Cannabinoid therapy is connected to the part of the biological matrix where body and brain meet. Since CBD (cannabidiol) and other compounds in cannabis are so similar to the chemicals created by our own bodies, they are integrated better than many synthetic drugs. According to Bradley E. Alger, a leading scientist in the study of endocannabinoids with a PhD from Harvard in experimental psychology, “With complex actions in our immune system, nervous system, and virtually all of the body’s organs, the endocannabinoids are literally a bridge between body and mind. By understanding this system, we begin to see a mechanism that could connect brain activity and states of physical health and disease.”
Anxiolytic effects of CBD in models of generalized anxiety have been linked to specific receptor mechanisms and brain regions. The midbrain dorsal periaqueductal gray (DPAG) is integral to anxiety, orchestrating autonomic and behavioral responses to threat , and DPAG stimulation in humans produces feelings of intense distress and dread . Microinjection of CBD into the DPAG produced anxiolytic effects in the EPM, VGC, and ETM that were partially mediated by activation of 5-HT1ARs but not by CB1Rs [65, 68]. The bed nucleus of the stria terminalis (BNST) serves as a principal output structure of the amygdaloid complex to coordinate sustained fear responses, relevant to anxiety . Anxiolytic effects of CBD in the EPM and VCT occurred upon microinjection into the BNST, where they depended on 5-HT1AR activation , and also upon microinjection into the central nucleus of the amygdala . In the prelimbic cortex, which drives expression of fear responses via connections with the amygdala , CBD had more complex effects: in unstressed rats, CBD was anxiogenic in the EPM, partially via 5-HT1AR receptor activation; however, following acute restraint stress, CBD was anxiolytic . Finally, the anxiolytic effects of systemic CBD partially depended on GABAA receptor activation in the EPM model but not in the VCT model [61, 62].
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 ). 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 . 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 . 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].
Cannabidiol is insoluble in water but soluble in organic solvents such as pentane. At room temperature, it is a colorless crystalline solid. In strongly basic media and the presence of air, it is oxidized to a quinone. Under acidic conditions it cyclizes to THC, which also occurs during pyrolysis (smoking). The synthesis of cannabidiol has been accomplished by several research groups.
Laboratory evidence indicated that cannabidiol may reduce THC clearance, increasing plasma concentrations which may raise THC availability to receptors and enhance its effect in a dose-dependent manner. In vitro, cannabidiol inhibited receptors affecting the activity of voltage-dependent sodium and potassium channels, which may affect neural activity. A small clinical trial reported that CBD partially inhibited the CYP2C-catalyzed hydroxylation of THC to 11-OH-THC.
Oral CBD products with a ratio of 20:1 or higher and administered as drops, capsules, or edibles can be very effective in treating pain, especially the inflammatory type. Most discussions of treating pain with CBD suggest that finding the right dosage is critical. Always start with the micro dose to test sensitivity and go up as needed within the dosing range by body weight until symptoms subside. The micro to standard dose is usually recommended to treat pain, but patients need to carefully monitor their condition and experiment to find the right formula; 10–40 mg of CBD or CBD+THC together is usually enough.
Cannabidiol has been found to act as an antagonist of GPR55, a G protein-coupled receptor and putative cannabinoid receptor that is expressed in the caudate nucleus and putamen in the brain. It has also been found to act as an inverse agonist of GPR3, GPR6, and GPR12. Although currently classified as orphan receptors, these receptors are most closely related phylogenetically to the cannabinoid receptors. In addition to orphan receptors, CBD has been shown to act as a serotonin 5-HT1A receptor partial agonist, and this action may be involved in its antidepressant, anxiolytic, and neuroprotective effects. It is an allosteric modulator of the μ- and δ-opioid receptors as well. The pharmacological effects of CBD have additionally been attributed to PPARγ agonism and intracellular calcium release.
Buying online is less reliable still because there’s no regulation or standardization. What you see on the label may not be what you are getting. A 2017 study in JAMA found that of the 84 CBD products researchers bought online, 43% had more CBD than indicated, while 26% had less, and some had unexpected THC. “There’s a 75% chance of getting a product where the CBD is mislabeled,” says Marcu, one of the study’s coauthors.
The National Cancer Institute details several studies into the anti-tumor effects of CBD. One study in mice and rats suggest CBDs “may have a protective effect against the development of certain types of tumors.” CBDs may do this by inducing tumor cell death, inhibiting cancer cell growth, and by controlling and inhibiting the spread of cancer cells.
Would I say that CBD oil has fundamentally changed my life? No. But per the Charlotte's Web website, this is the typical first experience. "Anyone who has ever started a new vitamin or supplement routine knows the short answer to how long it takes to kick in is—'it depends,'" reads the article on what to expect from hemp oil. "For many newcomers, they're not sure what to imagine, or some anticipate a huge change right away. For most of us, though, dietary supplements take time."