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Cannabidiol (CBD) 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. , clinical research on CBD included studies related to anxiety,
cognition Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...
, movement disorders, and pain, but there is insufficient high-quality evidence that cannabidiol is effective for these conditions. Nevertheless, CBD is an herbal
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
promoted with unproven claims of particular therapeutic effects. The global market size for CBD was predicted to exceed billion by 2028. Cannabidiol can be taken internally in multiple ways, including by
inhaling Breathing (or ventilation) is the process of moving air into and from the lungs to facilitate gas exchange with the internal environment, mostly to flush out carbon dioxide and bring in oxygen. All aerobic creatures need oxygen for cellular ...
cannabis smoke or vapor, oral, and as an aerosol spray into the cheek. It may be supplied as CBD oil containing only CBD as the active ingredient (excluding tetrahydrocannabinol HCor terpenes), CBD-dominant
hemp Hemp, or industrial hemp, is a botanical class of ''Cannabis sativa'' cultivars grown specifically for industrial or medicinal use. It can be used to make a wide range of products. Along with bamboo, hemp is among the fastest growing plants o ...
extract An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures, absolutes or in powder form. The aromatic principles of many spices, nuts, h ...
oil, capsules, dried cannabis, or prescription liquid
solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Soluti ...
. CBD does not have the same
psychoactivity A psychoactive drug, psychopharmaceutical, psychoactive agent or psychotropic drug is a chemical substance, that changes functions of the nervous system, and results in alterations in perception, mood, consciousness, cognition or behavior. Th ...
as THC, and can negate the psychoactive effects of THC on the body if both are present. However, in 2022 it was discovered that CBD heated to 250-300 °C (typically in e-cigarettes) may partially be converted into THC. , the mechanism of action for its biological effects had not been determined. Unlike THC, which acts on the cannabinoid receptor type 1 (CB1) as a partial agonist, CBD instead is a negative
allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a Receptor (biochemistry), receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allos ...
of CB1 receptors. In the United States, the cannabidiol drug Epidiolex was approved by the Food and Drug Administration in 2018 for the treatment of two epilepsy disorders. While the
2018 United States Farm Bill The 2018 farm bill or Agriculture Improvement Act of 2018 is an enacted United States farm bill that reauthorized $867 billion for many expenditures approved in the prior farm bill (the Agricultural Act of 2014). The bill was passed by the Senat ...
removed hemp and hemp extracts (including CBD) from the
Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...
, the marketing and sale of CBD formulations for medical use or as an ingredient in dietary supplements or manufactured foods remains illegal under FDA regulation, .


Medical uses

''Cannabidiol'' is the generic name of the drug and its .


Research

, there was limited high-quality evidence for cannabidiol having a neurological effect in humans.


Epilepsy

In the United States, the FDA has
indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
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. In the European Union, cannabidiol (Epidyolex) is indicated for use as adjunctive therapy of seizures associated with Lennox Gastaut syndrome (LGS) or Dravet syndrome (DS), in conjunction with
clobazam Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselec ...
, for people two years of age and older. In 2020, the label for Epidiolex in the US was expanded to include seizures associated with tuberous sclerosis complex. Epidiolex/Epidyolex is the first prescription formulation of plant-derived cannabidiol approved by regulatory bodies in the US and Europe.


Other uses

Research on other uses for cannabidiol includes several
neurological Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...
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 Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination ...
.


Non-intoxicating effects

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 Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...
effects. As the legal landscape and understanding about the differences in medical cannabinoids unfolds, experts are working to distinguish "medical cannabis" (with varying degrees of psychotropic effects and deficits in executive function) from "medical CBD therapies", which would commonly present as having a reduced or non-psychoactive side-effect profile. 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. 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%.


Side effects

Research indicates that cannabidiol may reduce adverse effects of THC, particularly those causing intoxication and
sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...
, but only at high doses. 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.


Potential interactions

Laboratory evidence indicated that cannabidiol may reduce THC clearance, increasing plasma concentrations which may raise THC availability to receptors and enhance its effect in a dose-dependent manner. 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 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various com ...
-catalyzed
hydroxylation In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH groups in a ...
of THC to
11-OH-THC 11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC, alternatively numbered as 7-OH-Δ1-THC), usually referred to as 11-hydroxy-THC, is the main active metabolite of tetrahydrocannabinol (THC), which is formed in the body after THC is consumed. A ...
. Little is known about potential drug interactions, but CBD mediates a decrease in
clobazam Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselec ...
metabolism.


Veterinary medicine


Research

The number of research projects and scientific publications on cannabidiol and other cannabinoids in pets surged in the late 2010s; nonetheless, , 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.


Canine osteoarthritis

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.


Epilepsy

From the results seen in humans with drugs such as Epidiolex and Sativex in scientific studies and reviews, 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, , published controlled studies have not shown a statistically significant decrease in the number of seizures across the groups receiving CBD. Further research in this area is required before any clear conclusion can be drawn.


Pharmacokinetics

The oral bioavailability of CBD varies greatly across species and it is linked to the presentation and the time of administration. 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 7-Hydroxycannabidiol (7-OH-CBD) is an active metabolite of cannabidiol, generated in the body from cannabidiol by the action of the enzyme CYP2C19. While methods have been developed for its synthetic production, and measurement of levels in the b ...
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.


Pharmacology


Pharmacodynamics

Cannabidiol has low
affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...
for the cannabinoid CB and CB receptors, although it acts as an antagonist of CB/CB agonists, despite this low affinity. The core effect of antagonism of CB receptors is reduced binding affinity of THC and any of its related isomers. Cannabidiol may be 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 also may act as an
inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...
of
GPR3 G-protein coupled receptor 3 is a protein that in humans is encoded by the ''GPR3'' gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction. GPR ...
,
GPR6 G protein-coupled receptor 6, also known as GPR6, is a protein which in humans is encoded by the ''GPR6'' gene. Function GPR6 is a member of the G protein-coupled receptor family of transmembrane receptors. It has been reported that GPR6 is b ...
, and
GPR12 Probable G-protein coupled receptor 12 is a protein that in humans is encoded by the ''GPR12'' gene. The gene product of GPR12 is an orphan receptor, meaning that its endogenous ligand is currently unknown. Gene disruption of GPR12 in mice result ...
. CBD has been shown to act as a
serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
5-HT receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neur ...
partial agonist. At higher concentrations, CBD acts as an
inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...
of 5-HT receptors. It is an
allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a Receptor (biochemistry), receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allos ...
of the μ- and
δ-opioid receptor The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous ligan ...
s as well. The pharmacological effects of CBD may involve PPARγ
agonism Agonism (from Greek ἀγών '' agon'', "struggle") is a political and social theory that emphasizes the potentially positive aspects of certain forms of conflict. It accepts a permanent place for such conflict in the political sphere, but seeks ...
, inhibition of voltage-gated cation channels, and intracellular calcium release.


Pharmacokinetics

The oral bioavailability of cannabidiol is approximately 6% in humans, while its bioavailability via
inhalation Inhalation (or Inspiration) happens when air or other gases enter the lungs. Inhalation of air Inhalation of air, as part of the cycle of breathing, is a vital process for all human life. The process is autonomic (though there are exceptions ...
is 11 to 45% (mean 31%). The elimination half-life of CBD is 18–32 hours. Cannabidiol is
metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
in the liver as well as in the
intestine The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
s by the
cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzymes
CYP2B6 Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances. Funct ...
, CYP2C19, CYP2D6, CYP2J2, and
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
, and by the isoenzymes
UGT1A7 UDP glucuronosyltransferase 1 family, polypeptide A7 is a protein that in humans is encoded by the ''UGT1A7'' gene. This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecu ...
, UGT1A9, and UGT2B7, forming a variety of metabolites such as 7-hydroxycannabidiol as well as the 6α- and 6β-hydroxy isomers and derivatives hydroxylated on the alkyl side chain, followed by glucuronidation.
CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...
facilitates decarbonylation of CBD to liberate carbon monoxide, a bioactive gasotransmitter and pharmaceutical candidate. CBD may have a wide margin in dosing.


Pharmaceutical preparations

Nabiximols (brand name Sativex), an oromucosal spray made of a complex botanical mixture containing cannabidiol (CBD), delta-9-tetrahydrocannabinol (THC), and additional cannabinoid and non-cannabinoid constituents from cannabis sativa plants, was approved by Health Canada in 2005, to treat central neuropathic pain in
multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
, and in 2007, for cancer-related pain. 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 is an orally administered cannabidiol solution. It was approved in 2018, by the US Food and Drug Administration (FDA) for treatment of two rare forms of childhood epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, and seizures associated with tuberous sclerosis complex. In the US, it is approved in these indications for patients one year of age and older.


Chemistry

At room temperature, cannabidiol is a colorless crystalline solid. In strongly basic media and the presence of air, it is oxidized to a
quinone The quinones are a class of organic compounds that are formally "derived from aromatic compounds
uch as benzene or naphthalene Uch ( pa, ; ur, ), frequently referred to as Uch Sharīf ( pa, ; ur, ; ''"Noble Uch"''), is a historic city in the southern part of Pakistan's Punjab province. Uch may have been founded as Alexandria on the Indus, a town founded by Alexand ...
by conversion of an even number of –CH= groups into –C(=O)– groups with any necessary rearrangement of double ...
. Under acidic conditions it cyclizes to THC, which also occurs during pyrolysis, but not during combustion (smoking). The synthesis of cannabidiol has been accomplished by several research groups.


Biosynthesis

'' Cannabis'' produces CBD-
carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
through the same metabolic pathway as THC, until the next to last step, where
CBDA synthase Cannabidiolic acid synthase (, ''CBDA synthase'') is an enzyme with systematic name ''cannabigerolate:oxygen oxidoreductase (cyclizing, cannabidiolate-forming)''. It is an oxidoreductase found in ''Cannabis sativa'' that catalyses the formation ...
performs catalysis instead of
THCA synthase Tetrahydrocannabinolic acid (THCA) synthase (full name ''Δ1-tetrahydrocannabinolic acid synthase'') is an enzyme responsible for catalyzing the formation of THCA from cannabigerolic acid (CBGA). THCA is the direct precursor of tetrahydrocann ...
.


Isomerism


Pyrolysis

In the typical operating temperature range of e-cigarettes (), 25–52% of CBD is transformed into other chemical substances: Δ9-THC, Δ8-THC,
cannabinol Cannabinol (CBN) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS). CBN w ...
and
cannabichromene Cannabichromene (CBC), also called cannabichrome, cannanbichromene, pentylcannabichromene or cannabinochromene, is an anti-inflammatory which may contribute to the pain-killing effect of cannabis. It is one of the hundreds of cannabinoids found i ...
as predominant pyrolysates. From a chemical point of view, CBD in e-cigarettes can be considered as a precursor of THC.


History

Efforts to isolate the active ingredients in cannabis were made in the 19th century. Cannabidiol was studied in 1940 from Minnesota wild hemp and Egyptian ''Cannabis indica'' resin. The chemical formula of CBD was proposed from a method for isolating it from wild hemp. Its structure and
stereochemistry Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...
were determined in 1963.


Plant breeding

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.


Society and culture


Foods and beverages

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 (FDA) 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. State laws vary considerably as non-medical cannabis and derived products have been legalized in some jurisdictions in the 2010s. The global market size for CBD was predicted to exceed billion by 2028. Similar to energy drinks and
protein bars Protein bars are nutrition bars that contain a high proportion of protein to carbohydrates/ fats. Dietary purpose Protein bars are targeted to people who primarily want a convenient source of protein that does not require preparation (unless h ...
which may contain vitamin or herbal additives, food and beverage items can be infused with CBD as an alternative means of ingesting the substance. In the United States, numerous products are marketed as containing CBD, but in reality contain little or none. Some companies marketing CBD-infused food products with claims that are similar to the effects of
prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
s have received warning letters from the Food and Drug Administration for making unsubstantiated
health claim A health claim on a food label and in food marketing is a claim by a manufacturer of food products that their food will reduce the risk of developing a disease or condition. For example, it is claimed by the manufacturers of oat cereals that oat ...
s. In February 2019, the New York City Department of Health announced plans to
fine Fine may refer to: Characters * Sylvia Fine (''The Nanny''), Fran's mother on ''The Nanny'' * Officer Fine, a character in ''Tales from the Crypt'', played by Vincent Spano Legal terms * Fine (penalty), money to be paid as punishment for an offe ...
restaurants that sell food or drinks containing CBD, beginning in October 2019.


Sports

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 The United States Anti-Doping Agency (USADA, ) is a non-profit, non-governmental 501(c)(3) organization and the national anti- doping organization (NADO) for the United States. To protect clean competition and the integrity of sport and prevent ...
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.


Legal status


Australia

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 The Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) is an Australian Statutory instrument, legislative instrument produced by the Therapeutic Goods Administration (TGA)., subsection 4A. Before 2010, it was known as the ''St ...
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.


Bulgaria

In 2020, Bulgaria became the first country in the European Union to allow retail sales of food products and supplements containing CBD, despite the ongoing discussion within the EU about the classification of CBD as a novel food. However, there exists a legal gap because of the lack of a legally-permissible minimum amount of THC in the products containing cannabinoids.


Canada

In October 2018, cannabidiol became legal for recreational and medical use by the federal ''
Cannabis Act The ''Cannabis Act'' (also known as Bill C-45) is a law which legalized recreational cannabis use in Canada in combination with its companion legislation Bill C-46, ''An Act to Amend the Criminal Code''. The law is a milestone in the legal hi ...
''. , 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 , 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." It requires "a processing licence to manufacture products containing CBD for sale, no matter what the source of the CBD is, and that CBD and products containing CBD, such as cannabis oil, may only be sold by an authorized retailer or licensed seller of medical CBD." Edible CBD products were scheduled to be permitted for sale in Canada on October 17, 2019, for human consumption. , it was still illegal to carry cannabis and cannabis-derived products (including products containing CBD) across the Canadian border. If one carries any amount of cannabis for any purpose (including medical), it needs to be declared to the
Canada Border Services Agency The Canada Border Services Agency (CBSA; french: Agence des services frontaliers du Canada, ''ASFC'') is a federal law enforcement agency that is responsible for border control (i.e. protection and surveillance), immigration enforcement, and cu ...
. Not declaring it is a serious criminal offence.


European Union

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. If approved, manufacturers of CBD products would be required to conduct safety tests and prove safe consumption, indicating that CBD products would not be eligible for legal commerce until at least 2021. In December 2020, the European Commission concluded that CBD should not be considered as drug and can be qualified as food. 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. Several industrial hemp varieties can be legally cultivated in Western Europe. A variety such as "Fedora 17" has a cannabinoid profile consistently around 1%, with THC less than 0.3%.


Hong Kong

In 2022, the
HKSAR Government The Government of the Hong Kong Special Administrative Region, commonly known as the Hong Kong Government or HKSAR Government, refers to the executive authorities of Hong Kong SAR. It was formed on 1 July 1997 in accordance with the Sino-Br ...
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.


New Zealand

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 The Misuse of Drugs (Medicinal Cannabis) Amendment Act 2018 (2018 No 54) is an Act of Parliament in New Zealand which amends the Misuse of Drugs Act 1975 to allow terminally-ill people to consume cannabis and to possess a cannabis utensil. The ...
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."


Russian Federation

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 In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...
" argument is nonetheless vague, as
progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
, 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 Darya Stanislavovna Besedina (russian: Да́рья Станисла́вовна Бесе́дина; born 22 July 1988) is a Russian politician. She's a deputy of the Moscow City Duma. Biography She was born in Khimki, Moscow Oblast, RSFSR. ...
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

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.


Sweden

Cannabidiol is classified as a medical product in Sweden. However, in July 2019,
Supreme Court of Sweden The Supreme Court of Sweden ( sv, Högsta domstolen, abbreviated ''HD'') is the supreme court and the third and final instance in all civil and criminal cases in Sweden. Before a case can be decided by the Supreme Court, leave to appeal mu ...
ruled that CBD oil with any concentration of THC falls under the narcotic control laws.


Switzerland

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.


Ukraine

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


United Kingdom

Cannabidiol, in an oral-mucosal spray formulation combined with
delta-9-tetrahydrocannabinol Tetrahydrocannabinol (THC) is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C21H30O2) describes multiple isomers, the term ''THC'' ...
, 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 A regulatory agency (regulatory body, regulator) or independent agency (independent regulatory agency) is a government authority that is responsible for exercising autonomous dominion over some area of human activity in a licensing and regulatin ...
, the
Medicines and Healthcare products Regulatory Agency The Medicines and Healthcare products Regulatory Agency (MHRA) is an executive agency of the Department of Health and Social Care in the United Kingdom which is responsible for ensuring that medicines and medical devices work and are acceptably ...
(MHRA), and could not be marketed without regulatory approval for the medical claims. , 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. 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.


United Nations

Cannabidiol is scheduled under the Single Convention on Narcotic Drugs as cannabis. International Narcotics Control Board reminds Member States that, at the reconvened sixty-third session of the Commission on Narcotic Drugs, in December 2020, the States members of the Commission rejected the recommendation of WHO that a footnote be added to the entry for cannabis and cannabis resin in Schedule I of the 1961 Convention as amended to exempt from international control preparations containing predominantly CBD and not more than 0.2 per cent of delta-9-THC.


United States

, cannabidiol extracted from marijuana remains a Schedule I Controlled Substance, and is not approved as a
prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
or
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
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, following its approval by the FDA for rare types of childhood epilepsy, the GW Pharmaceuticals drug Epidiolex was rescheduled (by the Drug Enforcement Administration) as a Schedule V drug to allow for its prescription use. Epidiolex still requires rescheduling in some states before it can be prescribed in those states. In 2013, a CNN program that featured Charlotte's web cannabis brought increased attention to the use of CBD in the treatment of seizure disorders. Since then, 16 states have passed laws to allow the use of CBD products with a physician's recommendation (instead of a prescription) for treatment of certain medical conditions. This is in addition to the 30 states that have passed comprehensive medical cannabis laws, which allow for the use of cannabis products with no restrictions on THC content. Of these 30 states, eight have legalized the use and sale of cannabis products without requirement for a physician's recommendation. , CBD was not an FDA-approved drug eligible for interstate commerce, and the FDA encouraged manufacturers to follow procedures for
drug approval An approved drug is a medicinal preparation that has been validated for a therapeutic use by a ruling authority of a government. This process is usually specific by country, unless specified otherwise. Process by country United States In the ...
. Federal illegality has made it difficult historically to conduct research on CBD. Cannabidiol is currently the subject of an FDA investigational new drug evaluation, and is not considered legal as a
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
or food ingredient, . CBD is openly sold in head shops and
health food store A health food store (or health food shop) is a type of grocery store that primarily sells health foods, organic foods, local produce, and often nutritional supplements. Health food stores typically offer a wider or more specialized selection of fo ...
s in some states where such sales have not been explicitly legalized. State and local governments may also regulate cannabidiol. For example, the Massachusetts Department of Agricultural Resources issued a rule in June 2019 aligning state CBD regulations with FDA regulations. This means that although recreational marijuana is legal in the state, CBD cannot legally be sold in food or as a dietary supplement under state law.


Health concerns

In November 2019, the FDA issued concerns about the safety of cannabidiol, stating that CBD use has potential to cause
liver injury A liver injury, also known as liver laceration, is some form of trauma sustained to the liver. This can occur through either a blunt force such as a car accident, or a penetrating foreign object such as a knife. Liver injuries constitute 5% of a ...
, interfere with the mechanisms of
prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
s, produce gastrointestinal disorders, or affect alertness and mood. In October 2020, the FDA updated its safety concerns about CBD, acknowledging the unknown effects of protracted use, how it affects the developing brain, fetus or infants during breastfeeding, whether it interacts with
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
s or
prescription drug A prescription drug (also prescription medication or prescription medicine) is a pharmaceutical drug that legally requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription. The rea ...
s, whether male fertility is affected, and its possible side effects, such as drowsiness.


Mislabeling and poisoning

Studies conducted by the FDA from 2014 through 2019 have determined that a majority of CBD products are not accurately labeled with the amount of CBD they contain. For example, a 2017 analysis of cannabidiol content in oil, tincture, or liquid
vape An electronic cigarette is an electronic device that simulates tobacco smoking. It consists of an Atomizer nozzle, atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of tobacco smoke, smoke, ...
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 label A label (as distinct from signage) is a piece of paper, plastic film, cloth, metal, or other material affixed to a container or product, on which is written or printed information or symbols about the product or item. Information printed dir ...
s. In 2020, the FDA conducted a study of 147 CBD products and found that half contained THC. , 1,085 people contacted US
poison control center A poison control center is a medical service that is able to provide immediate, free, and expert treatment advice and assistance over the telephone in case of exposure to poisonous or hazardous substances. Poison control centers answer questions ...
s 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.


2018 Farm Bill and hemp

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 United States Farm Bill The 2018 farm bill or Agriculture Improvement Act of 2018 is an enacted United States farm bill that reauthorized $867 billion for many expenditures approved in the prior farm bill (the Agricultural Act of 2014). The bill was passed by the Senat ...
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 The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...
, making them legal to manufacture in the United States. The FDA retains regulatory authority over hemp-derived CBD, while the
DEA The Drug Enforcement Administration (DEA; ) is a United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within the U.S. It is the lead agency for domestic enf ...
is not involved in the regulation of legally-compliant hemp and hemp products. 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. In the United States, hemp-derived CBD is legal to sell for industrial purposes or as a cosmetics ingredient, but under FDA regulation it cannot be marketed for medical use or as an ingredient in food, dietary supplements, or animal feed.


FDA warning letters

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 A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
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. In 2022, the FDA stated that "scientific studies show possible harm to the male reproductive system, including testicular atrophy, harm to the liver, and interactions with certain medications. The FDA has not found adequate information showing how much CBD can be consumed, and for how long, before causing harm. This is particularly true for vulnerable populations like children and those who are pregnant." In December 2020, the
Federal Trade Commission The Federal Trade Commission (FTC) is an independent agency of the United States government whose principal mission is the enforcement of civil (non-criminal) antitrust law and the promotion of consumer protection. The FTC shares jurisdiction ov ...
initiated a law enforcement crackdown on American companies marketing CBD products as unapproved drugs. 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 A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
.


See also

* Hash oil *
Hemp oil Hemp oil (hemp seed oil) is oil obtained by pressing hemp seeds. Cold pressed, unrefined hemp oil is dark to clear light green in color, with a nutty flavor. The darker the color, the grassier the flavour. It should not be confused with hash oi ...
* List of investigational antipsychotics * List of investigational analgesics


References


Further reading

* *


External links

* {{Portal bar , Medicine 5-HT1A agonists Analgesics Anti-inflammatory agents Anticonvulsants Phytocannabinoids Cyclohexenes CYP2D6 inhibitors CYP3A4 inhibitors Endocannabinoid reuptake inhibitors Natural phenols 2,6-Dihydroxybiphenyls Orphan drugs