Priming primary care providers to engage in evidence-based discussions about cannabis with patients

Medical cannabis laws and implementation of programs vary greatly by state, but in many states with medical cannabis laws, physicians can “certify” that a patient has a condition for which cannabis has been indicated and state-administered programs grant certified patients medical cannabis “cards” [2]. The medical cannabis card then allows patients to enter medical cannabis dispensaries where an employee (often referred to as a “budtender” [19]) discusses the various available products. However, most budtenders have little or no medical training [20]. Most of these states also allow limited home cultivation of cannabis for medical purposes. In states in which cannabis is recreationally legal (all of which also have medical cannabis laws), the medical and recreational dispensaries are often in the same store. Of the states with medical cannabis laws, most have legalized cannabis for the following indications: chronic pain, muscle spasticity and/or multiple sclerosis, epilepsy, anorexia/cachexia, HIV/AIDS, glaucoma, cancer, inflammatory bowel disease, and post-traumatic stress disorder (PTSD) [21]. In a recent nationwide review of state registry data, the most commonly listed qualifying conditions for medical cannabis certification were chronic pain, followed by multiple sclerosis, nausea, cancer, then PTSD [22]. Additionally, one survey study in California found that the most common self-reported indications for cannabis use were anxiety, chronic pain, stress, insomnia, and depression [23].

There are many gaps in the evidence examining the health effects of cannabis, though the literature is expanding rapidly. Many studies have been conducted outside the U.S. in part because of regulatory hurdles associated with the status of cannabis as a Schedule 1 controlled substance at the federal level, which designates it as having “no currently accepted medical use and a high potential for abuse” [24]. A recent National Academy of Sciences report provided a broad and high-level overview of contemporary knowledge about the pharmacology, regulation, benefits, and harms of cannabis for a variety of conditions [3]. It concluded that there is “substantial evidence that cannabis is an effective for chronic pain in adults.” [3]. However, the report did not distinguish the evidence for different types of chronic pain, did not use standard systematic review methods and terminology, and also cautioned that little was known about the efficacy and dosing of cannabis preparations available in the United States.

Two recent systematic reviews that focused on the effects of cannabis for chronic pain found limited evidence that cannabis is effective for neuropathic pain (i.e. pain from peripheral or central nervous system lesions) and for multiple sclerosis-related pain and spasticity in studies of short duration, but insufficient evidence to draw conclusions about the effects of cannabis on nociceptive pain (i.e. pain from tissue damage such as from inflammation, trauma or arthritis) [25, 26]. In placebo-controlled trials of patients with neuropathic pain from a variety of causes, cannabis was associated with a small reduction in pain (about 1 point on a 10-point visual analog scale), and more patients treated with cannabis experienced a 30% or more improvement in neuropathic pain than those assigned to placebo [25]. In patients with multiple sclerosis, cannabis formulations with a combination of THC/CBD in a 1:1 or 2:1 ratio were associated with improvements in pain and spasticity at up to 12–15 weeks of follow up [25, 27]. However, there are numerous limitations to this evidence base. First, findings were not consistent across studies. Second, most studies showing benefit reported outcomes after only a matter of hours to days with the longest study being 15 weeks. Providers should be cautious in extrapolating data from short-term studies to the management of chronic pain, which often requires treatment for many months. Third, the formulations tested differed across studies, and often differed from formulations that are commonly available to, and used by, patients in dispensaries [25]. For example, the best studied formulation of cannabis is nabiximols, a cannabis extract that comes as an oromucosal spray of 2.5 mg THC/2.5 mg CBD; while it is licensed in other parts of the world, it is not available in the U.S. In studies that showed a benefit from nabiximols, participants used an average of 25 mg of THC over 24 h [25].

Oral cannabinoids may improve chemotherapy-induced nausea and vomiting [3]. The synthetic, prescription cannabinoids nabilone and dronabinol appear to be as effective in reducing chemotherapy induced nausea and vomiting as older prescription anti-emetics, but the evidence is limited by methodologic flaws, and not representative of currently available anti-emetics and chemotherapeutic regiments. The authors of one review cautiously suggest cannabinoids may be a reasonable second-line option for patients who have failed or cannot tolerate conventional anti-emetics [28].

There are numerous clinical conditions for which cannabis or cannabinoids have been considered or even approved for use at the state level despite a lack of controlled studies in many cases. There is largely insufficient evidence to support or refute the effectiveness of cannabis and/or cannabinoids for the following conditions: irritable bowel syndrome, amyotrophic lateral sclerosis, Parkinson’s disease, dystonia, post-traumatic stress disorder, and glaucoma. There are very few high-quality studies examining the effects of cannabis and oral cannabinoids on weight loss and anorexia associated with HIV/AIDS and cancer. While there is insufficient evidence for the effectiveness of cannabis or cannabinoids for most forms of epilepsy, the FDA recently approved a highly purified CBD plant extract called Epidiolex® for the treatment of two rare childhood-onset epilepsy syndromes on the basis of trials showing significant reduction in seizure frequency [29, 30]. There has been increased interest in additional potential therapeutic effects of CBD alone, in part because it is viewed as likely to have a more favorable adverse effect profile than THC-containing products. While there is not conclusive evidence supporting the health effects of CBD preparations beyond the epilepsy syndromes mentioned above, a growing body of evidence suggests CBD may have potential as an anxiolytic agent, though further research is needed [31, 32].

Pain is a leading symptom driving non-recreational cannabis use, whether medically authorized or not. Despite recent efforts to reduce prescribed opioid therapy for pain in the U.S., and to increase treatment for opioid use disorder (OUD), opioids remain a prominent treatment for both acute and chronic pain, and untreated illicit opioid use has reached epidemic levels [58]. Given widespread opioid and cannabis use, both illegal and prescribed, cannabis and opioid co-use is increasingly common.

There is currently not enough evidence to suggest that the long-term benefits of cannabis are likely to outweigh the harms, though our understanding of the balance of benefits and harms of cannabis is very likely to change as research accumulates. While there is no conclusive evidence to support providers’ endorsement of widespread medicinal use of cannabis, the reality of clinical practice today is that patients have access to and are using cannabis, and it is the provider’s duty to play a role in reducing any likelihood of harm.

When asking patients about cannabis use, it is important to do so in a routine, non-judgmental fashion, and to ask about it separately from illicit drug history because cannabis is legal in many parts of the country. The provider may also want to ask about the reasons for use—whether recreational, medical, or both—because the reason for use may influence its frequency and route of administration; for medical use, this also allows for follow-up to assess whether or not use for medical purposes is having the intended effect [76, 77]. When a provider encounters a patient who uses cannabis, the first step is to determine the quantity, frequency, and route of administration, as well as assessing for CUD. There are no widely validated short CUD screeners, but one option is use of the three-item Cannabis Use Disorders-Short Form to assess for CUD [78], and if the results are positive the provider should follow up by assessing for CUD with DSM-5 criteria (see Table 3).

Treatment of CUD should include evidence-based behavioral therapies, such as cognitive-behavioral therapy and motivational enhancement therapy along with abstinence-based incentives, targeted at cannabis cessation [79]. While a number of pharmacotherapies for CUD have been evaluated—including gabapentin, N-acetylcysteine, antidepressants, and cannabinoids—the evidence is currently not strong enough to support routine use of pharmacotherapy for CUD [80]. For patients who use cannabis, but do not meet criteria for CUD, providers should counsel them on potential harms and provide psychoeducation and behavioral support.

Given the risk of withdrawal with CUD, providers should counsel patients who continue to use cannabis to avoid frequent, heavy use. Indeed, simply outlining the symptoms of withdrawal such as depression, anxiety, insomnia, and restlessness may help patients avoid a dangerous cycle of self-medication for withdrawal symptoms. It is likely that THC in particular is responsible for many of the potential mental health harms, so providers should suggest that patients avoid high-THC products. Patients at risk for mental illness, especially psychotic spectrum disorders, should be counseled to avoid cannabis.

The formulation of cannabis and route of administration influence its potential adverse effects. Patients should be made aware of the potent metabolite and the delayed onset of action associated with edible products, and accordingly use low doses, and avoid rapid dose escalation. Cannabis naïve patients should be especially cautious with edible products, and all individuals should avoid dabbing altogether given the high potency and risk for adverse effects. Individuals should avoid frequent and long-term cannabis smoking, and long, deep breath holds during inhalation. Providers should warn against use of any unregulated product obtained outside of dispensaries, including products advertised as CBD-only, given the existence of dangerous synthetic cannabinoids, labeling inaccuracies, and the risk of severe illness such as vaping-related pulmonary illness.

For patients who are prescribed other central nervous system (CNS)-acting agents, including, for example opioids, benzodiazepines, muscle relaxants, and gabapentinoids, we would encourage prescribers of those medications to caution patients that the additive effect of cannabis on psychomotor slowing and other CNS side effects has not been well studied. We recommend a conservative approach whereby providers decrease CNS-acting agent polypharmacy (in safe, patient-centered ways) prior to or concomitant with patients initiating cannabis regimens.

With the changing landscape of cannabis legislation throughout the U.S., and more states legalizing recreational cannabis, medical providers need to mindfully frame discussions of cannabis use with patients and families. To counter the inaccurate public perception of cannabis as harmless, the medical community must be prepared to synthesize the evidence and deliver clear public messaging on the potential harms of cannabis use. Current evidence suggests that recreational cannabis use is associated with other substance use and SUDs; mental health conditions; impairment in memory, learning and attention; respiratory symptoms; motor vehicle crashes; and overdose injuries in pediatric populations [3, 25, 81]. Conversely, advocates of legalization argue that the criminalization of cannabis has had substantial social justice and public health implications through contact of millions of Americans with the criminal justice system [82]. There were 8.2 million cannabis-related arrests from 2001 to 2010, with African Americans four times more likely to be arrested; most of these arrests were for simple possession [83]. The downstream effects of these arrests can be detrimental as the existence of a criminal record can act as barrier to employment, housing, and public services for those arrested [83]. Ultimately, legalization will help to mitigate some of these structural inequities. However, legalization must be accompanied by a concerted public health effort to counter the potential harms of cannabis use.

This is particularly important for adolescent and young adult populations because we know most harms are related to use of smoked cannabis products among individuals who began smoking in a heavy, habitual way in adolescence. Development of prevention messages geared to adolescents and young adults is vital. Data from the Monitoring the Future study, which is an annual survey of 8th, 10th and 12th grade students in the U.S., suggests that for three decades there was an inverse relationship between perceived risk of cannabis and cannabis use among high school students. Over the last few years, perceived risk has continued to decline steeply but there has not been a concomitant further rise in use, creating an opportunity for the medical community to focus efforts on effective prevention interventions [84].