[22] The CB1 receptor is a pre-synaptic heteroreceptor that modulates neurotransmitter release when activated in a dose-dependent, stereoselective and pertussis toxin-sensitive manner.

[19] The CB1 receptor is activated by cannabinoids, generated naturally inside the body (endocannabinoids) or exogenously, normally through cannabis or a related synthetic compound.

[24] In terms of function, the inhibition of intracellular cAMP expression shortens the duration of pre-synaptic action potentials by prolonging the rectifying potassium A-type currents, which is normally inactivated upon phosphorylation by PKA.

[31] Acting as a neuromodulator, the CB1 receptor inhibits the release of both excitatory and inhibitory neurotransmitters including acetylcholine, glutamate, GABA, noradrenaline, 5-HT, dopamine, D-aspartate, and cholecystokinin.

[17] The inverse agonist MK-9470 makes it possible to produce in vivo images of the distribution of CB1 receptors in the human brain with positron emission tomography.

[24]CB1 receptors are expressed most densely in the central nervous system and are largely responsible for mediating the effects of cannabinoid binding in the brain.

[31] CB1 mRNA transcripts are abundant in GABAergic interneurons of the hippocampus, indirectly reflecting the expression of these receptors and elucidating the established effect of cannabinoids on memory.

Cannabinoids also likely play an important role in the development of memory through their neonatal promotion of myelin formation, and thus the individual segregation of axons.

Consistent with the variable expression of both excitatory glutamate and inhibitory GABA interneurons in both the basal ganglia's direct and indirect motor loops, synthetic cannabinoids are known to influence this system in a dose-dependent triphasic pattern.

Decreased locomotor activity is seen at both higher and lower concentrations of applied cannabinoids, whereas an enhancement of movement may occur upon moderate dosages.

[20] However, these dose-dependent effects have been studied predominately in rodents, and the physiological basis for this triphasic pattern warrants future research in humans.

[33] Many of the documented analgesic effects of cannabinoids are based on the interaction of these compounds with CB1 receptors on spinal cord interneurons in the superficial levels of the dorsal horn, known for its role in nociceptive processing.

[34] In the visual system, cannabinoids agonist induce a dose dependent modulation of calcium, chloride and potassium channels.

[35] The activation of CB1 in the human body generally inhibits neurotransmitter release, controls pain, regulates metabolism, and monitors the cardiovascular system.

[36] CB1 receptors are implicated in a number of physiological processes related to the central nervous system (CNS) including brain development, learning and memory, motor behavior, regulation of appetite, body temperature, pain perception, and inflammation.

CB1 receptors localized in GABAergic neurons can modulate food intake, learning and memory processes, drug addiction, and related behaviors.

CB1 receptors localized in glutamatergic neurons are capable of mediating olfactory processes, neuroprotection, social behaviors, anxiety, and fear memories.

Improvements from use of CB agonist in MS are associated with the activation of CB1 and CB2 receptors, leading to dual anti-inflammatory and neuroprotective effects throughout the CNS.

[37] In several brain regions, including the dorsolateral prefrontal cortex (DLPFC) and hippocampus, dysregulation of the CB1 receptor is implicated in the development of schizophrenia.

Abnormal functioning of the CB1 receptor compromises intricate neural systems that are responsible for controlling cognition and memory, which contributes to the pathology.