CB1

2021-11-18 links: Endocannabinoid reference:

Cannabinoid Receptor 1 #

Mostly Gi/o.

• Presynaptic CB1 on GABAeric neurons in the VTA, diminishes GABAergic inhibition, leading to increased dopamine release.
• The reason why stimulation doesn’t make you feel high is because there is not a basal cannabinoid tone; Endocannabinoid they are realeased phasically on demand.
• Both high and low activity impairs Memory.
• Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB1 receptor availability
  • As opioidergic tone increases, μ-Opioid Receptor availability is reduced, potentiating Neuropeptide FF production.
  • In morbidly obese subjects, increasing the plasma insulin concentration to supraphysiological levels results in acceleration of central glucose metabolism. Middle-aged subjects with peripheral insulin resistance have blunted glucose metabolism response to insulin also in brain, especially in appetite-controlling regions such as ventral striatum
  • μ stimulates reward associated with food intake.
• Peripheral CB1 receptor blockade acts as a memory enhancer through a noradrenergic mechanism
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• CB1→βγ→AKT→NF-κB→COX-2→PGE2→Glutamate release→NMDA overactivation & downregulation→memory impairment.
  • Acutely, glutamate release→mTOR might lead to memory impairment

5-HT2A #

• Forms heterodimers with 5-HT2A, changing it from Gq to Gi/o.