Dependence

In clinical pharmacology, dependence denotes a state of neuroadaptation in which abrupt cessation of a drug produces a characteristic withdrawal syndrome. Cannabis dependence reflects homeostatic downregulation and desensitization of CB1 receptors following chronic THC exposure, demonstrated in vivo by PET imaging (Hirvonen et al. 2012, Molecular Psychiatry; D'Souza et al. 2016, Biological Psychiatry: CNNI). Physiological dependence (tolerance + withdrawal) is distinct from the behavioral syndrome of compulsive drug-seeking, though the two frequently coexist. Contemporary nomenclature (DSM-5-TR; NIDA) deliberately separates "dependence" — which can occur with legitimate therapeutic use of many agents — from "addiction" or "substance use disorder," which require impaired control and continued use despite harm. ICD-11 retains a "cannabis dependence" category within its disorders due to substance use. NASEM 2017 found substantial evidence linking frequent cannabis use to development of problem-use syndromes. → See also: Tolerance, Withdrawal, CUD, Addiction.