Cannabis has been used for millennia and there is a substantial body of anecdotal evidence related to its psychoactive and therapeutic effects.
Cannabinoids are active molecules unique to the cannabis plant, and remain the only molecules clinically approved for the pharmacological modulation of the endocannabinoid system.
Distinction between "Indica" and "Sativa" is related to botanical features of the cannabis subspecies rather than to differences in pharmacological or psychoactive profiles.
Although the cannabis plant may contain hundreds of molecules, its pharmacological effect is determined by the relative abundance of THC and CBD, which defines its chemotype.
The Endocannabinoid System
The Endocannabinoid System is a lipid signaling system that modulates many physiological processes in the whole organism favoring homeostasis. Its key components include:
• Type-1 and type-2 cannabinoid (CB1 and CB2) receptors:
Cannabinoid recptors are G protein-coupled receptors that mediate several intracellular processes such as the closure of calcium channels and the inhibition of adenylate cyclase. CB1 receptors are predominantly expressed in the nervous and musculoskeletal system, the gastrointestinal tract and adipose tissue. CB2 is primarily expressed in cells of the immune system, including the glia.
The endogenous ligands of CB1 and CB2 are lipid messengers
derived from arachidonic acid called “endocannabinoids”,
namely N-arachidonoyl ethanolamide (“anandamide”)
and 2-arachidonoylglycerol (2-AG). Δ9-tetrahydrocannabinol
(THC), the main active component of cannabis,
mimics the action of anandamide and 2-AG by acting
as a partial agonist of both CB1 and CB2. Central activation
of CB1 receptors by THC is responsible for the classical
psychoactivity associated to cannabis consumption.
CBD does not activate CB1 or CB2 receptors and, therefore, does not cause euphoria and is generally well tolerated. However, it may modulate the therapeutical profile of THC, improving its tolerability and safety. Inhalation of CBD may help with the symptomatic alleviation of different clinical conditions such as chronic headache and migraine, chronic pelvic pain, inflammatory bowel diseases, stress and anxiety disorders, and substance use disorder (as a harm reduction
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