Potential therapeutic uses of cannabis
How cannabis may fit into your practice.
For over 5,000 years, the cannabis plant and its extracts were used for medicinal purposes.1 While much of the therapeutic value of cannabis has been derived from anecdotal reports, there is an increasing number of clinical studies demonstrating that medical cannabis and cannabinoids may be used to relieve the symptoms associated with various medical conditions.1
While cannabis has not been authorized for marketing in Canada for any particular purpose, some patients may benefit from medical cannabis use to alleviate a variety of symptoms.
Medical cannabis and pain
The endocannabinoid system is believed to have a role in endogenous pain control, with the elements of the endocannabinoid system found in central and peripheral pain pathways.1,2 Therefore, targeting this system with medical cannabis may be advantageous for pain therapy.2
While preclinical studies suggested that cannabis may relieve both acute and chronic pain, studies in experimental models of pain in healthy volunteers and in those from clinical trials suggested that cannabinoids may be more effective for the alleviation of chronic than acute pain.1,2 Chronic pain, unlike acute pain, is considered to be a much more complex condition composed of physical, psychological, and psychosocial factors, which contribute to a reduced quality of life.
Neuropathic pain or chronic non-cancer pain
In 2015, the Canadian Pain Society updated their guidelines for the management of neuropathic pain moving cannabis from the fourth- to a third-line medication.3 The strongest evidence for cannabinoid use is for neuropathic pain from HIV, diabetic neuropathy, posttraumatic or postsurgical neuropathic pain and peripheral neuropathic pain states.4 Clinical studies review presented in the 2013 Health Canada document also indicated that the addition of cannabinoid medications to conventional therapy was moderately effective for the treatment of neuropathic pain.1,2 Since 2013, ten more studies on cannabinoids in neuropathic pain were published.2 Among them, six blinded, randomized-controlled trials and two open-label trials unanimously demonstrated statistical significance in at least one or more measurements of neuropathic pain, including some responders with 30% reduction in pain using visual analogue and numeric scales (reviewed in Mohamed et al., 2018).2 Despite the strong evidence for use of cannabinoids in chronic neuropathic pain, there are still gaps in the knowledge that need to be addressed, such as the role of terpenoids, other cannabinoids and most beneficial modes of administration.2
“Opioid-sparing effect” is the ability of the non-opioid medication to provide an analgesic effect in conjunction with the lower dose of an opioid, thus decreasing opioid-associated side effects.1 Various pre-clinical studies suggested the existence of functional interaction between cannabinoid and opioid system and reported additive and even synergistic analgesic effects when using the combination of different opioids (morphine, codeine) and THC. In contrast, clinical results are mixed, and therefore this topic requires further investigation.1
Pain associated with arthritis and musculoskeletal disorders
Arthritis, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout and many other musculoskeletal disorders that target or involve the joints are characterized by significant pain.1 Scientific studies have demonstrated that joints, bone, and muscle all contain a working endocannabinoid system that potentially can be a target for cannabinoids.
Despite that there is relatively little scientific or medical information on the use of cannabis or cannabinoids to treat either arthritis or musculoskeletal disorders, the current regulations allow the use of dried cannabis for those patients experiencing pain due to these conditions, who have either not benefited from, or would not be considered to benefit from conventional treatments.1
Medical cannabis and anxiety
The endocannabinoid system has been shown to play an important role in modulating anxiety and depression.1 Suppression of endocannabinoid signaling is linked to induction of depression-like behaviour in humans, while stimulation of CB1 receptors was shown to reduce anxiety-like behaviour and increase antidepressant -like responses in animals.1 These findings indicate that proper endocannabinoid tone plays an important role in regulating mood.1
A survey of long-term cannabis users reported reductions in anxiety, increased relaxation, and relief from tension; however, clinical evidence that cannabinoids are an effective treatment for anxiety symptoms is limited.1 According to the recommendations of the College of Family Physicians of Canada, dried cannabis should be authorized with caution in those patients who have a concurrent active mood or anxiety disorder.5
Medical cannabis and sleep disturbances
Evidence suggests a role for the endocannabinoid system in sleep.1 Use of cannabinoids have been linked to a decreased sleep latency with greater ease in getting to sleep, but consistently reduced total rapid-eye movement (REM) sleep and REM density.1
Potential beneficial role for medical cannabis was shown in the studies of sleep difficulties or disturbances associated with chronic pain (cancer pain, chronic non-cancer pain, diabetic peripheral neuropathy), HIV-associated anorexia-cachexia, multiple sclerosis, amyotrophic lateral sclerosis, spinal cord injury, rheumatoid arthritis, fibromyalgia, inflammatory bowel disease, multiple sclerosis-associated bladder dysfunction, post-traumatic stress disorder, and chemosensory alterations and anorexia-cachexia associated with advanced cancer.1
Medical cannabis and energy imbalance
There is scientific evidence that the endocannabinoid system plays an important role not only in modulating appetite, food palatability, and intake, but also in regulating energy homeostasis (e.g., lipid and glucose metabolism).1 The regulation of energy balance by the endocannabinoid system appears to occur in the CNS and in multiple peripheral organs (white adipose tissue, skeletal muscle, pancreas, liver, and small intestine).1
Since CB1 receptors are expressed in mitochondria, while CB2 receptors are expressed in adipose tissue and liver, dysregulation of the endocannabinoid system is associated with the development of metabolic syndrome, obesity, and potentially, an increased risk of atherosclerosis and type-2 diabetes.1,6 In general, overactivity of the endocannabinoid system is associated with increased nutrient intake, enhanced energy storage, and reduced energy expenditure.1 Consequently, influencing the endocannabinoid system activity with cannabinoids may be t beneficial in patients that are in need of regulating their energy homeostasis.
Medical cannabis and adverse effects.
The majority of the information available up to date on the adverse events of cannabis is based on the studies of recreational use of cannabis, and not on studies of cannabis for therapeutic purposes.1 In the Canadian systematic review of the adverse effects of prescription cannabinoid medications, the most frequently cited adverse events were nervous system disorders, psychiatric disorders, gastrointestinal disorders, and vascular and cardiac disorders.1
The 2018 clinical practice guidelines for prescribing medical cannabinoids in primary care indicated that in multiple research trials harms of cannabinoids were consistent and common across all prescribing considerations.7 The approximate risk of adverse events was reported to be 80% versus 60%, and the risk of withdrawal due to adverse events was 11% versus 3%, for cannabinoids and placebo, respectively (See Table 1 for more details).7
Table 1: Adverse events and estimated event rates for medical cannabinoids, with GRADE of evidence rated high (Adapted from Allan GM et al., 2018)7
|Type of adverse event||Cannabinoid event rate, %||Placebo event rate, %||NNH|
|Withdrawal due to adverse events||11||Approximately 3%||14|
|Serious adverse events||NS||NS||NS|
|Central nervous system effects||60||27||4|
|Ataxia or muscle twitching||30||11||6|
|Disturbance in attention or disconnected thoughts||17||2||7|
|Disorientation of confusion||9||2||15|
|Blurred vision or visual hallucination||6||0||17|
|Dissociation or acute psychosis||5||0||20|
- GRADE—Grading of Recommendations Assessment, Development and Evaluation; NNH—number needed to harm; NS—not statistically significant.
- Examples of harms were selected from the largest statistically significant meta-analyses providing event rates.
- *Confidence intervals suggest that harm is likely (risk ratio = 3.41, 95% CI 0.95-12.27), so estimated NNH provided.
Special considerations for authorizing dried medical cannabis
Medical cannabis is not appropriate for patients who:5,8
- Are under the age of 25
- Have a personal or family history of serious mental disorders such as schizophrenia, psychosis, depression, or bipolar disorder
- Have a current or past cannabis use disorder, or an active substance use disorder (a history of alcohol or drug abuse or substance dependence)
- Are allergic to any cannabinoid or to smoke have cardiovascular, respiratory, renal or liver disease
- Are pregnant, are planning to get pregnant, or are breast-feeding
- Are a man who wishes to start a family
1. Health Canada. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids. 2013. https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids.html. Accessed August 28, 2018.
2. Mouhamed Y, Vishnyakov A, Qorri B, Sambi M, Frank SS, Nowierski C, et al. Therapeutic potential of medicinal marijuana: an educational primer for health care professionals. Drug Healthc Patient Saf. 2018;10:45-66. doi: 10.2147/DHPS.S158592. eCollection 2018.
3. Moulin DE, Boulanger A, Clark AJ, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19(6):328–335.
4. Mu A, Weinberg E, Moulin DE, Clarke H. Pharmacologic management of chronic neuropathic pain. Can Fam Physician. 2017;63(11):844-852.
5. The College of Family Physicians of Canada. Authorizing Dried Cannabis for Chronic Pain or Anxiety. Preliminary guidance. September 2014. https://www.cfpc.ca/dried_cannabis_prelim_guidance/. Accessed September 28, 2018.
6. Zou S, Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018;19(3): 833-856.
7. Allan GM, Ramji J, Perry D, Ton J, Beahm NP, Crisp N, et al. Simplified guideline for prescribing medical cannabinoids in primary care. Can Fam Physician. 2018;64(2):111-120.
8. Health Canada. Consumer Information – Cannabis (Marihuana, marijuana). July 2016. https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/licensed-producers/consumer-information-cannabis.html. Accessed September 28, 2018.