Δ-8-Tetrahydrocannabinol

Coronary artery disease, Cardiac arrhythmias, Recent cardiovascular events

Δ8-THC activates CB1 receptors, producing tachycardia via peripheral sympathetic activation and subsequent bradycardia via central mechanisms, along with blood pressure changes. These hemodynamic effects may be clinically significant in patients with coronary artery disease, arrhythmias, or recent cardiovascular events. No Δ8-THC-specific cardiovascular safety data exist; risk is inferred from Δ9-THC cardiovascular pharmacology.

Schizophrenia, Schizoaffective disorder, First-degree family history of psychotic illness

CB1 agonism by Δ8-THC can precipitate or exacerbate positive psychotic symptoms including paranoia and derealization. Individuals with schizophrenia, schizoaffective disorder, or a first-degree family history of psychotic illness are at elevated risk. No Δ8-THC-specific psychosis data exist; this contraindication is inferred from the extensive Δ9-THC literature on cannabis-induced psychosis. Lower CB1 affinity may attenuate but does not eliminate this risk.

Moderate-to-severe hepatic impairment, Cirrhosis

Δ8-THC undergoes extensive first-pass hepatic metabolism (oral bioavailability ~3% in rats reflects heavy hepatic extraction). Impaired hepatic function would alter CYP-mediated clearance, potentially increasing systemic exposure and prolonging effects. The active metabolite 11-OH-Δ8-THC formation may also be affected. No Δ8-THC-specific hepatic impairment data exist; risk is inferred from pharmacokinetic profile and Δ9-THC analogy.

Pregnancy, Breastfeeding

Δ8-THC is a highly lipophilic compound that crosses the placental barrier and is present in breast milk, as documented for Δ9-THC. The endocannabinoid system is involved in embryonic neurodevelopment, and exogenous CB1 agonism may disrupt these processes. Developmental effects documented for Δ9-THC are expected to apply. No Δ8-THC-specific reproductive safety data exist.

Children under 18 years, Particularly children under 6 years

Pediatric exposure to Δ8-THC is a documented public health concern with substance-specific evidence. 41% of 2,362 poison control exposures involved patients under 18 years. Multiple pediatric patients have presented to emergency departments unconscious and unresponsive after ingesting Δ8-THC edible products. Children under 6 years are particularly vulnerable to serious adverse events. This is the only absolute contraindication supported by substance-specific (not class-inferred) data.

Warfarin therapy, Other CYP2C9-dependent anticoagulants

Δ8-THC is expected to be metabolized via CYP2C9 (inferred from Δ9-THC), creating potential for pharmacokinetic interaction with warfarin, a narrow-therapeutic-index CYP2C9 substrate. Co-administration may increase warfarin exposure and bleeding risk. No Δ8-THC-specific drug interaction studies have been published; this interaction is predicted from Δ9-THC CYP metabolism data.