Tetrahydrocannabihexol

Coronary artery disease, Heart failure, Arrhythmias, Uncontrolled hypertension

CB1 full agonism produces dose-dependent tachycardia via sympathetic activation. The full agonist ceiling means cardiovascular stress may exceed that produced by Δ9-THC at equivalent receptor occupancy. Individuals with pre-existing cardiovascular disease face amplified risk of acute cardiac events during intoxication.

Schizophrenia, Schizoaffective disorder, Family history of psychotic disorders

Personal or family history of psychotic disorders represents an absolute contraindication. CB1 full agonism confers elevated risk of acute psychotic episodes compared to Δ9-THC (partial agonist). Higher CB1 efficacy may accelerate onset of schizophrenia-spectrum conditions in predisposed individuals. Japanese adverse event data documented hallucinations among reported symptoms.

Active cannabis use disorder, Cannabis use disorder in remission

THCH's higher potency and full CB1 agonism produce greater reward-circuit activation than Δ9-THC, increasing reinforcement salience and dependence liability. Individuals with active or remitted cannabis use disorder face elevated relapse and escalation risk.

Cirrhosis, Severe hepatic impairment, Active hepatitis

THCH is expected to undergo CYP2C9-dominated hepatic metabolism by analogy with Δ9-THC. Hepatic impairment would reduce first-pass metabolism and clearance, prolonging exposure and potentially intensifying effects. Given the absence of human pharmacokinetic data, the magnitude of this effect is unquantifiable.

Pregnancy, Breastfeeding

CB1 receptors are expressed in fetal and neonatal brain tissue where they regulate neurodevelopmental processes including neuronal migration, axon guidance, and synaptogenesis. Exogenous full CB1 agonism with a compound of unknown pharmacokinetics poses unquantifiable but mechanistically plausible risk to fetal neurodevelopment. Transfer to breast milk is expected given high lipophilicity.

Individuals under 25 years

The endocannabinoid system is under active development during adolescence and into early adulthood. CB1 receptors regulate synaptic pruning, myelination, and cortical maturation. Exogenous full CB1 agonism with a compound more potent than Δ9-THC may disproportionately disrupt these neurodevelopmental processes compared to conventional cannabis use.

Alcohol co-administration, Benzodiazepine co-administration, Opioid co-administration

Concurrent use of CNS depressants produces additive sedation and, with opioid co-administration, elevated respiratory depression risk. Japanese adverse event data documented prolonged unconsciousness — synergistic CNS depression with co-intoxicants could worsen this outcome. The margin between recreational dose and dangerous synergistic depression is narrower than for Δ9-THC.