sufferers, and the results showed inhalation methods appeared to provide the fastest effects and were more likely to stop migraine headaches in their tracks. The next frontier in this field of research is figuring out which cannabinoids, strains, and delivery methods are most effective in treating headaches and migraines.[6] In the meantime, we’ll have to continue to relying primarily on anecdotal evidence.

If you are looking for safer, addiction-free, pain medication to address your migraines and other chronic pain, consider the use of medical marijuana.

[1] Akerman S. Holland PR, Goadsby Pj. Diencephalic and brainstem mechanisms in migraine. Nat Rev Neurosci. 2011; 12:570-584.

[2] Akerman S, Kaube H, Goadsby PJ. Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception. J Pharm Exp Therapeutics. 2004; 309:56-63

[3] Akerman S, Holland PR, Lasalandra MP, Goadsby PJ. Endocannabinoids in the brainstem modulate dural trigeminovascular nociceptive traffic via CB1 and “triptan” receptors: Implications in migraine. J Neurosci. 2013; 33:14869-14877

[4] Rossi C, Pini LA, Cupini ML, Calabresi P, Sarchielli P. Endocannabinoids in platelets of chronic migraine patients and medication-overuse headache patients: Relation with serotonin levels. Eur J Clin Pharmacol. 2008; 64:1-8

[5] Baron EP. Comprehensive Review of Medical Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache. Headache Currents. Vol 55, Issue 6, May 25,2015

[6] Rhyne DN, Anderson SL, Gedde M, Borgelt LM. Effects of Medical Marijuana on Migraine Headache Frequency in an Adult Population. Pharmacotherapy. 2016 May; 36(5): 505-10.

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