Cannabidiol (INN; abbreviated as: CBD) is one of at least 113 cannabinoids identified in cannabis. It is a major phytocannabinoid, accounting for up to 40% of the plant's extract. CBD does not appear to have any psychoactive effects such as those caused by tetrahydrocannabinol (THC). It may have a downregulating impact on disordered thinking and anxiety. Potential uses are the subject of ongoing research.
Cannabidiol use appears to be safe, but a 2017 review recommended larger and longer human trials before a definitive conclusion is reached. One animal study reported that co-administration with THC potentiated the effects of THC. One possible mechanism is by competing for the THC receptor sites.
Video Cannabidiol
Uses
Pain associated with multiple sclerosis
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.
Research
Addiction treatment
Two systematic review on CBD and addiction reported beneficial effects for alleviating tobacco and cannabis dependence. The anti-addictive properties displayed might be due to CBD's protective effect on stress and neurotoxicity. Both reviews recommended more research.
Anti-inflammatory
Two reviews address research on the theory that CBD alone or in combination with THC may have anti-oxidant and anti-inflammatory activity. Neither cited any human trials.
Epilepsy
Anecdotal reports and early studies suggested that CBD may be of value in treating epilepsy, but the quality of the studies was too poor to draw definitive conclusions. A 2014 Cochrane review included four randomized controlled trials, but all were of poor quality. A double-blinded, randomized, placebo-controlled study of CBD oil on treating Dravet syndrome, a rare form of epilepsy that begins in infancy and is difficult to treat, was conducted in 2017 and found that CBD oil significantly reduced the number of seizures with a dosing of 20mg/kg. However, it also caused increased diarrhea, vomiting, fevers, fatigue, abnormal liver function tests (LFTs), and somnolence. The LFTs showed elevated ALT and AST up to three times of normal, but only in the patients also taking valproate. The study already suggests that this might be an interaction of valproate and CBD. The abnormal LFT normalized during the trial in the patients who kept taking CBD.
GW Pharmaceuticals is seeking FDA approval to market a liquid formulation of pure plant-derived CBD, under the trade name Epidiolex (containing 99% cannabidiol and less than 0.10% ?9-THC) as a treatment for Dravet syndrome. Epidiolex was granted fast-track status and orphan drug status in the United States for treatment of Dravet syndrome in July 2015.
Maps Cannabidiol
Adverse effects
CBD safety in humans has been studied in several small studies, suggesting that it is well tolerated. The most common side effects were tiredness, diarrhea and decreased appetite. The authors recommended more clinical trials with safety evaluations.
Interactions
There is 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.
Pharmacology
Pharmacodynamics
Cannabidiol has very low affinity for the cannabinoid CB1 and CB2 receptors but acts as an indirect antagonist of these receptors. It may potentiate THC's effects by increasing CB1 receptor density or through another CB1 receptor-related mechanism. Cannabidiol may also extend the duration of the effects of THC via inhibition of the cytochrome P450, CYP3A and CYP2C enzymes.
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 shown to act as a 5-HT1A receptor partial agonist, and this action may be involved in the antidepressant, anxiolytic, and neuroprotective effects of cannabidiol. It is an allosteric modulator of the ?- and ?-opioid receptors as well. Cannabidiol's pharmacological effects have additionally been attributed to PPAR? agonism and intracellular calcium release.
Research suggests that CBD may exert some of its pharmacological action through its inhibition of fatty acid amide hydrolase (FAAH), which may in turn increase the levels of endocannabinoids, such as anandamide, produced by the body. It has also been speculated that some of the metabolites of CBD have pharmacological effects that contribute to the biological activity of CBD.
Recently, cannabidiol has been identified as a novel inverse agonist of the GPR12.
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.
Biosynthesis
Cannabis produces CBD-carboxylic acid through the same metabolic pathway as THC, until the next to last step, where CBDA synthase performs catalysis instead of THCA synthase.
Isomerism
Based on: Nagaraja, Kodihalli Nanjappa, Synthesis of delta-3-cannabidiol and the derived rigid analogs, Arizona University 1987.
See also: Tetrahydrocannabinol#Isomerism, Abnormal cannabidiol.
Society and culture
Food and beverage
Similar to recreational marijuana, food and beverage items can be infused with CBD as an alternative means of ingesting the substance. In the United States, a number of products are marketed as containing CBD, but in reality contain little or none.
CBD-infused food is increasingly becoming commonplace in the United States, as natural grocers are now picking up food and beverage products with CBD in them. However, some companies marketing CBD-infused food products with claims that are similar to the effects of prescription drugs have received warning letters from the Food and Drug Administration for making unsubstantiated claims.
Natural sources
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 and lower CBD content. To meet the demands of medical cannabis patients, growers are currently developing more CBD-dominant strains.
Legal status
CBD does not appear to have any psychoactive ("high") effects such as those caused by ?9-THC in marijuana, but may have anti-anxiety and anti-psychotic effects. As the legal landscape and understanding about the differences in medical cannabinoids unfolds, it will be increasingly important to distinguish "medical marijuana" (with noted varying degrees of psychotropic effects and deficits in executive function) - from "medical CBD".
Various breeds/strains of "medical marijuana" are found to have a significant variety in the ratios of CBD-to-THC and are known to contain other non-psychotropic cannabinoids. However it is only the amount of ?9-THC that chemically gives a legal determination as to whether the plant material(s) used for the purposes of extracting CBD are considered hemp, or considered marijuana.
Any psychoactive marijuana, regardless of its CBD content, is derived from the flower (or bud) of the genus Cannabis. Non-psychoactive hemp (also commonly-termed industrial hemp), regardless of its CBD content, is any part of the cannabis plant, whether growing or not, containing a ?-9 tetrahydrocannabinol concentration of no more than three-tenths of one percent (0.3%) on a dry weight basis. Certain standards are required for the legal growth and production of hemp. The Colorado Industrial Hemp Program registers growers of industrial hemp and samples crops to verify that the THC concentration does not exceed 0.3% on dry weight basis.
United Nations
Cannabidiol is not scheduled by the Convention on Psychotropic Substances.
United States
In the United States, cannabidiol is a Schedule I drug under the Controlled Substances Act. This means that production, distribution and possession of CBD is illegal under federal law. In 2016, the Drug Enforcement Administration added "marijuana extracts" to the list of Schedule I drugs, which it defined as "an extract containing one or more cannabinoids that has been derived from any plant of the genus Cannabis, other than the separated resin (whether crude or purified) obtained from the plant." Previously, CBD had simply been considered "marijuana", which is also a Schedule I drug.
A CNN program that featured Charlotte's Web cannabis in 2013 brought increased attention to the use of CBD in the treatment of seizure disorders. Since then, 30 states have passed laws to allow for the use of CBD products (not exceeding a specified concentration of THC) for the treatment of certain medical conditions. This is in addition to the 29 states that have passed comprehensive medical cannabis laws, which allow for the use of cannabis products with no restrictions on THC content. Of these 29 states, eight have legalized the use and sale of cannabis products without requirement for a doctor's recommendation.
Although most states restrict the use of CBD products to certain medical conditions, manufacturers of CBD claim their products are derived from industrial hemp, and therefore legal for anyone to use. A number of these manufacturers ship CBD products to all 50 states, which the federal government has so far not intervened in. CBD is also openly sold in head shops and health food stores in some states where such sales have not been explicitly legalized.
Australia
Prescription medicine (Schedule 4) for therapeutic use containing 2 per cent (2.0%) or less of other cannabinoids commonly found in cannabis (such as ?9-THC). A schedule 4 drug under the SUSMP is Prescription Only Medicine, or Prescription Animal Remedy - Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription.
New Zealand
Cannabidiol is currently a class B1 controlled drug in New Zealand under the Misuse of Drugs Act. It is also a prescription medicine under the Medicines Act. In 2017 the rules were changed so that anyone wanting to use it could go to the Health Ministry for approval. Prior to this, the only way to obtain a prescription was to seek the personal approval of the Minister of Health.
Associate Health Minister Peter Dunne said restrictions would be removed, which means a doctor will now be able to prescribe cannabidiol to patients.
Canada
Cannabidiol is a Schedule II drug in Canada. As such, it is only available with a prescription. It is available as a spray, called Sativex produced by GW Pharmaceuticals in the UK, for use in multiple sclerosis. The Canadian Government has started the process to pass its recreational legalization bill, which was planned to come in to effect on July 1, 2018, but at this time no set date has been announced. When announced it will erase the necessity to obtain prescriptions for commercial CBD, as well as provision of cannabis federally to its citizens for recreational use.
Europe
Cannabidiol is listed in the EU Cosmetics Ingredient Database (CosIng). However, the listing of an ingredient, assigned with an INCI name, in CosIng does not mean it is to be used in cosmetic products nor approved for such use.
Cannabidiol is listed in the EU Novel Food Catalogue. This listing only applies to isolated or synthetic CBD, not to crude hemp extracts or tinctures naturally containing CBD.
The European Industrial Hemp Association has issued a position paper suggesting regulatory framework in EU.
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%.
Although the World Health Organization listed Cannabidiolum in a list of International Nonproprietary Names for Pharmaceutical Substances (INN) on 30 June 2016. French and Spanish versions wrongly mention agonist action of CBD on cannabinoid receptors while the English version says CBD is a cannabinoid receptor antagonist.
Sweden
CBD is not classified in Sweden.
Sativex (CBD and THC) is a prescription product available for relief of severe spasticity due to multiple sclerosis.
United Kingdom
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).
As of 31 December 2016, products containing cannabidiol that are marketed for medical purposes are classed as medicines by the UK regulatory body, the Medicines and Healthcare products Regulatory Agency (MHRA) and cannot be marketed without regulatory approval for the medical claims.
Switzerland
While THC remains illegal, CBD is not subject to the Swiss Narcotic Acts because this substance does not produce a comparable psychoactive effect. Cannabis products containing less than 1% THC can be sold and purchased legally.
See also
- List of investigational antipsychotics
- List of investigational analgesics
References
Source of the article : Wikipedia
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