• Mayuri Vaish

CB1 receptor: more than just to detect cannabinoids

The Cannabinoid CB1 receptor is a part of the endocannabinoid system, and its primary role is to perceive cannabinoids, contributing to feelings of pleasure.[1]

However, evidence has suggested that CB1 receptors may also mediate the differentiation of hematopoietic cells (i.e, stem cells as precursor to blood cells), as well as of murine (mice) embryonic stem cells.[2]

Moreover, they regulate beta-arrestin 1 and 2 levels (responsible for regulating G-coupled-protein receptor, or GCPR, signalling). GCPRs act as secondary messengers that promote internal chemical cell changes in response to detection of an external substance. They also stimulate the activation of the MAPK pathway (similarly, contributes to cell signalling). These signals include altering the permeability of neural ion channels. Specifically, they have suggested to inhibit Calcium channels (thus, inhibiting neural firing), excite Potassium channels (again, inhibiting neural firing), and decrease Chloride ions within the cell (promoting excitation).[3]

They are thus key to maintaining excitation and inhibition of neurons in the brain. This is evident, as increased CB1 activation leads to anxiolytic (anti-anxiety) effects, while lowered CB1 activation has the opposite.[4]

It has also suggested to activate the mTOR pathway, contributing to synaptic plasticity and increased protein synthesis. It has also been linked to increased hippocampal activation (responsible for memory).[5]

More importantly, they have shown to be key to modulating dopaminergic, serotonergic, and cholinergic pathways in the brain - regions linked to the release of dopamine (pleasure), serotonin (pleasure), and acetylcholine (‘fight or flight’) respectively.[6][7][8]

Clearly, they do a lot more than simply detect cannabinoids. However, many of the processes are inextricably linked, and the primary function of CB1 as detectors of cannabinoids still remains the same.