The Cannabis Act was introduced to the Canadian House of Commons one year ago, which would legalize the possession and use of marijuana. The Act is expected to become law in July 2018. The medical use of marijuana was the thin edge of the legalization wedge, and the new law is likely to fuel even greater interest in marijuana among patients.
An examination of medical use is limited by the small number of studies of smoked marijuana. Most studies have examined a few of the many cannabinoids found in marijuana, notably tetrahydrocannabinol (THC), which is psychoactive, and cannabidiol (CBD), which is not. Synthetic formulations include oral dronabinol (THC; Marinol), and nabiximols (THC/CBD’ Sativex), which is an oral spray,
The following is a summary of the studies to date.
Epilepsy: A review of 6 randomized controlled trials and 30 observational studies concluded that oral CBD 20 mg/kg was more effective than placebo in reducing seizure frequency >50% (relative risk 1.74) and in achieving freedom from seizures (relative risk 6.17) (Stockings et al. J Neurol Neurosurg Psychiatry 2018; epublished March 6, 2018). Oral CBD may also be effective as adjuvant therapy in treatment-resistant pediatric epilepsy (Devinsky et al. Lancet Neurol 2016;15:270-278).
Parkinson’s disease: A small study (n=7) speculated that nabilone may reduce levodopa-induced dyskinesia (Sieradzan et al. Neurology 2001;57:2108-2111. A double-blind crossover study (n=19) subsequently found no evidence of a treatment effect on parkinsonian symptoms or levodopa-induced dyskinesia with oral cannabis extract (Carroll et al. Neurology 2004;63:1245-1250). A separate study on the neuroprotective effects of oral CBD found no clinical benefit, although patients reported improved quality of life (Chagas et al. J Psychopharmacol 2014;28:1088-1098).
Migraine: No randomized controlled trials have been performed to date. One retrospective chart review (n=121) in Colorado found that headache frequency among marijuana users decreased from 10.4 to 4.6 headaches per month. (Rhyne et al. Pharmacotherapy 2016;36:505-510). Overall, 39.7% reported positive effects. Smoked marijuana was most often used for acute migraine treatment, with 11.4% stating that it aborted their migraine.
The rationale for marijuana use in migraine are its effects on serotonin receptors (potentiation of 5-HT1A, inhibition of 5-HT2A) and modulation of glutamatergic neurotransmission (Russo EB. Neuro Endocrinol Lett 2004;25:31-39). THC has also been reported to reduce the unpleasantness, but not the intensity, of pain and hyperalgesia, in essence having a dissociative effect on pain perception by disrupting the functional connectivity between the amygdala and primary sensorimotor areas (Lee et al. Pain 2013;154:124-134). A potential role in chronic pain syndromes, such as fibromyalgia, has been suggested.
Huntington’s disease: A small placebo-controlled trial reported no significant improvement in motor, cognitive, hehavioural or functional outcomes with Sativex (Lopez-Sendon Moreno et al. J Neurol 2016;263:1390-1400. An early study found no benefit with Marinol (Consroe et al. Pharmacol Biochem Behav 1991;40:701-708).
Dementia: A small study of low-dose oral THC versus placebo found no significant improvement in neuropsychiatric symptoms (van den Elsen et al. Neurology 2015;84:2338). Treatment was well-tolerated and did not appear to adversely affect episodic memory.
Most studies of cannabinoids in neurology have involved patients with multiple sclerosis. These will be summarized in Part 2.