Tetrahydrocannabinol

THC acutely increases heart rate and causes orthostatic hypotension. While tolerance develops to cardiovascular effects with repeated use, initial or intermittent exposure in individuals with pre-existing cardiovascular disease may precipitate adverse cardiac events.

Chronic cannabis smoking is associated with symptoms of chronic bronchitis, impaired alveolar macrophage function, and increased susceptibility to respiratory infections. This contraindication applies primarily to the combustion route; vaporization or oral administration may be considered with medical supervision.

THC is strongly contraindicated in individuals with active psychotic disorders or a personal or family history of psychosis. Controlled IV administration produces dose-dependent positive and negative schizophrenia-like symptoms in healthy individuals (D'Souza et al. 2004). The EU-GEI multicentre case-control study found daily high-potency cannabis use (THC ≥10%) conferred an odds ratio of 4.8 for first-episode psychosis. Adolescent-onset use further elevates risk.

THC use in individuals with active substance use disorder risks exacerbation of the existing condition and may complicate recovery. The reinforcing properties of THC via striatal dopamine release create additional dependency risk.

THC is extensively metabolized by hepatic CYP2C9 and CYP3A4. Significant hepatic impairment reduces metabolic clearance, potentially increasing THC exposure and prolonging effects. Dose adjustment or avoidance may be warranted.

THC accumulates in breast milk owing to its high lipophilicity. AAP advises against cannabis use during breastfeeding due to potential exposure of the developing infant.

THC crosses the placenta and accumulates in fetal tissue. Prenatal cannabis exposure is associated with lower birth weight and potential neurodevelopmental effects. ACOG and AAP strongly advise against cannabis use during pregnancy.

Adolescent-onset cannabis use is associated with substantially higher rates of cannabis use disorder (17% vs 9% for adult onset), elevated psychosis risk, and potential long-term cognitive impairment. Animal models demonstrate lasting neurodevelopmental effects from adolescent THC exposure.

THC acutely impairs psychomotor performance relevant to driving and operating machinery. Impairment may persist beyond the perceived duration of acute effects. Blood THC concentrations are poorly correlated with impairment magnitude, making self-assessment of fitness to drive unreliable.