CB1mediated

CB1mediated refers to effects and signaling that occur via the cannabinoid receptor type 1 (CB1). CB1 is a G protein-coupled receptor highly enriched in the central nervous system, especially in the hippocampus, basal ganglia, cerebellum, and cortex, with additional expression in some peripheral tissues. Activation of CB1 initiates intracellular cascades that modulate neuronal activity and synaptic transmission.

CB1 signaling typically couples to Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP. This can lead to the opening of certain potassium channels and the closure of voltage-gated calcium channels, which decreases neurotransmitter release at presynaptic terminals. Across many synapses, CB1 acts as a retrograde signal from the postsynaptic neuron to presynaptic terminals, dampening neurotransmission and shaping synaptic plasticity.

Endocannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) are produced on demand and serve as endogenous ligands for CB1. They are broken down by enzymes such as FAAH and MAGL, respectively. Endocannabinoid signaling underlies phenomena like depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE).

Physiological roles attributed to CB1-mediated signaling include analgesia, appetite and energy balance, mood and stress response, learning and memory, and motor control. Exogenous cannabinoids, notably delta-9-tetrahydrocannabinol (THC), exert CB1-mediated effects such as euphoria, sedation, and perceptual changes. Pharmacological manipulation of CB1—agonists, antagonists, or inverse agonists—has been explored for pain, obesity, and addiction, but clinical use has been tempered by adverse effects and abuse potential.

Research into CB1-mediated signaling continues to illuminate its contributions to neurophysiology and pathology, including potential neuroprotective roles and implications for psychiatric disorders. Understanding CB1-mediated mechanisms remains essential for interpreting endocannabinoid function and for the therapeutic development of cannabinoid-based interventions.