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

DOI: https://doi.org/10.1186/s10194- 018- 0862- 2

Abstract-Summary It would be clinically useful to identify patterns of cannabis treatment in migraine and headache, as compared to arthritis and chronic pain, and to analyze preferred cannabis strains, biochemical profiles, and prescription medication substitutions with cannabis.

Via electronic survey in medicinal cannabis patients with headache, arthritis, and chronic pain, demographics and patterns of cannabis use including methods, fre- quency, quantity, preferred strains, cannabinoid and terpene profiles, and prescrip- tion substitutions were recorded.

Cannabis use for migraine among headache patients was assessed via the ID Migraine™ questionnaire, a validated screen used to predict the probability of migraine.

Across all 21 illnesses, headache was a symptom treated with cannabis in 24.9%

(n = 505).

88% (n = 445) of headache patients were treating probable migraine with

cannabis.

Many pain patients substituted prescription medications with cannabis

(41.2–59.5%), most commonly opiates/opioids (40.5–72.8%).

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

most registries.

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 (tetrahydrocan- nabinolic acid), low CBD (cannabidiol)/CBDA (cannabidiolic acid), strain with predominant terpenes β-caryophyllene and β-myrcene, most preferred in the head- ache and ID Migraine™ groups.

Prospective studies are needed, but results may provide early insight into opti- mizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and pat- terns of use in the treatment of headache, migraine, and chronic pain syndromes.

Extended: Chronic pain was the most frequently reported primary illness for which medicinal cannabis was being used at 29.4% (n = 598), arthritis was 9.3% (n = 188), and headache was 3.7% (n = 75).

Chronic pain was the most common primary illness in which headache was reported to be a primary symptom being treated with medicinal cannabis (29.3%), followed by mental health condition (25.9%) and headache (14.9%).

The majority of this data comes from preclinical studies involving animal mod- els or in  vitro studies, and some of the reported benefits attributed to individual

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terpenes come from studies evaluating whole essential oils or plants in which the specified terpene may be a predominant constituent.

The majority of patients across all pain groups including the positive ID Migraine™, headache as primary symptom, chronic pain, and arthritis groups all preferred Hybrid cannabis strains followed by Indica, Sativa, and higher CBD strains (1:1 CBD:THC, 3:1 CBD:THC) when patients with headache as primary symptom were included.

The majority of patients treating headache with medicinal cannabis were positive

for migraine (88%) according to the ID Migraine™ questionnaire.

Background 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 [568, 569].

The second prospective trial evaluated the use of cannabinoids as both a prophy- laxis and acute treatment for both chronic migraine and chronic cluster head- ache [568].

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 treat-

ment with either Verapamil 480 mg per day or THC + CBD 200 mg per day.

Additional acute THC + CBD 200 mg dosing decreased pain intensity in migraine

patients by 43.5%.

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.

Methods A French and English electronic survey was sent to 16,675 Tilray medicinal can- nabis patients.

A $10 account credit was offered to each patient completing the online survey,

funded by Tilray.

If the patient answers “Yes” to 3 of these questions, there is a 97% chance they

have migraine.

Patients were asked a multitude of additional questions involving demographics, primary illnesses and symptoms treated with cannabis, frequency and quantity of use, favorite cannabis types and strains, methods of use, and prescription drugs substituted with cannabis.

Patients who reported headache as the primary illness were compared with each

patient group reporting a diagnosis other than headache as the primary illness.

Pearson chi-squared tests, or Fisher’s exact tests where appropriate, were used to compare headache patients with each non-headache patient group, with regards to five cannabis strains: Hybrid, Indica, Sativa, 3:1 CBD:THC, and 1:1 CBD:THC.

3.5 Medication Overuse and Addiction

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Results Preferred cannabis types and strains were first analyzed between the headache as primary symptom, headache as primary illness, chronic pain as primary illness, and arthritis as primary illness groups.

Indica strains were preferred in the insomnia/sleep disorders group, Sativa strains in the mental health condition/PTSD group, and Hybrid strains in the gastrointesti- nal disorder/Crohn’s Disease group, regardless of whether patients with headache as a primary symptom were included or not.

Patients with headache as primary symptom were 2.7 times as likely to prefer Sativa over 1:1 CBD:THC (OR 2.66, 95% CI 1.52-4.66, p < .001) when compared to chronic pain patients.

Many patients across all groups had replaced prescription medications with

medicinal cannabis, including headache as primary symptom n = 272 (53.9%).

The most common prescription medications replaced by medicinal cannabis were opiates/opioids in every pain group, including headache as primary symptom n = 118 (43.4%).

Discussion Given the entourage effects of cannabis [570, 571], where cannabinoids and ter- penes influence activity of one another, resulting in strain-specific characteristics, effects and responses, it is often unclear if these studies showing positive (or nega- tive) effects of cannabis are due to the THC alone, or due to synergy between unde- fined compositions of other cannabinoids and terpenes.

Other cannabis extract studies of only THC and CBD in varying doses also showed pain benefit, although these did not evaluate each cannabinoid individually [572, 573].

Most strains utilized today are Hybrids designed with standardized ratios of CBD, THC, other cannabinoids, and other compounds such as terpenes and flavo- noids, targeting specific symptoms, responses, and end user effects.

The majority of patients across all pain groups including the positive ID Migraine™, headache as primary symptom, chronic pain, and arthritis groups all preferred Hybrid cannabis strains followed by Indica, Sativa, and higher CBD strains (1:1 CBD:THC, 3:1 CBD:THC) when patients with headache as primary symptom were included.

Conclusions Identifying differences in use patterns between migraine, headache, arthritis, and chronic pain syndromes may be helpful in optimizing crossbred cannabis strains, synergistic biochemical profiles, or dosing differences between these pain subsets.

The majority of patients treating headache with medicinal cannabis were positive

for migraine (88%) according to the ID Migraine™ questionnaire.

This suggests that most headaches being treated with medicinal cannabis were

likely of migrainous pathophysiology.

Vaporizing or joint use were the primary methods of use across all groups, including migraine and headache, likely reflecting the need for a quick acting

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inhaled or non-orally ingested therapy in migraine attacks before severe pain and nausea/vomiting become prominent.

These results may provide early insight and a framework for direction into opti- mizing crossbred cannabis strains, synergistic biochemical profiles, dosing, and pat- terns of use that may be of clinical benefit in the treatment of headache and migraine, as well as other chronic pain syndromes.

Acknowledgement A machine generated summary based on the work of Baron, Eric P.; Lucas, Philippe; Eades, Joshua; Hogue, Olivia. 2018 in The Journal of Headache and Pain.

Alteration of gray matter texture features over the whole brain in medication- overuse headache using a 3-dimentional texture analysis