HHC

Ischemic heart disease, Arrhythmias, Heart failure

Cardiovascular disease is a relative contraindication. CB1 agonists produce tachycardia and vasodilation; patients with ischemic heart disease, arrhythmias, or heart failure face increased risk of adverse cardiac events. No HHC-specific cardiovascular data exist — this is inferred entirely from the CB1 agonist class profile of Δ⁹-THC.

Schizophrenia, Schizoaffective disorder, Family history of psychotic disorders

Personal or family history of psychotic disorders is an absolute contraindication. CB1 agonism is an established risk factor for precipitation and exacerbation of psychotic illness. Ireland's European Web Survey on Drugs documented reports of psychotic illness precipitated by HHC use, providing field-level support beyond class inference alone.

Panic disorder, Generalized anxiety disorder

Anxiety disorders are a relative contraindication. HHC demonstrated dose-dependent anxiogenic properties in the rat open field test at 10 mg/kg (Šíchová et al. 2025). This bidirectional dose-response is consistent with established CB1 agonist pharmacology. Patients with panic disorder or generalized anxiety disorder may experience symptom exacerbation.

Cannabis use disorder (active), Cannabis use disorder (in remission)

Active or remitted cannabis use disorder is a relative contraindication. HHC shares the CB1-mediated reinforcement mechanism with Δ⁹-THC, and cross-reinforcement is expected. Use may trigger relapse or maintain dependence patterns.

Hepatic impairment, Cirrhosis, Severe liver disease

Hepatic impairment is a relative contraindication. CYP2C9 and CYP3A4 are the expected primary metabolizing enzymes (by class inference from Δ⁹-THC). Compromised hepatic function may prolong HHC exposure and increase risk of adverse effects. No HHC-specific hepatic data exist.

Pregnancy, Lactation

Pregnancy and lactation are absolute contraindications. The endocannabinoid system plays a critical role in neurodevelopment, and exogenous CB1 agonists disrupt this signaling. No HHC-specific teratogenicity data exist, but the risk class is well established for cannabinoids acting at CB1.

Adolescents (under 18), Young adults with ongoing neurodevelopment

Adolescence is a relative contraindication. The endocannabinoid system plays a critical role in neurodevelopment, and CB1 agonism during adolescence is associated with lasting cognitive deficits and altered white matter integrity in the Δ⁹-THC literature. HHC's neurodevelopmental risk profile has not been studied specifically, but the same risk applies by class inference.

Warfarin therapy, Clopidogrel therapy, CYP2C9-metabolized antiepileptics, CYP3A4-metabolized benzodiazepines

Concurrent use of medications metabolized by CYP2C9 or CYP3A4 is a relative contraindication. Δ⁹-THC and CBD inhibit these enzymes; HHC is expected to do the same by class inference. Clinically significant interactions are predicted with warfarin (bleeding risk), clopidogrel (reduced antiplatelet effect), antiepileptics (altered plasma levels), and CYP3A4-metabolized benzodiazepines (prolonged sedation).