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Cannabidiol (CBD) is one of at least 113 active cannabinoids identified in cannabis. It is a major phytocannabinoid, accounting for up to 40% of the plant's extract. CBD is considered to have a wide scope of potential medical applications despite its reputed lack of psychoactivity.

Neurological effects
Cannabidiol has been seen to be an anticonvulsant in animals, but controlled studies in humans are lacking.

Transdermal CBD is neuroprotective in animals.

Dravet syndrome
Dravet syndrome is a rare form of epilepsy that is difficult to treat. It is a catastrophic form of intractable epilepsy that begins in infancy. Initial seizures are most often prolonged events and in the second year of life other seizure types begin to emerge. A number of high profile and anecdotal reports have sparked interest in treatment of Dravet syndrome with CBD. GW Pharmaceuticals is seeking FDA approval to market a formulation of CBD, under the tradename Epidiolex, as a treatment for Dravet syndrome. Epidiolex was granted fast-track status and is in late stage trials following positive early results from the drug. Some cannabis extract preparations containing CBD are marketed as dietary supplements and claim efficacy against Dravet Syndrome. One such preparation is marketed under the tradename Charlotte's web.

Psychotropic effect
A 2014 Cochrane Review concluded that the evidence is insufficient to conclude that CBD has anti-psychotic effects. Others have concluded it may have antipsychotic effects and may counteract the potential psychotomimetic effects of THC on individuals with latent schizophrenia; some reports show it to be an alternative treatment for schizophrenia that is safe and well-tolerated. Studies have shown CBD may reduce schizophrenic symptoms due to its apparent ability to stabilize disrupted or disabled NMDA receptor pathways in the brain, which are shared and sometimes contested by norepinephrine and GABA. Studies have shown cannabidiol decreases activity of the limbic system and decreases social isolation induced by THC in rats. Additionally, a study focusing on the inhibition of cocaine-induced seizures in rats displayed the potential anti-epileptic benefits of CBD.

Chronic cannabidiol administration in rats was found to produce reactions suggesting anxiety, indicating that prolonged treatment with cannabidiol might lead to anxiety. Those results have been contested by Gururajan, and contradict Réus, whose experimentation cover the same duration. The results of one study indicate that the administration of cannabidiol may reduce subjective anxiety in patients diagnosed with SAD.

Research on cannabidiol has shown its efficacy in improving the psychotic symptoms of patients with Schizophrenia by elevating levels of anandamide, an antipsychotic endocannabinoid, in the body. These studies also showed that patients given CBD displayed less adverse side-effects than patients given other antipsychotic drugs. Patients with Huntington's disease reported reduction in chorea severity after taking CBD.

Other research indicates CBD as a possible form of therapy and intervention for those suffering from substance abuse, due to its association with the neural circuits involved in addictive behaviors. CBD has an effect on the 5-HT1A receptor which controls stress responses and compulsive behaviors. Studies in rats show that CBD has in impact on opioid addiction and psychostimulant addiction. There have been studies showing cannabidiol as having a positive impact on cannabis and tobacco addictions in humans.

CBD-enhanced cannabis
Selective breeding by growers in the USA dramatically lowered the CBD content of cannabis; their customers preferred varietals that were more mind-altering due to a higher THC, lower CBD content. This is because cannabidiol's relatively low affinity for the CB1 and CB2 receptors does not produce the effects of intoxication and memory loss commonly experienced by THC users. These individuals are generally less interested in alleviating medical symptoms, and more interested in pursuing the euphoria-inducing effects of cannabis with a higher THC, lower CBD content. However, it is significant to consider the synergistic nature of the two cannabinoids and their ability to enhance one another's therapeutic effects. For example, research suggests CBD may augment the anti-inflammatory benefits of THC. The two molecules in combination have also been reported to more aptly reduce neuropathic pain in users. To meet the demands of medical cannabis patients, growers are currently developing more CBD-rich strains.

Industrial hemp
Several industrial hemp varieties can be legally cultivated in western Europe. A variety such as "Fedora 17" has a cannabinoid profile consistently around 1% cannabidiol (CBD) with THC less than 0.1%.

Extraction can be done with olive oil, ethanol, or CO2, and other nonpolar to semipolar solvents.

Pharmacodynamics
Cannabidiol has a very low affinity for CB1 and CB2 receptors but acts as an indirect antagonist of their agonists. While one would assume that this would cause cannabidiol to reduce the effects of THC, it may potentiate THC's effects by increasing CB1 receptor density or through another CB1-related mechanism. It may also extend the duration of the effects of THC via inhibition of the cytochrome P-450-3A and 2C enzymes.

Recently, it was found to be an antagonist at the putative new cannabinoid receptor, GPR55, a GPCR expressed in the caudate nucleus and putamen. Cannabidiol has also been shown to act as a 5-HT1A receptor partial agonist, an action which may be involved in its antidepressant, anxiolytic, and neuroprotective  effects. Cannabidiol is an allosteric modulator of μ and δ-opioid receptors. Cannabidiol's pharmacological effects have also been attributed to PPAR-γ receptor agonism and intracellular calcium release.

Research suggests that CBD may exert some of its pharmacological action through its inhibition of FAAH, which may in turn increase the levels of endocannabinoids, such as anandamide, produced by the body. Cannabidiol may act as an agonist of VR1, desensitizing it to the action of capsaicin, which partially potentiates CBD as an anti-inflammatory drug.

Pharmacokinetic interactions
There is some preclinical evidence to suggest that cannabidiol may reduce THC clearance, modestly increasing THC's plasma concentrations resulting in a greater amount of THC available to receptors, increasing the effect of THC in a dose-dependent manner. Despite this the available evidence in humans suggests no significant effect of CBD on THC plasma levels.

Pharmaceutical preparations
Nabiximols (USAN, trade name Sativex) is an aerosolized mist for oral administration containing a near 1:1 ratio of CBD and THC. The drug was approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis.

Epidiolex is an oil formulation of CBD extracted from the cannabis plant undergoing clinical trials for refractory epilepsy syndromes.

Isomerism
Based on: Nagaraja, Kodihalli Nanjappa, Synthesis of delta-3-cannabidiol and the derived rigid analogs, Arizona University 1987.

See also: Tetrahydrocannabinol, Abnormal cannabidiol.

Chemistry
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. The synthesis of cannabidiol has been accomplished by several research groups, commonly through the combination of Olivetol and p-mentha-2,8-dien-1-ol in the presence of Boron trifluoride.

Biosynthesis
Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC. An acid-catalyzed reaction between geranylpyrophosphate and olivetolate produces Cannabigerolic acid. In the last step, however, CBD acid synthase is used to yield CBDA rather than THC acid synthase being used to produce THCA.



Legal status
Cannabidiol is not scheduled by the Convention on Psychotropic Substances.

Australia
Prescription Medicine (Schedule 4).

Canada
Cannabidiol is a Schedule II drug in Canada.

United States
Epidiolex, a cannabidiol-containing medication, has received orphan drug status in the United States for treatment of Dravet syndrome, which will allow it to be studied. Though the extraction of CBD from industrial hemp is currently legally permitted throughout the United States, extracting CBD from medical marijuana plants may only be performed in states in which medical marijuana is legal.

Legislation has been passed in several states which allows for the medicinal use of products high in CBD. One piece of such legislation is Carly's Law, passed in Alabama in April of 2014, which permits the prescribed use of cannabidiol for patients with severely-debilitating epilepsy. In Alabama, CBD extracts may not contain plant material and must contain < 3% of THC.

UK
Cannabidiol, in an oral-mucosal spray formulation combined with delta-9-tetrahydrocannabinol, is a prescription product available for relief of severe spasticity due to multiple sclerosis (where other anti-spasmodics have not been effective).

EU
Cannabidiol is listed in EU Cosmetics Ingredient Database.