Cannabis Use Disorder

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Description

  • Cannabis use leading to clinically significant impairment or distress, manifested by ≥2 of the following symptoms within a 12-month period:
    • Consumption of larger amounts over a longer period of time than intended
    • Persistent desire or inability to cut down or control amount used
    • Inordinate amount of time spent in activities is necessary to obtain, use, or recover from use.
    • Presence of craving for cannabis
    • Recurrent use resulting in failure to fulfill major role obligations at work, school, or home
    • Continued use despite having persistent or recurrent social or interpersonal problems due to cannabis use
    • Important social, occupational, or recreational activities are given up or reduced.
    • Recurrent use in physically hazardous situations
    • Continued use despite knowledge of a persistent physical or psychological problem caused or exacerbated by cannabis
    • Tolerance defined by using increased amounts of cannabis to achieve the desired effect or intoxication or diminished effect with continued use of the same amount
    • Withdrawal occurs following cessation of prolonged use, and has at least three behavioral symptoms such as anxiety, restlessness, depression, irritability, insomnia, odd dreams, or physical symptoms such as tremors and/or decreased appetite.
  • According to DSM-5-TR, cannabis use disorder (CUD) is defined as being mild, moderate, or severe based on presenting symptoms; mild: 2 to 3; moderate: 4 to 5; severe: ≥6

Epidemiology

  • The WHO ranks the United States first among 17 European and North American countries for prevalence of cannabis use.
  • It is estimated that 4.5 to 7.0 million persons in the United States meet criteria for CUD.
  • Chronic pain remains the most common reason for medical cannabis licensure. 10–30% of lifetime cannabis users meet criteria for CUD
  • Cannabis-associated psychosis is associated with high-potency cannabis.
  • >90% of Americans approve of cannabis for medical use.
  • Carriers of the AKT1 gene is associated with developing psychosis with use of cannabis

Incidence

Around 17.7 million adults reported daily or near-daily cannabis use in 2022. (This surpasses the number of daily alcohol users (~14.7 million).

Prevalence

  • Lifetime prevalence: As of 2019, approximately 46% of U.S. adults report having used cannabis at least once in their life
  • Prevalence in North America (2015): Estimated 11.6% of the population were recent (past year) cannabis users, totaling about 36.7 million people
  • Global prevalence (2013): 128 to 232 million people aged 15 to 65 years used cannabis—equating to 2.7–4.9% of the global population.
  • Meta-analysis across 33 countries (2000 to 2024) demonstrated that in legalized countries, pooled cannabis-use prevalence ~12% (95% CI: 10–14.3%). In non-legalized countries, cannabis-use prevalence was lower, at ~5.4% (95% CI: 4.3–6.9%)

Etiology and Pathophysiology

  • The two most known therapeutically active cannabinoids in cannabis are δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).
  • THC is the psychoactive component responsible for cannabis’ analgesic, antiemetic, and intoxicating properties. THC concentrations in cannabis have risen over the past 20 years from 4% to 20%. Additionally, high concentration oils and resins are used to increase THC potency.
  • CBD is the nonpsychoactive component responsible for the perceived and experienced antianxiety, antidepressant, antipsychotic, antispastic, anticonvulsant, and antineoplastic properties of cannabis.
  • Strains of cannabis vary, with varying THC/CBD ratios
  • Smoking cannabis results in 25–50% absorption of THC, which rapidly passes into the circulation. The oral bioavailability of THC is much less (3–10%). Effects of smoked cannabis occur within minutes and last several hours; effects from cannabis consumed in foods or beverages appear more slowly, taking 30 minutes to 2 hours to have an effect.
  • Only 5% of those with CUD seek treatment from a health care provider.

Genetics

Studies have identified specific genetic variants associated with an increased risk of developing CUD

GeneFunctionAssociation with CUD
CHRNA2Nicotinic receptor subunitGenome-wide association study data support
CADM2Risk behavior, synaptic functionLinked to impulsivity and cannabis use
FOXP2Brain development, languageInconsistent association with CUD
ANKK1/DRD2Dopamine signalingInvolved in reward and addiction risk
CNR1Cannabinoid receptor (CB1)Direct link to THC effects
ARID1BNeurodevelopmental processesRare variants linked to CUD

Risk Factors

  • Individuals 18- to 29-year-olds, are at more risk for severe CUD.
  • Higher potency cannabis use increases risk of CUD and increases severity of symptoms.
  • Frequency of use affects risk of CUD; monthly users are at 4-fold increased risk, weekly users at 8-fold and daily users at 17-fold increased risk
  • Family history of chemical dependence, comorbid psychiatric disorders, other substance use (i.e., alcohol, tobacco). Lower educational achievement (rates of dependence are lowest among college graduates); low socioeconomic status and ease of acquisition of cannabis and synthetic versions of cannabis
  • Among youths with mood disorders, CUD is a risk marker for nonfatal self-harm, all-cause mortality, and death by unintentional overdose and homicide.

Commonly Associated Conditions

  • Mood disorders
  • Anxiety disorders
  • Cannabis hyperemesis syndrome (CHS)

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