Despite federal prohibition of medical marijuana possession, sale, and use, marijuana use continues to escalate as individual state legalization persists and expands (Table 1). As the medical marijuana landscape rapidly changes, it is imperative that healthcare providers stay up to date on available evidence regarding both the benefits and risks of use. Although it is important to note potential benefits demonstrated in specific disease states, evidence in most qualifying indications is insufficient, with the majority lacking randomized controlled trials (RCTs) (Table 2).

Marijuana and oral cannabinoids (dronabinol, nabilone, oral THC) have been associated with adverse effects, including serious adverse effects as well as study withdrawal. The most commonly reported adverse effects include asthenia, balance problems, disorientation, gastrointestinal effects, euphoria, somnolence, dry mouth, fatigue, hallucinations, paranoia, and agitation [11,17].

Marijuana use has a negative effect on mental health and neurologic function. Marijuana users are at risk for tolerance, dependence, and withdrawal [4,18,44]. Multiple studies have examined the negative effects of marijuana on acute and long-term cognition, including impairment in attention, impulse control, decision-making processes, working memory, and executive function. Additionally, marijuana has been associated with an early onset of psychotic disorders, an exacerbated course of illness in established psychotic disorders, exacerbation of mania in bipolar disorders, and worsened symptoms of PTSD [4,11,18,41,44].

Pulmonary, cardiovascular, and carcinogenic effects of marijuana remain controversial [4,44,48,49]. In vivo and in vitro studies have demonstrated that marijuana inhibits several hepatic enzymes (CYP2D6, CYP2C19, CYP2C9, CYP3A4), and preliminary evidence in humans suggests that marijuana may interact with serum drug concentrations of warfarin and antiretroviral therapies [16,50,51,52]. However, additional research is warranted in these areas as the risk of clinically significant drug interactions is unknown [53].

When discussing medical marijuana use, pharmacists must be knowledgeable about potential benefits and risks. Disease states with substantial evidence include chronic pain, chemotherapy-induced nausea and vomiting (oral cannabinoids only), and patient-reported spasticity in MS [2]. Further research is warranted, particularly regarding products similar to those currently available in dispensaries. Because medical marijuana lacks quality standards and FDA regulation, available products have shown significant inconsistencies, with one study revealing that only 17% of edible cannabis products were accurately labeled [54]. It is the responsibility of prescribers and pharmacists to educate patients on potential adverse events and drug interactions. Other pertinent issues to consider are marijuana dosing as well as the inability to extrapolate evidence between oral cannabinoids and marijuana due to differences in chemical composition. As a result of limited high-quality evidence and lack of regulation, the potential benefits and risks must be weighed carefully to make appropriate clinical decisions.