Following cloning of the endogenous receptor for THC, namely the CB1R, endogenous CB1R ligands, or “endocannabinoids” (eCBs) were discovered, namely anandamide (AEA) and 2-arachidonoylglycerol (reviewed in [22]). The CB1R is an inhibitory Gi/o protein-coupled receptor that is mainly localized to nerve terminals, and is expressed on both γ-aminobutryic acid-ergic and glutamatergic neurons. eCBs are fatty acid derivatives that are synthesized on demand in response to neuronal depolarization and Ca2+ influx, via cleavage of membrane phospholipids. The primary mechanism by which eCBs regulate synaptic function is retrograde signaling, wherein eCBs produced by depolarization of the postsynaptic neuron activate presynaptic CB1Rs, leading to inhibition of neurotransmitter release [23]. The “eCB system” includes AEA and 2-arachidonoylglycerol; their respective degradative enzymes fatty acid amide hydroxylase (FAAH) and monoacylglycerol lipase; the CB1R and related CB2 receptor (the latter expressed mainly in the periphery); as well as several other receptors activated by eCBs, including the TRPV1 receptor, peroxisome proliferator-activated receptor-γ, and G protein-coupled 55 receptor, which functionally interact with CB1R signaling (reviewed in [21, 24]). Interactions with the TRPV1 receptor, in particular, appear to be critical in regulating the extent to which eCB release leads to inhibition or facilitation of presynaptic neurotransmitter release [25]. The TRPV1 receptor is a postsynaptic cation channel that underlies sensation of noxious heat in the periphery, with capsacin (hot chili) as an exogenous ligand. TRPV1 receptors are also expressed in the brain, including the amygdala, periaqueductal grey, hippocampus, and other areas [26, 27].
The 44,000-square-foot building hulks across from a police station in an industrial part of Denver, along a gritty stretch of converted warehouses that’s come to be known as the Green Mile. There’s nothing to indicate the nature of the enterprise. The door buzzes open, and I’m met by the chief horticulturist of Mindful, one of the largest cannabis companies in the world. A druidlike 38-year-old with keen blue eyes, Phillip Hague wears fatigues, hiking boots, and the incredulous grin of someone who—through a confluence of events he never imagined possible—has found his exact life’s calling.
Bioavailability: The bioavailability of orally-administered CBD is considered extremely low (around 6%). If you smoke cannabidiol, the bioavailability increases to over 30% and if you utilize an intranasal preparation, bioavailability may reach nearly 50%.  However, since many people are using oral preparations of CBD, the bioavailability is low and will require a high dose.
THC is the primary psychoactive compound in marijuana and it is what people are searching for when they want a product that gives them a "high." Unlike THC, CBD isn't known to cause psychoactive effects, and is therefore attractive to those who want to avoid the high but who believe there are other benefits of CBD, said Sara Ward, a pharmacologist at Temple University in Philadelphia. [Healing Herb? Marijuana Could Treat These 5 Conditions]

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