Cannabidiol

Cannabidiol (CBD) is a cannabinoid found in Cannabis. It is a major constituent of the plant, representing up to 40% in its extracts.

It has displayed sedative effects in animal tests. Some research, however, indicates that CBD can increase alertness. It may decrease the rate of THC clearance from the body, perhaps by interfering with the metabolism of THC in the liver.

Medically, it has been shown to relieve convulsion, inflammation, anxiety, and nausea, as well as inhibit cancer cell growth. Recent studies have shown cannabidiol to be as effective as atypical antipsychotics in treating schizophrenia. Studies have also shown that it may relieve symptoms of dystonia.

In November 2007, it was reported that CBD reduces growth of aggressive human breast cancer cells in vitro and reduces their invasiveness.

A 2008 study published in the British Journal of Psychiatry showed significant differences in Oxford-Liverpool Inventory of Feelings and Experiences scores between three groups: The first consisted of non-cannabis users, the second consisted of users with Δ9-THC detected, and the third consisted of users with both Δ9-THC and CBD detected. The Δ9-THC only group scored significantly higher for unusual experiences than the Δ9-THC and CBD group, whereas the Δ9-THC and CBD group had significantly lower introvertive anhedonia scores than the Δ9-THC only group and non-cannabis user group. This research indicates that CBD acts as an anti-psychotic and may counteract the potential effects of THC on individuals with latent schizophrenia.

Medicinal use
Cannabidiol is shown to decrease activity of the limbic system and to decrease social isolation induced by THC. It's also shown that Cannabidiol reduces anxiety in social anxiety disorder. In April 2005, Canadian authorities approved the marketing of Sativex, a mouth spray for multiple sclerosis to alleviate pain. Sativex contains tetrahydrocannabinol together with cannabidiol. It is marketed in Canada by GW Pharmaceuticals.

Studies have shown that CBD may reduce schizophrenic symptoms in patients, likely due to their apparent ability to stabilize disrupted or disabled NMDA receptor pathways in the brain, which are shared and sometimes contested by norepinephrine and GABA. Leweke et al. performed a double blind, 4 week, explorative controlled clinical trial to compare the effects of purified cannabidiol and the atypical antipsychotic amisulpride on improving the symptoms of schizophrenia in 42 patients with acute paranoid schizophrenia. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by Brief Psychiatric Rating Scale and Positive and Negative Syndrome Scale. While there was no statistical difference between the two treatment groups, cannabidiol induced significantly less side effects (extrapyramidal symptoms, increase in prolactin, weight gain) when compared to amisulpride.

Cannabidiol has also been shown as being effective treating an often drug-induced set of neurological movement disorders known as dystonia. In one study, five out of five participants showed noted improvement in their dystonic symptoms by 20-50%. CBD also appears to protect against 'binge' alcohol induced neurodegeneration.

Pharmacology
Cannabidiol has no affinity for CB1 and CB2 receptors but acts as an indirect antagonist of cannabinoid agonists. 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 agonist, an action which is involved in its antidepressant, anxiolytic, and neuroprotective  effects.

Cannabidiol has also been shown to inhibit cancer cell growth with low potency in non-cancer cells. Although the inhibitory mechanism is not yet fully understood, Ligresti et al. suggest that "cannabidiol exerts its effects on these cells through a combination of mechanisms that include either direct or indirect activation of CB2 and TRPV1 receptors, and induction of oxidative stress, all contributing to induce apoptosis." In November 2007, researchers at the California Pacific Medical Center reported that CBD shows promise for controlling the spread of metastatic breast cancer. In vitro CBD downregulates the activity of the gene ID1 which is responsible for tumor metastasis.

Chemistry
Cannabidiol is insoluble in water but soluble in organic solvents. At room temperature it is a colorless crystalline solid. In strongly basic medium 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.

Biosynthesis
Cannabis, produces CBD-carboxylic acid through the same metabolic pathway as THC, until the last step, where CBDA synthase performs catalysis instead of THCA synthase.

Legal Status
In Canada Cannabidiol is a Schedule 2 Drug, a category that encompasses quantities of cannabis less than 30 grams, and various related synthetic derivatives and preparations. In the United States it is unscheduled. Only cannabis (the plant itself) and the tetrahydrocannabinol cannabinoids are listed in DEA Drug Scheduling.