Каннабидиол: Қасиеттері мен зерттелуі

Phytocannabinoid discovered in 1940

Cannabidiol (CBD) (/k//æ//.//n//ə//.//b//ə//./'/d//aɪ//.//əl/) is a phytocannabinoid discovered in 1940. It is one of 113 identified cannabinoids in cannabis plants, along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. CBD is also sold as a herbal dietary supplement promoted with unproven claims of particular therapeutic effects. and can modulate the psychoactive effects of THC on the body if both are present. CBD heated to 250–300 °C may partially be converted into THC. In the United States, the cannabidiol drug Epidiolex was approved by the Food and Drug Administration (FDA) in 2018 for the treatment of two epilepsy disorders.

Cannabidiol is the generic name of the drug and its .

as of 2022, there was little evidence for cannabidiol having a neurological effect in humans. In the United States, federal illegality has made it difficult historically to conduct research on CBD.

In the United States, the FDA has indicated only one brand of prescription cannabidiol called Epidiolex for the treatment of seizures associated with Dravet syndrome, Lennox–Gastaut syndrome, or tuberous sclerosis complex in people one year of age and older. While Epidiolex treatment is generally well tolerated, it is associated with minor adverse effects, such as gastrointestinal upset, decreased appetite, lethargy, sleepiness and poor sleep quality.

Research on other uses for cannabidiol includes several neurological disorders, but the findings have not been confirmed to establish such uses in clinical practice. In October 2019, the FDA issued an advisory warning that the effects of CBD during pregnancy or breastfeeding are unknown, indicating that the safety, doses, interactions with other drugs or foods, and side effects of CBD are not clinically defined, and may pose a risk to the mother and infant. Many claims are made for the therapeutic benefit of cannabidiol that are not backed by sound evidence. Some claims, such as treatment of cancer, are pseudoscience. In 2020, the label for Epidiolex in the US was expanded to include treatment of seizures associated with tuberous sclerosis. Acclaimed for relieving chronic pain, some researchers conclude that the evidence is insufficient to determine the effectiveness of CBD in pain relief, primarily due to the challenging access to pure CBD.

Cannabidiol does not appear to have any intoxicating effects such as those caused by ∆ THC in cannabis, but it is under preliminary research for its possible anti anxiety and anti psychotic effects. Various strains of "medical cannabis" are found to have a significant variation in the ratios of CBD to THC and are known to contain other non psychotropic cannabinoids. Any psychoactive cannabis, regardless of its CBD content, is derived from the flower (or bud) of the genus Cannabis. As defined by US federal law, 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 ∆ tetrahydrocannabinol concentration of no more than 0.3% on a dry weight basis. In the United States, certain standards are required for legal growing, cultivating, and producing the hemp plant, but there are no federal standards for quality being enforced in the hemp industry. Certain state regulations are in place, but vary state to state. For instance, the Colorado Industrial Hemp Program registers growers of industrial hemp and samples crops to verify that the dry weight THC concentration does not exceed 0.3%. Safety studies of cannabidiol showed it is well tolerated, but may cause tiredness, somnolence, sedation, diarrhea, or changes in appetite as common adverse effects with the most common being somnolence and sedation. Side effects of CBD are dose related. Epidiolex documentation lists sleepiness, insomnia and poor quality sleep, decreased appetite, diarrhea, and fatigue. In November 2019, the FDA issued concerns about the safety of cannabidiol, stating that CBD use has potential to cause liver injury, interfere with the mechanisms of prescription drugs, produce gastrointestinal disorders, or affect alertness and mood. acknowledging the unknown effects of protracted use, how it affects the developing brain, fetus or infants during breastfeeding, whether it interacts with dietary supplements or prescription drugs, whether male fertility is affected, and its possible side effects, such as drowsiness. as of September 2019, 1,085 people contacted US poison control centers about CBD induced illnesses, doubling the number of cases over the 2018 rate and increasing by 9 times the case numbers of 2017. Of cases reported in 2019, more than 33% received medical attention and 46 people were admitted to a hospital intensive care unit, possibly due to exposure to other products, or drug interactions with CBD. In vitro, cannabidiol inhibited the activity of voltage dependent sodium and potassium channels, which may affect neural activity. A recent study using X ray crystallography showed that CBD binds inside the sodium channel pore at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition, which could contribute to a reduced excitability. A small clinical trial reported that CBD partially inhibited the CYP2C catalyzed hydroxylation of THC to 11 OH THC. Little is known about potential drug interactions, but CBD mediates a decrease in clobazam metabolism. Work with human liver microsomes shows that cannabidiol inhibits CYP3A5 and CYP3A4 to some degree.

The number of research projects and scientific publications on cannabidiol and other cannabinoids in pets surged in the late 2010s; nonetheless, as of December 2020, there were no hemp derived, cannabinoid rich registered veterinary medicinal products in any of the major regions (see #Legal status). In the US and other territories there are, however, numerous veterinary nutraceutical products available over the counter (OTC). The lack of clarity in the regulations governing veterinary hemp food supplements allows for products of questionable quality to flood the market, which may pose a risk to the wellbeing of pets and owners. To understand better the benefits of CBD and associated compounds for the quality of life of animals, companies specialized in CBD products for animals have been funding research projects.

CBD's ability to help regulate the endocannabinoid system and reduce the release of excitatory neurotransmitters could result in a retrograde inhibitory signal that lessens chronic pain responses. Studies in dogs with chronic pain associated with osteoarthritis showed an increase in level of activity in animals receiving CBD rich food supplements. it could be expected that CBD based products would be helpful to manage seizures in dogs. However, despite the numerous case reports presented by veterinary neurologists supporting the benefits of CBD as adjunctive therapy, as of December 2020, published controlled studies have not shown a statistically significant decrease in the number of seizures across the groups receiving CBD. A 24 hour kinetic examination in dogs showed that the absorption of the cannabidiolic acid (CBDA) does occur, and that this molecule is absorbed least twice as well as CBD post oral ingestion. It was found that the major metabolites of CBD in humans (7 OH CBD and 7 COOH CBD) are not prevalent in dogs, while 6 OH CBD was found to be the primary metabolite in dogs receiving a CBD enriched cannabis derived herbal extract, suggesting that canine and human CBD metabolic route might be somewhat different. The anticonvulsant effects provided by cannabidiol (Epidiolex) in people with certain forms of epilepsy do not appear to involve cannabinoid receptors. Cannabidiol may be an antagonist of GPR55, a G protein coupled receptor and putative cannabinoid receptor shown by in vitro studies to be widely distributed in the brain. Cannabidiol may interact with various neurotransmitters, such as serotonin, dopamine, and GABA.

The oral bioavailability of cannabidiol is approximately 6% in humans, while its bioavailability via inhalation is 11 to 45% (mean 31%). In New Zealand, Sativex is "approved for use as an add on treatment for symptom improvement in people with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti spasticity medication." Epidiolex (Epidyolex in Europe) is an orally administered cannabidiol solution. In strongly basic media and the presence of air, it is oxidized to Cannabinodiol (CBND) and a quinone called HU 331. Under acidic conditions it cyclizes to THC, which also occurs during pyrolysis, and during smoking. The synthesis of cannabidiol has been accomplished by several research groups.

Cannabis produces CBD through the same metabolic pathway as THC, until the next to last step, where CBDA synthase performs catalysis instead of THCA synthase.

In the typical operating temperature range of e cigarettes , 25–52% of CBD is transformed into other chemical substances: Δ9 THC, Δ8 THC, cannabinol and cannabichromene as predominant pyrolysates. From a chemical point of view, CBD in e cigarettes can be considered as a precursor of THC. For example, a 2017 analysis of cannabidiol content in oil, tincture, or liquid vape products purchased online in the United States showed that 69% were mislabeled, with 43% having higher and 26% having lower content than stated on product labels. In 2020, the FDA conducted a study of 147 CBD products and found that half contained THC. From 2015 to November 2022, the FDA issued dozens of warning letters to American manufacturers of CBD products for false advertising and illegal interstate marketing of CBD as an unapproved drug to treat diseases, such as cancer, osteoarthritis, symptoms of opioid withdrawal, Alzheimer's disease, and pet disorders. Chemical analysis of CBD products found that many did not contain the levels of CBD claimed in advertising. The warning also applied to hemp CBD capsules and oil that were being marketed illegally while not adhering to the federal definition of a dietary supplement. and Egyptian Cannabis indica resin. The chemical formula of CBD was proposed from a method for isolating it from wild hemp.

Selective breeding of cannabis plants has expanded and diversified as commercial and therapeutic markets develop. Some growers in the US succeeded in lowering the proportion of CBD to THC to accommodate customers who preferred varietals that were more mind altering due to the higher THC and lower CBD content. In the US, hemp is classified by the federal government as cannabis containing no more than 0.3% THC by dry weight. This classification was established in the 2018 Farm Bill and was refined to include hemp sourced extracts, cannabinoids, and derivatives in the definition of hemp.

Food and beverage products containing cannabidiol were widely marketed in the United States as early as 2017. Hemp seed ingredients which do not naturally contain THC or CBD (but which may be contaminated with trace amounts on the outside during harvesting) were declared by the US Food and Drug Administration as generally recognized as safe (GRAS) in December 2018. CBD itself has not been declared GRAS, and under US federal law is illegal to sell as a food, dietary supplement, or animal feed. Similar to energy drinks and protein bars which may contain vitamin or herbal additives, food and beverage items can be infused with CBD as an alternative means of ingesting the substance. Some companies marketing CBD infused food products with claims that are similar to the effects of prescription drugs have received warning letters from the FDA for making unsubstantiated health claims. In February 2019, the New York City Department of Health announced plans to fine restaurants that sell food or drinks containing CBD, beginning in October 2019.

Cannabidiol has been used by professional and amateur athletes across disciplines and countries, with the World Anti Doping Agency removing CBD from its banned substances list. The United States Anti Doping Agency and United Kingdom Anti Doping Agency do not have anti CBD policies, with the latter stating that, "CBD is not currently listed on the World Anti Doping Agency Prohibited List. As a result, it is permitted to use in sport, though the intended benefits are unclear and not backed by clinical evidence. All other cannabinoids (including but not limited to cannabis, hashish, marijuana, and THC) are prohibited in competition. The intention of the regulations is to prohibit cannabinoids that activate the same receptors in the brain as activated by THC." In 2019, the cannabis manufacturer Canopy Growth acquired majority ownership of BioSteel Sports Nutrition, which is developing CBD products under endorsement by numerous professional athletes. The National Hockey League Alumni Association began a project with Canopy Growth to determine if CBD or other cannabis products might improve neurological symptoms and quality of life in head injured players. Numerous professional athletes use CBD, primarily for treating pain.

Prescription medicine (Schedule 4) for therapeutic use containing two percent (2.0%) or less of other cannabinoids commonly found in cannabis (such as ∆ THC). A Schedule 4 drug under the SUSMP is a 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. In June 2020, the Australian Therapeutic Goods Administration (TGA) published a consultation on a proposal to pave the way to make "low dose" CBD available to consumer/patients via pharmacists only through moving products from Schedule 4 to 3. Any products sold would need to have their safety, quality and efficacy pre assessed by the TGA and be formally approved for sale (details to be outlined by TGA). They would be made available to over 18s only, with the maximum daily dose of 60mg/day, up to 2% THC finished product allowed, 30 day maximum supply, plant derived or synthetic. This proposal is based on an initial literature review on the safety of low dose CBD published by the TGA in April 2020. Epidyolex was approved for the adjunctive therapy of seizures associated with Lennox–Gastaut syndrome or with Dravet syndrome in September 2020. However, there exists a legal gap because of the lack of a legally permissible minimum amount of THC in the products containing cannabinoids.

In October 2018, cannabidiol became legal for recreational and medical use by the federal Cannabis Act. as of 2019, CBD products in Canada could only be sold by authorized retailers or federally licensed medical companies, limiting their access to the general public. Nonetheless, with online delivery services and over 2,600 authorized cannabis retail stores as of October 2021, accessibility has steadily increased over time. The Canadian government states that CBD products "are subject to all of the rules and requirements that apply to cannabis under the Cannabis Act and its regulations."

As of May 2023, the State Agricultural and Food Inspection of the Czech Republic is putting together broad regulations regarding a ban on CBD products. They will make it illegal to sell products containing cannabidiol and other cannabinoids derived from hemp, as a result of EU Novel Food Regulation. In case of Czech Republic, European Industrial Hemp Association has submitted an official request to the Czech Republic to recognize natural hemp extracts with cannabinoids as traditional food.

In 2019, the European Commission announced that CBD and other cannabinoids would be classified as "novel foods", meaning that CBD products would require authorization under the EU Novel Food Regulation stating that because "this product was not used as a food or food ingredient before May 15, 1997, before it may be placed on the market in the EU as a food or food ingredient, a safety assessment under the Novel Food Regulation is required." The recommendation – applying to CBD extracts, synthesized CBD, and all CBD products, including CBD oil – was scheduled for a final ruling by the European Commission in March 2019. 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 or is approved for such use.

In 2022, the HKSAR Government proposed a ban on any use of cannabidiol (including for academic research and by medical professionals) within the Hong Kong territory, making Hong Kong the first jurisdiction in the world to have complete prohibition of cannabidiol, starting from February 1, 2023, in part due to the possible presence of THC which is illegal in Hong Kong, according to a research subsidized by the Hong Kong SAR Government.

In 2017, the New Zealand government made changes to the regulations so that restrictions would be removed, which meant a doctor was able to prescribe cannabidiol to patients. The passing of the Misuse of Drugs (Medicinal Cannabis) Amendment Act in December 2018 means cannabidiol is no longer a controlled drug in New Zealand, but is a prescription medicine under the Medicines Act, with the restriction that "the tetrahydrocannabinols (THCs) and specified substances within the product must not exceed 2 percent of the total CBD, tetrahydrocannabinol (THC) and other specified substances."

According to a document received in response to an appeal to the Ministry of Internal Affairs of the Russian Federation, measures of state control in the Russian Federation regarding CBD have not been established. However, there is also a response from the Ministry of Health of the Russian Federation indicating that CBD can be considered as an isomer of restricted THC. The "isomer" argument is nonetheless vague, as progesterone, which is freely sold in pharmacies, is also an isomer of THC, all three being On February 17, 2020, the deputy of the Moscow City Duma Darya Besedina sent an official request to the Prime Minister of the Russian Federation Mikhail Mishustin with a request to eliminate that legal ambiguity by publishing official explanations and, if necessary, making required changes in the corresponding government decree.

Singapore allows medical cannabis on a case by case basis, usually as a last resort drug. Each case is evaluated by the government, and largely comes in the form of Cannabidiol. However, the country is flexible to what is required for patient treatment, despite having some of the strictest drug laws in the world.

Cannabidiol is classified as a medical product in Sweden. However, in July 2019, Supreme Court of Sweden ruled that CBD oil with any concentration of THC falls under the narcotic control laws.

While THC remains illegal, cannabidiol is not subject to the Swiss Narcotic Acts because it does not produce a comparable psychoactive effect. Cannabis products containing less than 1% THC can be sold and purchased legally.

On 7 April 2021 the Ukrainian government legalised use of isolated cannabidiol. Additionally, it approved Nabiximols, a cannabidiol containing drug, for medical use.

Cannabidiol, in an oral mucosal spray formulation combined with delta 9 tetrahydrocannabinol, is a product available by prescription for the relief of severe spasticity due to multiple sclerosis (where other anti spasmodics have not been effective) in the United Kingdom. Until 2017, products containing cannabidiol marketed for medical purposes were classed as medicines by the UK regulatory body, the Medicines and Healthcare products Regulatory Agency (MHRA), and could not be marketed without regulatory approval for the medical claims. as of 2018, cannabis oil is legal to possess, buy, and sell in the UK, providing the product does not contain more than 1 milligram of THC and is not advertised as providing a medicinal benefit. Individual police officers and others who are ill informed of the exact legislature pertaining to cannabidiol, however, may erroneously consider it of dubious legality, reflecting lack of awareness. In January 2019, the UK Food Standards Agency indicated it would regard CBD products, including CBD oil, as a novel food having no history of use before May 1997, and stated that such products must have authorisation and proven safety before being marketed. The deadline for companies with existing products to submit a full and validated novel foods application with the FSA was 31 March 2021; failure to do so before this date would exclude those companies from selling CBD. New products containing CBD after this deadline would require a fully approved application. In February 2020, the UK FSA advised vulnerable people, such as pregnant women, breastfeeding mothers, and those already taking medication for other medical concerns not to take CBD. The FSA further recommended that healthy adults should not consume more than 70mg CBD per day.

as of 2023, cannabidiol extracted from marijuana remains a Schedule I Controlled Substance, and is not approved as a prescription drug or dietary supplement or allowed for interstate commerce in the United States. CBD derived from hemp (with 0.3% THC or lower) is legal to sell as a cosmetics ingredient or for other purposes not regulated by the FDA, but cannot be sold under federal law as an ingredient in food, dietary supplement, or animal feed. It is a common misconception that the legal ability to sell hemp (which may contain CBD), and hemp extracts and derivatives (including CBD), makes CBD legal for sale as a supplement or medicine. In September 2018, the GW Pharmaceuticals drug Epidiolex was placed in Schedule V of the Controlled Substances Act by the Drug Enforcement Administration (DEA), following its approval by the FDA for rare types of childhood epilepsy. Epidiolex is available for prescription use in all 50 states. In 2013, a CNN program that featured Charlotte's Web cannabis brought increased attention to the use of CBD for the treatment of seizure disorders in children. A number of states passed laws over the next few years to allow the use of low THC, high CBD cannabis oil in such situations. These states were in addition to the states that had already legalized cannabis for medical or recreational use. The 2014 Farm Bill legalized the sale of "non viable hemp material" grown within states participating in the Hemp Pilot Program which defined hemp as cannabis containing less than 0.3% of THC. The 2018 Farm Bill removed the hemp plant and all "derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta 9 tetrahydrocannabinol concentration of not more than 0.3 percent on a dry weight basis," including CBD, from the Controlled Substances Act, making them legal to manufacture in the United States. The FDA retains regulatory authority over hemp derived CBD, The 2018 Farm Bill requires that research and development of CBD for a therapeutic purpose would have to be conducted under notification and reporting to the FDA.