Overview of CBD: What Is CBD?

Cannabidiol (CBD) is a naturally occurring cannabinoid component of cannabis. It is one of at least 113 cannabinoids identified in hemp plants. While delta-9 tetrahydrocannabinol (THC) is the major active ingredient, cannabidiol (CBD) can make up about 40% of cannabis extracts depending on the plant. CBD has been studied for many different uses (see below). Depending on the species the ratio of THC: CBD will vary. It is widely accepted that marijuana has two main species: Cannabis Indica and Cannabis sativa (3). Generally it was considered that pure sativa has a higher ratio of THC:CBD making it more psychoactive. However crossbreeding of Indica and sativa strains has led to such a wide variety of hybrid strains that making THC:CBD difficult to associate with either Indica or sativa.

As of 2018 in the United States, Food and Drug Administration approval of cannabidiol as a prescription drug called Epidiolex for medical uses has been limited to two rare forms of childhood epilepsy (1).

CBD does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC). It is THC (and not CBD) that is the primary psychoactive component of marijuana.

Chemical and Physical Properties of the Cannabidiol (CBD) Molecule

Cannabidiol is insoluble in water but soluble in organic solvents such as pentane or hexane. 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 (2). The synthesis of cannabidiol has been accomplished by several research groups.(2, 2b)

• Formula: C21H30O2

• Molecular weight: 314.4617

Pharmacological Profile and Mechanism of action - CBD

Although THC and endocannabinoids (produced in the body) activate the CB1 and CB2 receptors (G protein-coupled receptors), CBD does not directly stimulate these receptors. CBD instead displays an unexpectedly high potency as an 'antagonist' of CB1/CB2 receptor in CB1- and CB2-expressing cells, the manner with which it interacts with CB2 receptors providing a possible explanation for its ability to inhibit evoked immune cell migration.(3) Acting as an antagonist for CB1/CB2 suggests that CBD can block some of the psychoactive action of THC (4). However, because of multiple mechanism of CBD there are some circumstances where CBD may actually enhance the effects of the THC (see reference 4).

CBD has a broad pharmacological profile, including interactions with several receptors known to regulate fear and anxiety-related behaviors, specifically the cannabinoid type 1 receptor (CB1R), the serotonin 5-HT1A receptor, and the transient receptor potential (TRP) vanilloid type 1 (TRPV1) receptor. (Ref 5 - review article- see also references 11, 12, 19, 21 within review article). By activating the TRPV-1 receptor, cannabidiol plays a role in the mediation of body temperature, pain perception and inflammation [6]

CBD not only elicits effects within the central nervous system (7), but also within the cardiovascular system. The activation of adenosine receptors by CBD gives the anti-anxiety and anti-inflammatory effects of cannabidiol. Adenosine receptors are also involved in the release of dopamine and glutamate, two neurotransmitters that play major roles inside the body. (8)

GPR55 is another G protein-coupled receptor (like CB1 and CB2) which CBD acts on. CBD is a GPR55 antagonist, as University of Aberdeen scientist Ruth Ross disclosed at the 2010 conference of the International Cannabinoid Research Society in Lund, Sweden. By blocking GPR55 signaling, CBD may act to decrease both bone reabsorption and cancer cell proliferation. By blocking GPR55 signaling, CBD may act to decrease both bone reabsorption and cancer cell proliferation. (9)

Treatment with purified cannabidiol (CBD) appears to counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway similar to effects found with other cannabinoids. (10)

CBD is being studied in a disorder called dystonia. Early research suggests that taking cannabidiol daily for 6 weeks might improve dystonia by 20% to 50% in some people. But higher quality research is needed to confirm this.-- See -Open label evaluation of cannabidiol in dystonic movement disorders.

CBD in combination with Ah 9-delta-tetrahydrocannabinol (THC) been shown to be effective for improving pain, muscle-tightness, and urination frequency in people with MS. (12)

CBD being studied as an antipsychotic "... Results show the ability of CBD to counteract psychotic symptoms and cognitive impairment associated with cannabis use as well as with acute THC administration. In addition, CBD may lower the risk for developing psychosis that is related to cannabis use. These effects are possibly mediated by opposite effects of CBD and THC on brain activity patterns in key regions implicated in the pathophysiology of schizophrenia, such as the striatum, hippocampus and prefrontal cortex. The first small-scale clinical studies with CBD treatment of patients with psychotic symptoms further confirm the potential of CBD as an effective, safe and well-tolerated antipsychotic compound, although large randomized clinical trials will be needed before this novel therapy can be introduced into clinical practice..." read more --A systematic review of the antipsychotic properties of cannabidiol in humans. See also --Cannabis extract helps reset brain function in psychosis-- Summary: "Researchers have found that a single dose of the cannabis extract cannabidiol can help reduce brain function abnormalities seen in people with psychosis. Results provide the first evidence of how cannabidiol acts in the brain to reduce psychotic symptoms."

Cannabidiol normalizes positive symptom-like behaviors in (Amphetamine) kAMPH-sensitized rats-- "The AMPH-sensitization protocol leads to the induction of a permanent hyper-dopaminergic state in limbic regions and is characterized by a behavioral phenotype that is clinically relevant to the positive symptoms of schizophrenia..."

Cannabidiol activates the mTOR signaling cascade..." Importantly, all the prophylactic effects of CBD on schizophrenia-like behaviors in AMPH-sensitized rats were inhibited by co-administration with the mTOR inhibitor, Torin2, and the p70s6k inhibitor, PF4708671. These neuro-molecular findings led to the conclusion that a potential antipsychotic mechanism of action of CBD involves activation of the mTOR signaling cascade..." Read more --A new antipsychotic mechanism of action for cannabidiol --August 8, 2016 by Anand Gururajan.

Pharmacokinetics

The oral bioavailability of CBD is 13 to 19%, while its bioavailability via inhalation is 11 to 45% (mean 31%). The elimination half-life of CBD is 9 hours. see wikipedia

Toxicity

While Cannabidiol (CBD), has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. little is known about its safety and side effect profile in animals and humans.

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