Monday, November 23, 2020

Current evidence on use of cannabis for headache disorders

In a special workshop at the 2020 Virtual Scottsdale Headache Symposium, the evidence for potential benefits and harm of Cannabis use in people with headache disorders was presented. There are known anti-inflammatory and analgesic effects of compounds found in Cannabis. In particular, tetrahydrocannabinol (THC) reduces inflammation twice as much as hydrocortisone and 20 times as much as aspirin. Cannabidiol (CBD), which is not psychoactive, has anti-inflammatory effects that are orders of magnitude higher than aspirin. The terpenes have both anti-inflammatory and analgesic properties. It is postulated that the combination of these compounds in Cannabis creates synergistic effects. 

According to the National Academies of Science, Engineering, and Medicine, "use of Cannabis to treat pain is supported by well-controlled clinical trials with conclusive or substantial evidence that Cannabis is an effective treatment for chronic pain in adults." The number needed to treat with cannabinoids for pain benefit is approximately 3.4. 

In the nervous system, the cannabinoid 1 (CB1) receptor is dense in the central nervous system (CNS) and peripheral nervous system (PNS). In the brainstem, CB1 receptors inhibit trigeminovascular responses of the A-delta and C-fibers, both implicated in the pathophysiology of headache, and activation of the CB1 receptor is modulated by the 5-HT1B/D receptors, the same receptors acted upon by triptans. 

For headache disorders, however, the data are limited to case series, case reports, surveys, retrospective review, and only 2 prospective trials with a control group. A small controlled study of cannabinoids (oral compound of 200 mg 0.4% THC/9% CBD in a 200 mL fat emulsion) for treatment of chronic migraine (n=48) and determined no effect at doses under 100 mg, and a 55% decrease in pain intensity with doses of 200 mg. For preventive treatment, amitriptyline 25 mg/day vs 200 mg of the THC/CBD compound reduced migraine headache days over 3 months by 40.4% and 40.1% respectively. Additional acute dosing was allowed and in those with chronic migraine, this decreased pain intensity by 43.5%. 

A randomized double-blind active-control crossover trial to treat people with medication-overuse headache (daily analgesia for at least 5 years with 3 detoxification attempts that failed the patient; n=30). The artificial cannabinoid nabilone compared with ibuprofen (each given for 8 weeks with 1-week washout in between and order randomized) reduced daily analgesic intake, medication dependence, and pain intensity. 

A survey study of 2,032 individuals in Canada using medical Cannabis showed that 25% were treating headache as their primary symptom and 88% of these people had a positive diagnosis of migraine. Of these individuals, 55% had substituted Cannabis for another treatment, including opiates, antidepressants, nonsteroidal anti-inflammatory drugs (NSAIDs), antiseizure medications, and muscle relaxants. 

The importance of highlighting potential harms of Cannabis use with patients was also highlighted. Some of the features that point to misuse and abuse are using larger amounts than intended over a longer period than intended, cravings, wanting to stop but not being able to do so, and use in physically hazardous situations, such as while driving. It is important to note that approximately 1 in 10 Cannabis users develop substance abuse disorder. Side effects can also occur, including increased heart rate, changes to breathing rate, increased appetite, dry mouth, sleepiness, impaired cognition, and impaired coordination. Impaired driving ability is of particular importance.

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