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Cannabinoid receptor type 1 (CB1) and Cannabinoid receptor type 2 (CB2) (CB1, CB2)

Target
CB1, CB2
Molecular classification
G protein-coupled receptor (GPCR), Receptor
01

Overview

Cannabinoid pathways refer to the network of signaling mediated by the endogenous cannabinoids, their biosynthetic and degradative enzymes, and especially the cannabinoid receptors type 1 and type 2. Both are G protein-coupled receptors: CB1 is highly expressed in the central nervous system (especially in the brain), mediating most of the psychotropic effects of cannabis, as well as roles in pain, memory, neuroprotection, and metabolism. CB2 is mostly found on immune cells and peripheral tissues, involved in regulation of inflammation and immune responses. Both receptors can be activated by endogenous ligands (anandamide, 2-AG), plant-derived cannabinoids (THC, CBD), and synthetic drugs. They have broad physiological and pathological relevance but are challenging drug targets due to overlapping ligand specificities, tissue distributions, and potential safety liabilities. The term "cannabinoid pathways" is imprecise and should be replaced by the specific receptors CB1 and CB2 for structured information extraction.

Other names
Central cannabinoid receptorCNR1Peripheral cannabinoid receptorCNR2Endocannabinoid receptor
02

Mechanism of action

Agonism (THC, WIN 55212-2 act as agonists at CB1 and CB2); Antagonism/inverse agonism (rimonabant is a CB1 antagonist/inverse agonist); Modulation of Gi/o protein-coupled signaling (inhibition of adenylate cyclase, regulation of ion channels, MAPK pathway); Modulation of neurotransmitter release (suppression of GABA, glutamate); Immunomodulation

03

Biological functions

Signal transductionRetrograde neurotransmissionRegulation of neurotransmitter releaseModulation of painInflammationImmune responseNeuroprotectionRegulation of appetite and metabolism
04

Disease associations

Neurodegenerative diseaseInflammationPainEpilepsyObesityPsychiatric disorders (including depression, anxiety, schizophrenia)Cancer
05

Safety considerations

CNS side effects (CB1 agonists: psychotropic effects, cognitive impairment, sedation)Potential for dependence/abuse (CB1 agonists, e.g., THC)Psychiatric effects (depression, anxiety, psychosis—especially with CB1 antagonists like rimonabant)Immunosuppression (CB2 modulation)Off-target or unpredictable systemic effects
06

Interacting drugs

Δ9-Tetrahydrocannabinol (THC)

7 more in the full profile.

07

Biomarkers

CB1 and CB2 receptor expression levels in tissues of interest (pet imaging)Circulating endocannabinoids (e.g., anandamide, 2-AG)Not well-established clinical biomarkers for patient selection

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