Introduction: medical cannabis and pain

The cannabis plant, also known as hemp or marijuana, is one of the oldest documented medicines in history. Various strains of cannabis exist, but there is no consensus on whether Sativa, Indica, and Ruderalis are three separate species or subspecies of Cannabis sativa. Cannabis contains 545 chemical compounds, 104 of which are cannabinoids, the rest being flavonoids, terpenes, fatty acids, among others - all with potential medical uses.1 The best-characterized constituent is Δ9-tetrahydrocannabinol (THC), the principal psychoactive component of cannabis. Other important constituents include cannabidiol (CBD) and cannabinol. The former lacks psychoactive capabilities, whereas the latter is a mildly psychoactive chemical.1,2 Cannabinoids produce their effects through the activation of two distinct G-protein-coupled receptors termed cannabinoid CB1 and CB2. The CB1 receptor is expressed at high levels in the central nervous system (CNS) and along pain pathways. In contrast, the CB2 receptor is found predominantly, although not exclusively, outside the CNS, where it is most densely expressed in peripheral tissues with immune functions. The isolation of endogenous ligands (endocannabinoids, mainly anandamide and 2-arachidonoylglycerol) suggests that cannabinoids may play an important role in mediating a variety of neurophysiological processes including nociception.

Figure
figure 1

Algorithm for treatment with medical cannabis (adapted with permission from the Canadian Pain Society’s guidelines for the use of cannabinoid compounds in chronic pain).55

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These major pharmacological discoveries of the 1990s sparked interest in the possible medical uses for cannabinoids as potential analgesics. To date, 26 randomized clinical trials (and also some follow-up studies) are looking at the efficacy of various cannabinoids for treating various chronic pain conditions.3-5 In this paper, we present the new Canadian regulations on medical cannabis and the current provincial licensing authorities regulations in Canada, identify marijuana available on the Canadian market (companies, plants and drugs, mode of deliveries), give an update on clinical studies published during the last five years on cannabis and pain, and finally provide guidance on the use of medical cannabis in 2016 in Canada.

New Canadian regulation on medical cannabis

In 2001, the Canadian government enacted regulations for access to dried marijuana for medical purposes through the Marihuana Medical Access Regulations (MMAR).6 It came about after a decision by the Ontario Court of Appeal that allowed Terrance Parker, an epileptic patient, to use marijuana to treat his severe epilepsy.7 Under MMAR, patients were allowed to submit applications to Health Canada to obtain authorization to possess marijuana. These applications required validation by one or two physicians that the patient was suffering from medical conditions for which medical marijuana use was approved. Authorized patients were able to purchase marijuana from Health Canada, grow their own marijuana, or obtain marijuana from a designated grower.8 Health Canada, through a contracted grower, provided the strain Cannabis sativa, containing approximately 12% THC with no CBD content.

Concerns about this program were expressed during the following years. Patients disliked the application process and that only one strain of marijuana was available for purchase from Health Canada.9 Other expressed concerns about hazards (humidity, mold, poor air quality), safety (fire hazards due to faulty or overloaded electricity installations), and security (an illicit market, risk of home invasion by criminals) related to the production of marijuana by individuals. Furthermore, rapid growth in the number of authorized users had a significant impact on the administration of the program, leading to long application processing times and high costs. Finally, Canadian courts found parts of the MMAR to be invalid.9

To address these concerns, in 2013 the Canadian Government enacted the Marihuana for Medical Purposes Regulations (MMPR).10 Under the MMPR, Health Canada no longer issues authorizations to possess marijuana for medical purposes to patients. It does, however, licence qualified applicants to produce and distribute marijuana. Licensed producers are required to establish strict regulatory measures relating to good production practices, quality assurance, testing, standardization, security, and distribution. To monitor the use of marijuana, Health Canada requires licensed producers to provide reports to provincial licensing authorities. These reports contain information on the patient, the prescribing heath professional, and the quantity of marijuana authorized.8

Under the MMPR, healthcare practitioners (physicians and nurses) must sign a medical document indicating the daily dose of marijuana and the length of time for which this document is valid.10 Patients should not be asked to pay for this medical document as it is considered similar to a prescription. After obtaining the document, patients can register with the licensed producer of their choice. The licensed producer then must verify with the healthcare professional that the document is legitimate and accurate. The regulations state that patients may not possess more than one month’s amount of marijuana, or a maximum of 150 g, at one time.8 The licensed producer couriers the marijuana to the patient. Since June 2015,11 producers have been allowed to supply marijuana for medical purposes in three forms: fresh, dried, oil (see section 4).

The MMAR and MMPR operated in parallel for a transition period from June 2013 until the end of March 2014. Thus, the MMPR replaced the MMAR as of 1 April 2014 and is in operation today.12 Following this transition period, individuals were not supposed to produce their own marijuana. This part of the regulation, however, was suspended by a British Columbia Court of Appeal to allow patients who were unable to afford marijuana from a licensed producer to continue to grow their own.8 Until another decision is rendered, patients who had valid authorization to possess marijuana as of 31 March 2014, as well as authorization for personal-use production or designated-person production, have had their authorizations extended.8

Provincial licensing authorities guidelines and policies

Based on the absence of scientific evidence, provincial and territorial licensing authorities recommend caution when prescribing a substance without knowing its risk and benefit. Specific provincial regulations are listed in Table 1.13-24

Table 1 Provincial licensing authorities’ regulations on medical cannabis
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Marijuana available on Canadian market (companies, plants, mode of delivery)

Under the current MMPR, production of medical marijuana by individuals is illegal. Health Canada has licensed authorized producers across the country, limiting the production to specific license types, such as “Cultivation Only,” “Sale Only,” or “Cultivation and Sale” of the various marijuana products, including dried marijuana plant material, fresh marijuana, and cannabis oil. There are 26 authorized licensed producers (as of October 23, 2015) located in seven provinces in Canada who hold a valid license from Health Canada and are supplying dried medical marijuana to the Canadian population25 (Table 2). These licensed producers offer more than 200 strains of dried marijuana (with additional strains coming soon), including various strains of cannabis such as Cannabis sativa, Cannabis indica, or hybrid forms. In addition, they offer dried marijuana with diverse THC/CBD content ratios and mixed strains. Thus, the government’s decision to transfer marijuana production to licensed producers has increased the diversity of products available for patients because the current MMPR does not limit the marijuana strains that can be cultivated or their THC/CBD content ratio.

Table 2 Dried marijuana products available for purchase from the Canadian Licensed Producers approved by Health Canada
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With such a diversity of products, patients may be challenged when choosing the best product for their particular medical condition. Although some authorized producers offer a customer service line to help patients select the appropriate strain based on the THC/CBD content ratio, patients may prefer to select a local authorized producer or strains they can afford (licensed producers have the liberty to set their own price). The price for the dried marijuana plant material is currently in the range of $5 to $15 per gram.

There is little information to guide physicians and patients as to the appropriate product and/or THC/CBD ratio to use for a specific medical condition. Most patients therefore select their strain based on their symptoms and disease and the benefits they want to experience as well as the time of the day they are using the marijuana. For example, some strains of marijuana present a very high CBD but low THC content ratio, which is associated with little or no psychoactive effects. These products may be suitable for symptom relief in patients who prefer to avoid the psychoactive effect to maintain their daily routine.

Currently, Health Canada has not provided any precise dose or established a uniform dosing schedule for medical cannabis because it is not an approved therapeutic drug in Canada. However, to help physicians and nurse practitioners (authorized by provincial licensing authorities) to prescribe medical cannabis, they provide a Daily Amount Fact Sheet (Dosage) document to assist the practitioner determine a safe, effective dose.26 This document clearly states that “dosing remains highly individualized and relies to a great extent on titration (i.e., finding the right dose where potential therapeutic effects are maximized while adverse effects are minimized).” It is also noted that “various surveys published in peer-reviewed scientific literature suggest that the majority of people using smoked or orally ingested medical cannabis reported using approximately 1-3 g of dried marijuana per day.” Dried marijuana can be inhaled through smoking, vaporizing, or oral administration. Smoking cannabis results in a more rapid onset of action, higher blood levels of cannabinoids, and a shorter duration of pharmacodynamic effects compared to oral administration. Vaporization presents several advantages, such as formation of a smaller quantity of toxic by-products and more efficient extraction of THC from the dried material.27,28

In addition to dried marijuana, Health Canada has authorized some of the licensed producers to produce fresh marijuana buds and leaves and/or cannabis oil with the intention of permitting their sale in the future. Furthermore, patients who already have a prescription to purchase dried medical marijuana will be permitted to buy fresh marijuana or cannabis oil without an additional prescription. These new forms of cannabis, which will be available for purchase in a few months, will allow patients who do not want to, or are not able to, inhale or vaporize the dried herb to relieve their symptoms using these alternative products.

Currently, with more than 200 strains of dried marijuana available, and fresh marijuana and cannabis oil products becoming available soon, Canadian patients will be, more than ever, able to find a good fit from the diversity of products offered. In turn, their symptoms will be managed and the burden of their disease eased.

Update on clinical studies on cannabis and pain

Recent advances in cannabinoid pharmacology have resulted in increasing attention to the therapeutic potential of cannabinoids. A number of preparations have been or are being developed and investigated in randomized clinical trials. The difficulties encountered when conducting a clinical trial on pain include the fact that pain is a subjective experience. Patients with pain comprise a heterogeneous group with different syndromes and a variety of physical, psychological, and social problems.29

It would be outside the scope of this article to review all the trials published on medical cannabis and pain, but some excellent recent reviews have been published.2-5 We now summarize these recent reports to consolidate our current understanding of the effects of cannabinoids in pain management. To do so, we update two published reviews of acute2 and chronic3 pain trials and comment on cancer-related pain.

Acute pain

A variety of compounds were used in these acute pain studies, including marijuana, cannabis extracts, THC, nabilone, dronabinol, and levonantradol. These cannabinoids are not very effective in alleviating acute pain. This conclusion is based on studies conducted in the postoperative setting (five studies) and in human volunteers (13 studies) between 1977 and 2008.2 In addition, in some cases, administration of cannabinoids, especially in high doses, is associated with increased pain.30-33 However, small numbers of patients have been studied, and the doses used may not have been adequate in postoperative patients. No new study on this particular subject has been published since 2008. However, a prospective, randomized study published in 201334 was carried out in 73 patients undergoing elective operations. The authors focussed on postoperative analgesia in Jamaican cannabis users (n = 42) compared to non-users (n = 31). They showed that cannabis users required significantly more opioid rescue analgesia and had higher pain scores during the immediate postoperative period than non-users. Also, female cannabis users required significantly more analgesia than male users.

The combination of THC and CBD administered in an oromucosal spray (nabiximols) in postoperative patients who cannot take oral medications after abdominal or major surgery has never been tested. Hence, it is unknown whether it has therapeutic potential. A large multicenter study of patients undergoing surgery with a reproducible painful condition and using THC/CBD spray is needed before any conclusion can be drawn regarding the effect of cannabinoids in postoperative pain management.2

Chronic non-cancer-related pain

Cannabinoids are, on the whole, effective for treating chronic pain conditions.3-5 Up to 2010, a total of 18 trials were reported in a systematic review by Lynch and Campbell.3 Their review showed a modest analgesic effect in patients with chronic non-cancer-related pain. Overall, 13 of the trials focussed on neuropathic pain and the other five trials on other types of pain. Several trials reported significant improvements in sleep, and there were no serious adverse events reported.3

Since 2010, eight new studies have been published35-42 (Table 3). Seven of them were performed on patients with neuropathic pain and one on patients with chronic headache. Only one clinical study showed negative results.35 It was on patients with painful diabetic neuropathy treated with nabiximols for ten weeks. Depression, however, was identified as a major confounder of the study’s outcomes. Patients with depression had higher baseline pain scores and were also more likely to respond favorably to intervention, regardless of whether it was nabiximols or placebo administration. Another study looked at cannabinoid-opioid interaction in 21 patients with mixed chronic pain admitted for a five-day inpatient stay.43 Participants were asked to inhale vaporized cannabis three times a day. The vaporized cannabis augmented the analgesic effects of opioids without significantly altering plasma opioid levels. This combination may allow opioid treatment at lower doses with fewer side effects.

Table 3 Clinical trials (2010-2015) on the treatment of chronic non-cancer-related pain with cannabinoids
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In conclusion, 26 clinical trials of good or excellent quality have been published, half of them in patients with neuropathic pain. In all, 11 trials used nabiximols, six used inhaled cannabis (either smoked or vaporized), six used nabilone, two used dronabinol, and one used ajulemic acid (CT-3). Almost of all of these studies, including a substantial number of patients (1,364 patients completed the studies), showed that cannabinoids were effective in alleviating pain, especially neuropathic pain. In other treatment outcome assessments of chronic pain, cannabinoids were effective in relieving pain in patients with musculoskeletal disorders, fibromyalgia, pain associated with human immunodeficiency virus (HIV) infection, and other chronic pain conditions. It should be noted that, overall, drug-related adverse effects were generally well tolerated. They were transient or mild to moderate and most commonly consisted of sedation, dizziness, dry mouth, nausea, and disturbances in concentration. Ware et al. (2015)44 conducted a prospective cohort study to describe safety issues among subjects with chronic non-cancer-related pain who were given a standardized herbal cannabis product (12.5% THC) for a one-year period. Their controls were subjects with chronic pain from the same clinics but who were not cannabis users. The authors showed that 215 individuals with chronic pain recruited to the cannabis group and 216 controls showed no difference in the risk of serious adverse events. Medical cannabis users were at increased risk of non-serious adverse events, most of which were mild to moderate. Finally, there were no differences in secondary safety assessments including pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver, and endocrine function.

Cancer-related pain

Cancer-related pain is a common problem, and 70-90% of patients with advanced cancer experience significant pain.45 Cannabinoids have been tested in this difficult clinical situation. Four studies that were performed more than 35 years ago evaluated the role of cannabinoids in relieving pain associated with cancer using THC or a nitrogen analogue of THC.46-49 Three of these trials demonstrated that THC was analgesic and well tolerated despite its sedative side effect.46-48

Two clinical trials have been recently published in patients with cancer-related pain.50,51 One study compared the efficacy of THC-CBD and THC oromucosal spray with placebo in regard to relieving the pain of patients with advanced cancer.50 In 177 patients with cancer-related pain who experienced inadequate analgesia despite chronic opioid dosing, the mean pain score was significantly in favor of THC-CBD compared with placebo, whereas the THC group showed no change. Twice as many patients taking THC-CBD showed a reduction of more than 30% from the baseline pain scores when compared with placebo. Furthermore, no significant group differences were found in sleep quality or nausea scores. An open-label extension study investigated the long-term safety and tolerability of THC-CBD oromucosal spray in patients with cancer-related pain.52 This study showed that the long-term use of THC-CBD spray (median duration of treatment 25 days, minimum two days, maximum 579 days) was generally well tolerated, with no evidence of a loss of effect for the relief of cancer-related pain with long-term use. Furthermore, patients who kept using the study medication did not seek to increase the dose of the THC-CBD spray or other pain-relieving medication over time.52

In another randomized, double blind, placebo-controlled, graded-dose study of 360 patients (263 completed the study), nabiximols was found to be a useful add-on analgesic for patients with opioid-refractory cancer-related pain.51 The authors verified the efficacy and safety at a low dose (1-4 sprays/day) and a medium dose (6-10 sprays/day) but not at a high dose (11-16 sprays/day), at which point it was not well tolerated.

In conclusion, chronic and unrelieved pain associated with cancer can cause significant distress and disability. The available literature has been valuable in providing insight into the long-term benefit, safety, and tolerability of oral THC and THC-CBD spray in these patients.

Guidance (a practical approach) for the use of medical cannabis

Evaluating a patient for a trial of cannabis for medical purposes

Prudent medical practice incorporates comprehensive evaluation of a patient when new therapies are considered. The following recommendations concerning evaluation and management are similar to those published by the College of Family Physicians of Canada titled Authorizing Dried Cannabis for Chronic Pain or Anxiety,53 the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain published by the National Opioid Use Guideline Group,54 and the Canadian Pain Society’s Guidelines for the Use of Cannabinoid Compounds in Chronic Pain.55

Essential elements of the evaluation and management include the following.

  1. 1.

    Medical history and physical examination

  2. 2.

    Assessment of pain or other symptoms to be treated, identification of any active diagnoses, and ensuring that they are under optimal management

  3. 3.

    Assessment of psychological contributors and risk of addiction or substance abuse

  4. 4.

    Documentation of any history or current use of illicit or non-prescribed drugs, including cannabis and synthetic cannabinoids

  5. 5.

    Determining the effect of previous use of cannabinoids for medical purposes

  6. 6.

    Consideration of urinary drug screening to assess current use of prescribed and non-prescribed medication

  7. 7.

    Setting goals of treatment with cannabis - e.g., pain reduction, increased functional abilities, improved sleep quality, increased quality of life, reduced use of other medications56

  8. 8.

    Development of a treatment plan incorporating these goals

  9. 9.

    Discussion of possible side effects that might be experienced with cannabinoid use (e.g., CNS, cardiovascular, respiratory)

  10. 10.

    Discussion of the risks of addiction

  11. 11.

    Development of a follow-up schedule to review the patient periodically

  12. 12.

    Determining whether the goals of treatment are being achieved and the appropriateness of the response

  13. 13.

    Monitoring for potential misuse or abuse (being aware of clinical features of cannabis dependence57

  14. 14.

    Development of a treatment strategy, particularly for a patient at risk

  15. 15.

    Maintaining an ongoing relationship with the patient

Provincial licensing authorities and professional societies

At all times, the practitioner should be familiar with, and follow the regulations of, the provincial licensing authority.24,53 As a general rule, authorization of medical cannabis is considered a medical act. Examples are as follows.

  • Nova Scotia – “The College considers the authorization of marijuana for medical purposes to be comparable to prescribing medication” and “… authorization of marijuana for medical purposes to be a clinical act and insured service”20

  • Ontario – “… medical document required under the MMPR is equivalent to a prescription” and “… must comply with … the expectations and guidelines that are set out in the College’s Prescribing Drugs policy”17

  • British Columbia – “The College considers the medical document authorizing patient access to marijuana to be equivalent to a prescription”13

Many of the licensing authorities advise consideration of a treatment agreement and/or completion of a consent form (i.e., Saskatchewan,15 British Columbia,13 Quebec.18 In addition, it would also be prudent to follow recommendations and/or guidelines of relevant professional societies - i.e., College of Family Physicians of Canada (CFPC),53 Canadian Pain Society.55

As a general rule, practitioners are advised through these directives and other published documents (mentioned above) first to consider adequate trials of other pharmacologic and non-pharmacologic therapies appropriate to the medical condition being treated. It would also include adequate trials of prescription pharmaceutical cannabinoids. The practitioner authorizing medical cannabis should be primarily responsible for managing specific medical condition(s) for which cannabis is being used.53 As in other areas of medicine, it can be appropriate for specialist practitioners to provide recommendations to the primary care provider if asked for advice.

Contraindications and cautions

There are several recommended contraindications to, and cautions about, the use of medical cannabis.53,54,57-63

Contraindications include the following.

  • Age under 25

  • Personal or family history of psychosis and schizophrenia

  • Current or past history of cannabis use disorder

  • Active substance use disorder

  • Significant cardiovascular or respiratory disease

  • Pregnancy or breast-feeding

Cautions include the following.

  • Concurrent active mood or anxiety disorder

  • Use of tobacco

  • Risk factors for cardiac disease

  • Heavy user of alcohol, opioids, and/or benzodiazepines

Harm reduction

Harm reduction53-55,64-66 should always be considered when authorizing medical cannabis and should include advice about: (1) route/delivery mode: oral/vaporization/smoking; (2) side effects; (3) driving and operating heavy machinery.

Dosing

The basic dosing principle is to “start low and go slow.”53,56 Ware and Desroches noted that “with herbal cannabis, prudence suggests a “start low, go slow” strategy using non-smoking delivery mechanisms, quality-controlled products, and the lowest level of THC required to achieve therapeutic aims and minimize side effects.”56

Reasonable doses are considered to be up to 1-3 g·day−1.37,44,67 Doses > 5 g·day−1 warrant careful review.56 When the inhaled route is used,the practitioner should give the following advice (adapted from CFPC preliminary guidance).53

  1. 1.

    Consider vaporized over smoked cannabis.

  2. 2.

    Use inhaled cannabis in a well-ventilated, private, calm environment.

  3. 3.

    Use the lowest effective level of THC available.

  4. 4.

    Start any new cannabis product with a slow, single inhalation. Then, wait four hours to appreciate the effects fully.

  5. 5.

    Allow several single inhalation trials of a product to observe and then discuss their responses with the physician, before increasing the number of inhalations or changing the product.

  6. 6.

    Inform and alert the patient about cannabis’s potential mood altering, euphoric, and/or sedative effects.

  7. 7.

    Encourage patients to keep notes on effects and experiences with the therapy to facilitate discussion with the authorizing physician/health professional.

Documentation

Documentation is essential to show that the patient has been evaluated. It also displays the rationale for the use of medical cannabis in the context of the overall management plan and the periodic review of the patient’s status.

An algorithm for the treatment of chronic pain with medical cannabis is provided in the Figure. Common side effects associated with the use of medical cannabis are detailed in Table 4.

Table 4 Common important side effects of cannabinoids (adapted with permission from the Canadian Pain Society’s guidelines for the use of cannabinoid compounds in chronic pain)55,76
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Discussion

Although the pharmacological effects of cannabis have been exploited for nearly 5,000 years for medicinal purposes, it is only during the last decades that crucial scientific discoveries have been made about cannabinoids.68 THC is an agonist to two major cannabinoid receptors (CB1 and CB2), which have their own endogenous agonists (endocannabinoids). These agonists are of central physiological importance, with direct biological effects modulating an array of neurotransmitter systems.69 The cannabinoids available to treat certain disorders include mainly phytocannabinoids (with varying THC and/or CBD contents) and synthetic cannabinoids, such as nabilone, dronabinol (withdrawn from the market), and nabiximols (THC-CBD extracts).

One in five Canadians lives with chronic pain. The costs associated with chronic pain are higher than those for cancer, heart disease, and HIV combined. Estimates place direct health care costs in Canada at more than $6 billion per year, and productivity costs related to job loss and sick days are at $37 billion per year.70 For many patients, current pain management interventions, including drug treatment, are insufficient to provide adequate pain relief and are associated with adverse health and societal effects. In this context, many with chronic pain are turning to other therapies including cannabinoids.71

The legal status of cannabis worldwide varies among countries. One country (Uruguay) and several US states have made herbal cannabis fully legal. More importantly, four countries, including Canada (together with Israel, Czech Republic, and The Netherlands) have or had formal research programmes.72 The Health Canada’s Medical Marihuana Research Program was in place in 2001 but was abolished in 2006 because of budget restrictions, having funded only two clinical studies.44,73 Unfortunately, as the number of patients accessing cannabis-based therapies has increased, research has not expanded.74 Many countries (Austria, Belgium, Germany, Italy, Spain and more that 20 US states) have explicit exemptions for prescribed medical cannabis.

Canada is ahead of many other countries, having had federal regulations that allow patients to access herbal cannabis with a doctor’s authorization since 2001.74 In Canada, however, “cannabis (marijuana, marihuana) is not an approved therapeutic substance and has not been issued a notice of compliance by Health Canada authorizing sale in Canada.”28 Many changes have occurred in recent months in Canada regarding the way medical cannabis is being reorganized. Health Canada has licensed authorized producers across the country but, more importantly, it has decided to be less involved in how medical cannabis is used. The licensing authorities in each province/territory have put in place regulations concerning the use of medical cannabis (see New Canadian regulation on medical cannabis). Under this new system, where producers are licensed to grow and distribute various strains of cannabis, the patient population has reached almost 24,000 in mid-2015, and approximately 4,000 physicians have completed the medical documentation concerning cannabis.74 This leads to a need for educational programs for practitioners and for companies to share the information they receive from patients about benefits and side effects in regard to various medical conditions. The rapid changes surrounding the medical use of cannabis has had a considerable impact on healthcare practitioners, who currently receive little or no education on issues regarding medical cannabis.75 Some authors74 proposed a “cannabis curriculum” that covers botanical, physiological, clinical, and legal issues to allow healthcare practitioners to engage in discussions with their patients and colleagues. As a result of this lack of education nationwide, patients are at the moment nearly left alone to decide which product to use, how often, and at what dose. It is crucial that health practitioners obtain adequate training and that each province monitor the patient’s health when cannabis is prescribed. Such a system is already in place in Quebec, with the building of a database (Quebec Cannabis Registry) that can be used as a research tool.18

Many of the clinical trials investigating the efficacy of cannabinoids for pain relief have been reported during the past decade. Based on a 2015 systematic review and meta-analysis, Whiting et al. 5 reported that there was moderate-quality evidence to support the use of cannabinoids to treat chronic pain and that most trials suggested that symptom alleviation was associated with cannabinoids. These associations, however, did not reach statistical significance in all studies. It is interesting to note that several trials also showed improvement in secondary outcomes such as sleep, muscle stiffness, and spasticity. We did not include clinical trials performed in patients with multiple sclerosis when the primary outcome was not pain, but this subject also was recently reviewed.5

Adverse effects most frequently reported are fatigue, dry mouth, somnolence, and dizziness, but they are of mild to moderate severity and are generally well tolerated. Administration of cannabis and cannabinoids do put the patient at an increased risk of short-term adverse events. These findings are detailed in a recent prospective cohort study of one year that described safety issues among subjects with chronic non-cancer-related pain.44 In the cannabis group, the most common serious adverse events were abdominal pain (12%), intestinal obstruction (12%), and nephrolithiasis (12%). The most common non-serious adverse events were nervous system (20%), gastrointestinal (13.4%), and respiratory (12.6%) disorders. Furthermore, the authors showed that herbal cannabis, when used by cannabis-experienced patients as part of a monitored treatment program, seems to have a reasonable safety profile. The authors suggest that longer-term monitoring for functional outcomes is needed.

Conclusion

We present the new Canadian regulations concerning the use of cannabis for medical purposes. We also report provincial licensing authorities’ regulations on medical cannabis and the various dried marijuana products available for purchase from the Canadian Licensed Producers approved by Health Canada as well as the upcoming alternative products. We also provide guidance for the safe use of medical cannabis and outline how to evaluate a patient for a trial using medical cannabis. Overall, the recent literature supports the idea that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain and possibly cancer-related pain. Despite significant progress in understanding how cannabis and cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to establish acceptable benefit-to-risk ratios.

The science of medical cannabis and the education of healthcare practitioners and patients desperately need to be seen as of greater importance than the development of policy regarding medical cannabis.