Patterns of medicinal cannabis use, strain analysis, and substitution effect among patients with migraine, headache, arthritis, and chronic pain in a medicinal cannabis cohort

Chronic pain was the most common reason for cannabis use, consistent with most registries.

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The majority of headache patients treating with cannabis were positive for migraine. Hybrid strains were preferred in ID Migraine™, headache, and most pain groups, with “OG Shark”, a high THC (Δ9-tetrahydrocannabinol)/THCA (tetrahydrocannabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes β-caryophyllene and β-myrcene, most preferred in the headache and ID Migraine™ groups. This could reflect the potent analgesic, anti-inflammatory, and anti-emetic properties of THC, with anti-inflammatory and analgesic properties of β-caryophyllene and β-myrcene. Opiates/opioids were most commonly substituted with cannabis. Prospective studies are needed, but results may provide early insight into optimizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and patterns of use in the treatment of headache, migraine, and chronic pain syndromes.

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The legal use of medicinal cannabis continues to increase globally, including the United States. At the time of this writing, there are currently 29 states which have legalized medicinal cannabis, 9 states and Washington DC which have legalized both medicinal and recreational cannabis use, and 18 states which have legalized cannabidiol (CBD)-only bills.

The use of medicinal cannabis for a multitude of health maladies, particularly chronic pain, has been well described through ancient, historical, and current times, and well supported through the medical literature [12345678910111213141516171819202122232425262728]. In 2017, The National Academies of Sciences, Engineering, and Medicine published a statement that the use of cannabis for the treatment of pain is supported by well-controlled clinical trials and that there is substantial evidence that cannabis is an effective treatment for chronic pain in adults [24]. In 2014, the Canadian Pain Society revised their consensus statement to recommend cannabinoids as a third-level therapy for chronic neuropathic pain given the evidence of cannabinoid efficacy in the treatment of pain with a combined number needed to treat (NNT) of 3.4 [25]. Most medicinal cannabis registries report that chronic pain is the most common indication for use [2930313233343536373839]. However, most of these registries do not further differentiate chronic pain into different pain subsets.

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Supporting evidence also exists for cannabis/cannabinoids in the treatment of migraine and/or chronic migraine [14041424344454647484950515253545556], cluster headache [56575859], chronic headaches [13446061], medication overuse headache [62], idiopathic intracranial hypertension [63], and multiple sclerosis associated trigeminal neuralgia [64]. Publications detailing this headache, migraine, and facial pain literature, as well as described mechanisms of pain relief with cannabis and cannabinoids are available and should be reviewed, but are beyond the scope of this paper [12285165]. At the time of this writing, the limited supporting headache literature consists of one retrospective analysis, numerous case series, case studies, and case reports, clinical/anecdotal reports, and surveys. There are no placebo-controlled studies of cannabis for headache disorders, although a multicenter, double-blind, placebo-controlled study evaluating efficacy and safety of a synthetic Δ9-tetrahydrocannabinol (THC), Dronabinol, in a metered dose inhaler for the treatment of migraine with and without aura has been completed, but results not available [66]. There are only two prospective trials containing a control group evaluating the use of cannabinoids in the treatment of headache disorders, specifically chronic migraine, cluster headache, and medication overuse headache [5662].

The first of these two prospective trials was a randomized, double-blind, active-controlled crossover trial with treatment refractory medication overuse headache (MOH) with daily analgesic intake for at least 5 years and several failed detoxification attempts. Patients completed a course of either Ibuprofen 400 mg or Nabilone 0.5 mg daily for 8 weeks, had a 1 week washout, then a second 8 weeks of the other medication. Results showed that Nabilone 0.5 mg daily, a synthetic cannabinoid, was superior in reducing daily analgesic intake, pain intensity, level of medication dependence, and improved quality of life in these patients [62].

The second prospective trial evaluated the use of cannabinoids as both a prophylaxis and acute treatment for both chronic migraine and chronic cluster headache [56]. Patients were given one of two compounds containing 19% THC or a combination of 0.4% THC + 9% CBD. In phase 1, dose finding observations to determine effective dosing was performed with a group of 48 chronic migraineurs. It was found that doses less than 100 mg produced no benefit, while an oral dose of 200 mg administered during a migraine attack decreased acute pain intensity by 55%, which was the dose used in phase 2. In phase 2, chronic migraine patients were assigned to 3 months prophylaxis treatment with either 25 mg per day of Amitriptyline or THC + CBD 200 mg per day. Chronic cluster headache patients were assigned to 1 month prophylaxis treatment with either Verapamil 480 mg per day or THC + CBD 200 mg per day. For acute pain attacks, additional dosing of THC + CBD 200 mg was allowed in both groups. In the migraine patients, the THC + CBD 200 mg prophylaxis provided a 40.4% improvement versus 40.1% with Amitriptyline. In the cluster headache patients, the THC + CBD 200 mg prophylaxis gave minimal to no benefit. Additional acute THC + CBD 200 mg dosing decreased pain intensity in migraine patients by 43.5%. This same result was seen in cluster headache patients, but only if they had a history of migraine in childhood. In cluster headache patients without a previous history of childhood migraine, the additional THC-CBD 200 mg abortive treatment provided no benefit as an acute treatment.

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It is unclear whether certain types of pain may respond better to certain cannabis strains with specific combinations of cannabinoids, terpenes, or other biochemical properties. There have been a multitude of studies showing benefit in many forms of chronic pain, but there have been no studies attempting to differentiate which types and strains of cannabis along with associated compositions of cannabinoids and terpenes may be more effective for certain subsets of pain. This information would be of great clinical use in providing direction for treatment recommendations by healthcare providers.

Original Article By: The Journal of Headache and Pain

Victor MadrilComment