Clinical Safety Reference

A quick-reference guide for clinicians: contraindications, drug interactions, signs of cannabis use disorder, and when to refer.

Who Should Not Use Cannabis

Absolute Contraindications

  • Personal history of psychotic disorders (schizophrenia, schizoaffective disorder)
  • Pregnancy or breastfeeding
  • Unstable cardiovascular disease
  • Under 25 with first-degree family history of psychosis
  • Active non-cannabis substance use disorder

Use with Caution

  • History of anxiety/panic (THC can exacerbate; consider CBD-dominant products)
  • History of depression (complex relationship — monitor closely)
  • Age under 25 (neurodevelopmental concerns)
  • Respiratory disease (avoid combustion; consider edibles/tinctures)
  • Hepatic impairment (altered metabolism of cannabinoids)

Key Drug Interactions

Cannabis (particularly CBD) inhibits CYP3A4, CYP2C19, and CYP2C9 enzymes. THC is a substrate of CYP2C9 and CYP3A4.

Drug ClassInteractionClinical SignificanceRecommendation
WarfarinCBD/THC inhibit CYP2C9 → increased warfarin levelsHigh — bleeding riskMonitor INR closely. May need dose reduction.
ClobazamCBD inhibits CYP2C19 → increased clobazam/norclobazamHigh — sedation, toxicityRelevant for epilepsy patients on Epidiolex. Dose adjustment needed.
BenzodiazepinesAdditive CNS depression + metabolic inhibitionModerate-HighIncreased sedation risk. Monitor and consider dose reduction.
OpioidsAdditive CNS/respiratory depressionModerate-HighMonitor respiratory function. May allow opioid dose reduction.
SSRIs / SNRIsCYP2C19 inhibition → increased SSRI levelsModerateMonitor for serotonergic side effects. May need SSRI dose adjustment.
Immunosuppressants (tacrolimus, cyclosporine)CYP3A4 inhibition → increased levelsModerate-HighMonitor drug levels closely. Transplant patients at particular risk.
StatinsCYP3A4 inhibition → increased statin levelsLow-ModerateMonitor for myopathy symptoms. Consider lower statin dose.

Signs of Cannabis Use Disorder

Approximately 10% of all cannabis users and ~30% of regular users develop CUD (DSM-5). Watch for these patterns:

  • Using more or longer than intended
  • Unsuccessful attempts to cut down
  • Significant time spent obtaining, using, or recovering
  • Craving or strong urges to use
  • Use interfering with work, school, or home responsibilities
  • Continued use despite social or relationship problems
  • Giving up important activities because of use
  • Use in physically hazardous situations
  • Continued use despite physical or psychological problems
  • Tolerance (needing more for same effect)
  • Withdrawal symptoms when stopping

Severity: Mild (2-3 criteria), Moderate (4-5), Severe (6+). For screening tools and clinical handouts, see our companion site's Screening Tools.

When to Refer

Consider referral to addiction medicine or specialized treatment when:

  • CUD criteria are met and patient is unable to reduce use despite wanting to
  • Co-occurring psychosis or psychotic symptoms emerging with use
  • Suicidal ideation — immediate safety planning required
  • Polysubstance use — concurrent alcohol, opioid, or stimulant use disorder
  • Cannabinoid hyperemesis syndrome — recurrent severe vomiting with hot-water bathing compulsion
  • Patient request — patient expressing desire for more structured help

Useful Clinical Resources

Cannabis and cannabinoids interact with multiple cytochrome P450 enzymes, particularly CYP3A4 and CYP2C19. Clinicians should review potential interactions with any patient using cannabis products, especially those on narrow therapeutic index drugs.

Nasrin et al., Drug Metabolism Reviews, 2021