Cannabis

Cannabis produces tachycardia consistently across all administration routes. Ventricular arrhythmias and myocardial infarction have been reported in the context of smoked cannabis. Cardiac toxicity risk is amplified by co-administration with sympathomimetic agents. Individuals with significant cardiovascular disease face elevated risk of adverse cardiac events.

Asthma, COPD, Immunocompromised (pulmonary aspergillosis risk)

Smoked cannabis preparations are contraindicated in individuals with pre-existing respiratory disease including asthma and COPD. Combustion byproducts cause airway inflammation and bronchitis. Immunocompromised individuals face additional risk of invasive pulmonary aspergillosis from fungal contamination. Vaporised or oral preparations avoid combustion-related respiratory harm.

Personal or family history of psychotic disorders is a strong relative contraindication. Epidemiological evidence consistently supports a dose-response relationship between cannabis use and psychosis risk, with high-potency preparations conferring the greatest risk. Cannabis use functions as a component cause where genetic vulnerability interacts with the precipitating substance. Two case reports document emergent psychosis following high-potency concentrate use in individuals without prior psychiatric history.

THC and CBD are extensively hepatically metabolised. Hepatic impairment is expected to reduce clearance of both cannabinoids, increasing plasma levels and prolonging effects. No specific dose adjustment guidelines exist for hepatically impaired patients using non-pharmaceutical cannabis preparations.

Prenatal cannabis exposure is significantly associated with adverse neonatal outcomes including lower birth weight, increased risk of preterm birth, small-for-gestational-age neonates, and NICU admission. THC crosses the placenta and interacts with fetal cannabinoid receptors. Long-term follow-up studies document subtle but enduring effects on memory and externalising behaviours in offspring. Professional bodies universally discourage cannabis use during pregnancy. No safe threshold has been established.

The developing brain is particularly vulnerable to cannabis exposure. Adolescent cannabis use is associated with enduring cognitive deficits, mesocorticolimbic dysregulation, and schizophrenia-like biomarkers. Epidemiological evidence supports dose-dependent increases in psychosis risk with earlier age of initiation.

Cannabis cannabinoids (THC and CBD) competitively inhibit CYP2C9, the primary enzyme responsible for warfarin metabolism. Co-administration may increase warfarin plasma levels and INR, elevating bleeding risk. Patients on warfarin or other narrow-therapeutic-index CYP2C9 substrates should be monitored closely if cannabis use is initiated or dose changes.

Cannabis cannabinoids noncompetitively inhibit CYP3A4, a major drug-metabolising enzyme. Co-administration with CYP3A4 substrates (midazolam, many benzodiazepines, immunosuppressants, statins) may increase their plasma concentrations. Clinical significance depends on cannabis dose, CBD content, and the therapeutic index of the co-administered drug.

Co-administration of cannabis with other CNS depressants produces additive sedation and psychomotor impairment. With opioids, pharmacodynamic synergism increases analgesic effects but also CNS depression risk. With alcohol, combined use substantially increases driving impairment and crash risk beyond either substance alone. With benzodiazepines, enhanced sedation is expected.