Tolerance
A reduction in response to a drug following repeated exposure, requiring higher doses to achieve the same effect. THC produces tolerance primarily through CB1 receptor downregulation.
In Depth
THC tolerance develops rapidly with regular use, primarily through CB1 receptor internalization and downregulation in the brain. PET imaging studies show CB1 receptor density decreases by 15–20% in heavy cannabis users compared to non-users. Tolerance reverses within 2–4 weeks of abstinence. CBD does not appear to produce significant tolerance. Tolerance to THC's psychoactive effects develops faster than tolerance to its analgesic effects, which has implications for medical cannabis dosing.
Related Terms
Further Reading
More in Pharmacology
Endocannabinoid System (ECS)
A lipid-based retrograde neurotransmitter system comprising endogenous cannabinoids (endocannabinoids), their receptors (CB1, CB2), and metabolic enzymes.
CB1 Receptor
Cannabinoid receptor type 1. A G protein-coupled receptor (GPCR) primarily expressed in the central nervous system. The primary target of THC's psychoactive effects.
CB2 Receptor
Cannabinoid receptor type 2. A GPCR primarily expressed in immune tissues and peripheral organs. Less abundant in the CNS than CB1.
Anandamide (AEA)
N-arachidonoylethanolamine. The first endocannabinoid identified. A partial agonist at CB1 and CB2 receptors, named from the Sanskrit word "ananda" meaning bliss.
2-Arachidonoylglycerol (2-AG)
The most abundant endocannabinoid in the brain. A full agonist at both CB1 and CB2 receptors.