|Systematic (IUPAC) name|
|Legal status||Schedule I (US) Schedule II (Can)|
|Melt. point||66 °C (151 °F)|
|Boiling point||180 °C (356 °F)
(range: 160–180 °C)
| (what is this?)
Cannabidiol (CBD) is one of at least 85 cannabinoids found in cannabis. It is a major constituent of the plant, second to THC, and represents up to 40% in its extracts. Compared with THC, cannabidiol is non-psychoactive, and is considered to have a wider scope of medical applications than THC, including to epilepsy, multiple sclerosis spasms, anxiety disorders, schizophrenia, nausea, convulsion and inflammation, as well as inhibiting cancer cell growth. CBD may decrease the rate of THC clearance from the body, perhaps by interfering with the metabolism of THC in the liver. Cannabidiol has displayed sedative effects in animal tests. Other research indicates that CBD increases alertness. CBD has been shown to reduce growth of aggressive human breast cancer cells in vitro, and to reduce their invasiveness.
Studies have shown cannabidiol decreases activity of the limbic system and decreases social isolation induced by THC. Cannabidiol has also been shown to reduce anxiety in social anxiety disorder.
Cannabidiol has proven effective in 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%.
In 1985 a single case study suggested that CBD may be effective in the management of levodopa-induced dyskinesia in a Parkinson's Disease patient.
Effects on the brain
A 2010 study found that strains of cannabis containing higher concentrations of cannabidiol did not produce short-term memory impairment vs. strains with similar concentrations of THC, but lower concentrations of CBD. The researchers attributed this attenuation of memory effects to CBD's role as a CB1 antagonist. CBD also appears to protect against 'binge' alcohol induced neurodegeneration.
Recent studies have shown cannabidiol to be as effective as atypical antipsychotics in treating schizophrenia. 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. 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 fewer side effects (extrapyramidal symptoms, increase in prolactin, weight gain) when compared to amisulpride.
A 2008 study published in the British Journal of Psychiatry showed significant differences in the Oxford-Liverpool Inventory of Feelings and Experiences scores between three groups: the first consisted of non-cannabis users, the second consisted of users with THC detected, and the third consisted of users with both THC and CBD detected. The THC-only group scored significantly higher for unusual experiences than the THC-and-CBD group, whereas the THC-and-CBD group had significantly lower introvertive anhedonia scores than the THC-only group and the non-cannabis user group. This research indicates that CBD acts as an anti-psychotic and may counteract the potential psychotomimetic effects of THC on individuals with latent schizophrenia.
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 down-regulates, or "turns off", the activity of ID1, the gene responsible for tumor metastasis in breast and other types of cancers, including the particularly aggressive triple negative breast cancer. The researchers in September 2012 said they hope to start human trials soon.
Cannabidiol has 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."
Non-psychoactive cannabinoids, including cannabidiol (CBD) and other more pronounced CB2 agonists such as cannabinol (CBN, an immunosuppressant), are now seen as promising targets for anti-tumor drugs since they experimentally reduce the size of in-vivo xenografts, for example gliomas. Combinations of submaximal THC doses and CBD have both been successfully applied to greatly increase in-vitro efficacy of temozolomide in glioblastoma multiforme cell lines. CBD likely exerts its effects through the induction of apoptosis by Reactive oxygen species. Non-psychoactive cannabinoids can be administered at much higher doses without the well-known side effects that are sometimes associated with the drop-out rate in trials involving psychoactive cannabinoids.
A team of researchers from the University of California at Irvine proposed in February 2013 that CBD's anti-malignant effect by way of apoptosis may be due to its potential action on "mutant p53 proteins in cancer cells," due to cannabidiol's chemo-physical similarity to stictic acid, a promising anti-cancer compound found in some species of lichens that acts on the aforementioned proteins. The University biologists, chemists and computer scientists "identified an elusive pocket on the surface of the p53 protein that can be targeted by cancer-fighting drugs".
CBD enhanced cannabis
In November 2012, an Israeli medical cannabis facility announced a new strain of the plant which has only cannabidiol as an active ingredient, and virtually no THC, providing some of the medicinal benefits of cannabis without the euphoria. The researchers said the cannabis plant, enriched with CBD, "can be used for treating diseases like rheumatoid arthritis, colitis, liver inflammation, heart disease and diabetes". Research on CBD enhanced cannabis began in 2009, resulting in Avidekel, a cannabis strain that contains 15.8% CBD and less than 1% THC. Raphael Mechoulam, leading cannabinoid researcher, noted "It is possible that (Avidekel's) CBD to THC ratio is the highest among medical marijuana companies in the world, but the industry is not very organised, so one cannot keep exact track of what each company is doing".
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 is also an inverse agonist of CB2 receptors. 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 is an allosteric modulator of μ and δ-opioid receptors. Cannabidiol's pharmacologial effects have also been attributed to PPAR-γ receptor agonism and intracellular calcium release.
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.
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 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.
CBD is in Schedule I in the United States. It is included in the DEA material under "Tetrahydrocannabinols," which is a broad category that encompasses all the phytocannabinoids as analogs of THC. Its DEA # is 7372, and it remains illegal.
Tetrahydrocannabinols, both naturally and synthetically occurring, are currently classified under Schedule I of the US Controlled Substances Act.
Cannabidiol is a Schedule 2 Drug in Canada.
See also↑Jump back a section
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