Am Fam Physician. 2021;104(6):598-608
Related Editorial: Counseling Parents and Adolescents About Marijuana
Related Letter to the Editor: Cannabis Use During Pregnancy
Patient information: See related handout on talking points about marijuana for parents and teens.
Author disclosure: No relevant financial affiliations.
Cannabis use in the United States is increasing annually in people of all ages. This increase is fueled by state-level legalization, decreased risk perception, and increased social acceptability. Cannabis and its active components, cannabinoids, have been studied for medical uses and marketed in many commercial forms. Cannabis can impair short-term memory, judgment, and coordination, and there is substantial evidence that it can adversely affect multiple organ systems. Cannabinoids have potential adverse drug interactions with commonly prescribed analgesic, psychotropic, and cardiovascular medications. Current evidence supports cannabinoid use only for a limited number of conditions (chemotherapy-induced nausea and vomiting, specific pain and spasticity syndromes, and certain forms of childhood epilepsy); thus, physicians recommending cannabinoids need to weigh the potential harms vs. perceived benefits. The U.S. Preventive Services Task Force recommends universal screening for unhealthy drug use, including cannabis, in adults 18 years and older. However, the American Academy of Family Physicians does not support this recommendation because of the lack of evidence of benefit in screening patients for unhealthy drug use, except for opioid use disorder. Treatment of cannabis use disorder is largely behavioral and requires a patient-centered, multifaceted approach with a focus on patient education. Pharmacotherapy for cannabis use disorder is limited and experimental. Harm reduction strategies and education about cannabis withdrawal syndrome should be provided to patients. Interpretation of urine drug testing for cannabis is challenging because of the persistence of metabolites for four to five days after a single use and for one month after chronic daily use.
Legalization of cannabis in 36 U.S. states and the District of Columbia has transformed a once illegal drug into an over-the-counter remedy for numerous ailments.1 Cannabis has become a multibillion-dollar industry with approximately 15% of U.S. adults reporting cannabis use in 2017.2 Cannabis risk perception among U.S. adolescents and adults has steadily decreased in the past two decades, accompanied by an annual increase in cannabis use among these populations.2–4 Between 2002 and 2012, the percentage of adults 18 to 29 years of age reporting cannabis use within the previous year doubled from 10.5% to 21.2%.5 The 2017 Monitoring the Future survey found that the annual prevalence of cannabis use for 12th graders was 37.1%.6
| Clinical recommendation | Evidence rating | Comments |
|---|---|---|
| Patients with a personal or family history of psychotic disorders should avoid cannabis because of an increased risk of psychosis.7,31,32 | A | Systematic review and consistent evidence from RCTs |
| Cannabis should be avoided in pregnant and lactating patients because of potential risks to the infant.34,35 | C | Expert opinion and consensus guideline |
| Patients with long-term opioid use should avoid concurrent cannabis use.38–40 | B | Evidence from RCTs showing potential for some harm and unclear benefits |
| Cannabinoids should be considered as a third-line option for neuropathic pain if benefits outweigh risks.41 | B | Consistent evidence from RCTs and systematic reviews |
| Cannabinoids should be considered as second-line therapy for chemotherapy-induced nausea and vomiting.42 | B | Consistent, moderate-quality evidence from RCTs |
| Patients with cannabis use disorder should be offered a combination of psychosocial interventions.46 | B | Systematic review |
Cannabis use disorder develops in 19.5% of lifetime users.7 Adolescents are two to four times more likely than adults to develop cannabis use disorder within two years of use.8 A 2017 national survey showed that 22% of Americans incorrectly believe marijuana is not addictive, and 29% strongly believe that its use can prevent health problems.9
Figure 1 presents an approach to the management of patients who use cannabis.
Definitions
CANNABIS AND CANNABINOIDS
The Cannabis sativa plant contains more than 100 chemical structures called cannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD).10 THC has euphoric effects, whereas CBD is not psychoactive at typical doses.10,11 Marijuana and hemp are different strains of the same plant, the latter containing less than 0.4% of THC.10 Commercial marijuana commonly refers to the dried flowers (buds) and leaves of the C. sativa10 plant and is often cured in mason jars (Figure 2). The potency of THC in cannabis has been rising since the 1970s because of selective breeding. The average THC content of a cannabis joint rose from 1.5% in the 1970s to 8.9% in 2008 and 21% in 2018.12
Table 1 summarizes common types of cannabis products and methods of use.10,11 Smoking involves a bud or resin plus a device such as rolled paper, a pipe, or a bong. Vaping involves a bud, resin, or liquid solution placed in a heating device. Dabbing involves inhaling a potent concentrate high in THC. Edibles are available in many formulations (Figure 3).
| Form | Other names | Methods of use | Comments |
|---|---|---|---|
| Concentrate (high THC) | Wax, shatter, dab, butane hash oil | Dabbing (inhale) | Dab (< 1 cm) placed on hot metal rod; THC concentration may be up to 90%; may cause explosion |
| Edibles (THC and CBD) | Gummies, teas, brownies, candies, infused drinks | Oral consumption | Butter/oils used to extract cannabinoids; many possible formulations |
| Marijuana | Bud, flower | Smoking, vaping | Often purchased as an eighth (3.5 g), with a typical joint containing 0.5 g to 1 g; THC concentration is 5% to 20% |
| Oils (THC and CBD) | Hash oil, honey oil, cannabis oil, CBD oil | Topical | Alcohols and other solvents used for extraction; dangerous if inhaled; THC concentration is 15% to 50% |
| Resin | Hash, dry sift | Smoking, vaping | Concentrate is made from trichomes (flower protrusions); THC concentration is 2% to 8% |
| Tincture (THC and CBD) | Tincture of cannabis, green dragon, CBD tincture | Oral consumption, sublingual, topical | Ethanol used for extraction |
| Vape pen | Vape juice, e-juice, e-liquid | Vaping | Similar to electronic cigarettes except contains THC concentrate, tinctures, or oils |
THE ENDOCANNABINOID SYSTEM
Cannabinoids act via the endocannabinoid system. The endocannabinoid system is involved in many physiologic processes with two main receptors: CB1 and CB2.10,13 Two endogenous cannabinoids, anandamide and 2-arachidonoylglycerol, bind these receptors. Gamma-aminobutyric acid and glutamate are involved in these neural pathways as inhibitory and excitatory neurotransmitters, respectively (Figure 4).10,13 THC mimics endogenous cannabinoids by stimulating CB1 and CB2 receptors in the central nervous system, whereas CBD stimulates serotonin 5-HT1A receptors.10,13
SYNTHETIC CANNABINOIDS
Three cannabinoid medications have been approved by the U.S. Food and Drug Administration (FDA). Dronabinol (Marinol) and nabilone (Cesamet) were approved in 1985 and 2006, respectively, for chemotherapy-induced nausea and vomiting.10 CBD (Epidiolex) was approved in 2018 for rare forms of childhood epilepsy.10,14 Nabiximols (Sativex) is approved in 28 countries, including the United Kingdom and Canada, but has not received FDA approval. Cannabinoid medications are summarized in (Table 2).10
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