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Cannabidiol has been studied since the mid-18th century7. It was isolated for the first time in 1940 by Roger Adams from ethanol extract of hemp (Minnesota wild), and by Jacob and Todd from Egyptian Cannabis indica resin. Jointly, the chemical formula for CBD (C21H30O2) was put forward by Adams from their method for isolating CBD. The structure and stereochemistry of CBD were determined in 1963 by Mechoulam and Shvo
Cannabidiol has a very low affinity for endogenous cannabinoid receptors (called CB1 and CB2), acting as an antagonist of these receptors. It increases the concentration of synaptic anandamide by inhibition of its reuptake and by hydrolysis of the enzyme FAAH (fatty-acid amide hydrolase).
It acts on pain receptors or the serotonergic system as an agonist of 5-HT1A receptors, and other opioid receptors. It acts by desensitizing ion channels, but also by antagonizing the 5-HT3A serotonergic receptor. It would also act by potentiating the analgesic effect of THC.
Cannabidiol is an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 as well as CYP3A4. Its elimination from the body is slow (half-life of 56 to 61 hours orally and 31 hours if smoked) and essentially hepatic.
Since its large-scale commercialization, CBD has been the subject of numerous scientific studies intended to find therapeutic applications, which however remain weak at present despite the claims of sellers. In fact, according to Professor Nicolas Authier, “Scientific evidence of the therapeutic benefit of CBD alone (without THC) is rare, with the exception of certain forms of drug-resistant epilepsy for which a drug is already available in France. (Epidyolex).” “Well-being” claims are subjective and unverifiable, and mainly serve as a mercantile argument. The French health authorities recalled in a decree of December 30, 2021 that “Products containing CBD cannot, under penalty of criminal sanctions, make therapeutic claims, unless they have been authorized as a medicine. » Currently, only one medicine containing purified cannabidiol is authorized in France: Epidyolex. It falls under the regulation of poisonous substances.
However, some clinical studies have demonstrated neurological interactions with cannabidiol.
CBD has been studied for the treatment of seizures, inflammation, anxiety, insomnia and nausea, as well as inhibiting the growth of cancer cells. It may also have medical potential in relieving symptoms of dystonia and treating epilepsy, schizophrenia, social phobia and autism spectrum disorders.
Popular for relieving chronic pain, some researchers conclude that the evidence is insufficient to determine the effectiveness of CBD for pain, mainly because of the difficult access to pure CBD.
The growing popularity of CBD has sparked much research into its potential therapeutic effects. Although studies are still ongoing, there are indications that CBD may have analgesic, anti-inflammatory, anxiolytic and neuroprotective properties.
CBD products have gained popularity as dietary supplements and natural remedies. However, it is important to point out that regulations surrounding CBD vary from country to country, and it is essential to comply with local laws when using it..
It should also be noted that the concentration of CBD may vary from product to product, and it is recommended to choose reputable and transparent brands to ensure product quality and purity.
As with any dietary supplement or health product, it is always best to consult a healthcare professional before beginning any new use of CBD, particularly if you are already taking medical treatment.
In November 2007, researchers at California Pacific Medical Center saw promising results against metastatic breast cancers. In vitro research has demonstrated the deactivation of the ID1 gene, responsible for the spread of cancer cells (breast and other types of cancer). The molecule acts by destroying cancer cells while leaving healthy cells intact through apoptosis. For the treatment of cancer, an association with Δ9-THC is sometimes necessary
Epilepsy is a neurological disease, disrupting the functioning of the brain. CBD was first tested in 2011 on a 5-year-old girl from Colorado named Charlotte Figi, who had a rare form of epilepsy and was made famous by Dr. Sanjay Gupta (medical chief of the US news channel CNN) in 2013. Early reports reported seizure reductions of at least 50%, and some were seizure-free for a full week. The molecule is administered to the patient by mother tincture (in the form of an oil), extracted from the cannabis plant.
A special strain, called "Charlotte's web", with high CBD (17%) and low THC (0.2%) was developed by an American non-profit association called Realm of Caring. An American bill initiated by Republican Senator Scott Perry on March 25, 2015 and which aims for the national legalization of CBD is filed on the White House website. Australia is beginning to recognize its use for the treatment of epilepsy. A case has been recorded in France.
GW Pharmaceuticals is developing a drug similar to this American variety called Epidyolex. After several months of clinical trials, the drug received its marketing authorization from the European Union on September 23, 2019 as a complementary treatment to existing therapeutic offers.
Cannabidiol does not appear to have any notable intoxication effects on the cardiovascular system and does not cause tachycardia. Research indicates cannabidiol may reduce side effects of THC.
In children (without prescription), pregnant women or people with liver or kidney disease, taking CBD is not recommended.
A recent systematic review studied the side effects of oral CBD, including only randomized, double-blind, placebo-controlled clinical studies in this review. The most statistically significant side effects found in CBD patients, compared to placebo, are: gastrointestinal symptoms, change in appetite (loss or increase), rash and increase in liver enzymes (ALT/AST). Other symptoms such as drowsiness and fatigue are very commonly reported. At the same time, they found drug interactions with other medications, particularly in cases of taking CBD for epilepsy, there are interactions with other antiepileptic medications. Another review41 finds the same side effects.
The Vidal guide also warns of the effects and drug interactions of CBD (Epidyolex): impairment of the ability to drive vehicles, food interaction with alcohol, risk of increased transaminases, risk of weight loss, risk drowsiness, suicidal risk, drug interactions (St. John's wort, anticonvulsants, fentanyl, alfentanil, etc.).
The French Association of Addictovigilance Centers also published a bulletin on CBD in 2020, then a note in 2021, warning about interactions with other medications (antiepileptics, anticoagulants, immunosuppressants and methadone). In addition, CBD presents a potential danger for pregnant women. Indeed, studies carried out in vitro and in vivo on rats have demonstrated reproductive toxicity, however, to date no studies have been carried out on humans. Likewise, as a precautionary measure, Vidal advises an interruption of breastfeeding.
Many synthetic cannabinoid derivatives have been created due to market newness and lack of consumer information, but these have absolutely not been tested for human consumption, so they are labeled as incense, but may present many potential dangers.
This was the case for HHC, which was marketed for several months, banned on June 12, 2023, following its classification in the category of narcotics.
Furthermore, inhaling or ingesting synthetic products whose safety has not been verified may seem, rightly, questionable.
CBD-carboxylic acid is produced in cannabis via the same metabolic pathway as THC, until the final step, which is catalyzed by CBDA synthase instead of THCA synthase
- The supercritical CO2 extraction technique: The CO2 extraction technique is certainly the most specific method because it allows CBD to be isolated from all other cannabioides. It is therefore ideal for having the purest CBD possible but, consequently, does not have the advantage of extracting all the compounds and thus keeping the entourage effect..
- The solvent extraction technique: The solvent extraction technique is much less specific but has the advantage of extracting all the compounds and thus retaining the entourage effect. This technique is at the origin of the so-called full Spectrum oils.
- Extraction with vegetable glycerin: Extraction with a glycerol type alcohol makes it possible to extract all the cannabinoids. This patented process consists of macerating cannabis sativa in glycerol, in order to gradually extract almost all of the active compounds present in CBD flowers, including terpenes. Terpenes are organic compounds responsible for the distinct aromas and flavors of cannabis plants. When preserved in CBD extraction, they significantly improve the taste of hemp flower extracts, allowing users to enjoy a more pleasant experience without having to flavor the extract.
Only two French companies, the Ecosystem laboratory marketing its products via a network of partner sellers, and Mengaia Natural operating the H2O CBD brand on the internet, offer this type of product, resulting from maceration in glycerol, this process being patented and exclusive of use. However, water-soluble extracts obtained without maceration in glycerol have recently been offered on the French market; scientific studies will have to determine whether the results obtained are similar..
A 2019 study found that water-soluble CBD had 4.5 times higher bioavailability than oil-based CBD, the most common form on the market. This means that with an equivalent quantity integrated into the human body, this form of CBD is better absorbed and thus presents more intense effects.
Presence of cannabidiol in industrial hemp
The industrial variety Fédora 17 contains 1% of cannabidiol on the total mass: i.e. 10 g of pure substance per 1 kg.
Extraction can be done with olive oil, ethanol or CO2.
4,000 tonnes of industrial hemp are produced per year in France, 23,000 tonnes in China.
Legislation
There are four different possibilities for legislation: total illegality (in most countries in Africa and the Arab world, for example), legality (United States and some Anglo-Saxon and European countries), decriminalization (some countries) and therapeutic exemption (many European countries). In all countries where cannabis in general is legal, CBD is naturally too.
Often, CBD falls under the scope of cannabis legislation (by confusion with THC although CBD does not have psychoactive properties according to the WHO), or is tolerated without products containing THC being tolerated, and without laws explicitly indicating it: the legislation is still very imprecise on this subject, and probably intended to evolve.
The production and distribution of hemp flowers is now legal in France, new varieties are being developed in Europe, which can be cultivated by professionals provided they have been registered in the European seed catalog. these reach levels of 12 to 14% cannabidiols, and comply with the maximum European level of 0.3% THC.
-Suisse: CBD is not regulated by the Narcotics Act. It can therefore be sold legally as long as it contains less than 1% THC
-France: In 2013, Marisol Touraine asked the ANSM to study the SATIVEX file (nabiximols, medicine based on cannabis extracts, THC and CBD). Marketing authorization was obtained at the beginning of January 2014. It is indicated for the treatment of "spasticity in multiple sclerosis after failure of other therapies" and reimbursed at 15% from October 2014 but marketing is still not taking place in 2018 in due to a disagreement over the sale price, despite questions in the National Assembly and the expectations of patients.
Entrepreneurs have opened businesses, allowing the distribution of hemp-derived products based on CBD, the plants not having to exceed 0.2% THC concentration, and 0% in processed products such as oils, capsules, etc. -liquids and boosters.
In September 2019, the Bordeaux court ruled in first and last instance that the French law was unconventional: French law does not comply with European texts on industrial hemp.
In November 2020, the Court of Justice of the European Union ruled that the ban in France on the marketing of cannabidiol was illegal, following the trial between the company Kanavape and the French State, emphasizing that this molecule present in the Hemp (or Cannabis sativa) has “no psychotropic effects or harmful effects on human health”. Mildeca recognizes the legality of cannabidiol but prohibits any therapeutic claims. The Kanavape case is referred to the Aix-en-Provence Court of Appeal which must definitively judge this case.
In June 2021, the Court of Cassation lifted the legal uncertainty surrounding CBD and its marketing. It is considered legal in its form derived from the plant of the variety Cannabis sativa subsp. sativa, but the status of the flowers themselves is not clarified in the judgment.
The government regulated the production and distribution of industrial hemp (from which cannabidiol is derived) by the decree of December 30, 202161 and defined the THC limit at 0.3%. It authorizes the sale of processed hemp products as well as the exploitation of floral tops (flowers and leaves) but prohibits their sale to the general public. The government justifies this decision in order to facilitate the work of public forces (THC/CBD differentiation) but also for public health issues. Which in the opinion of legal experts is not in accordance with the law. A priority question of constitutionality was subsequently asked by the French Association of Cannabinoid Producers. On January 7, 2022, the Constitutional Council therefore clarified the criteria for defining a narcotic product: this term designates a psychotropic substance which is characterized by a “risk of dependence” and “harmful effects on health”, which could exclude CBD. On January 24, 2022, the Council of State invalidated the ban on the sale of flowers and raw leaves of Cannabis sativa containing less than 0.3% THC. In 2023, the regulations on CBD (cannabidiol) in France have undergone significant changes. On December 29, 2022, the Council of State issued an announcement to formalize the legalization of CBD throughout France. Thus, in 2023, Cannabidiol with a THC level of less than 0.3% is legal.
The authorization as a “new food” by the European Food Safety Authority has not yet been validated, pending additional data on its safety of use. Food products containing CBD are therefore not formally authorized in Europe, although they are available on the French market.
The Council of State lifted the ban on the sale of hemp flower and leaf loaded with cannabidiol on December 29, 2022
-Pays où le cannabis et ses composés sont légaux de manière générale: This is the case of 8 American states such as Colorado and Washington DC, Argentina (since 2013), Canada (since 2018), Mexico, Peru, South Africa, Georgia and South Korea.
Austria accepts the use of cannabis in small quantities for strictly personal use, but not sale.
India, Pakistan and Nepal tolerate its use (particularly privately or religiously) without it being really legal..
In Morocco, cannabis is tolerated in the Rif region.
-Pays où le CBD est dépénalisé: In some countries, production, sale and possession in large quantities generally remains illegal, but consumption is not subject to repression..
This is the case in Jamaica (as for cannabis in general), Colombia, Italy, Portugal, Croatia, Belgium, the Netherlands, Luxembourg (“decriminalized”), Denmark, Germany, in the Czech Republic, Russia and Australia.
Spain tolerates the use of cannabis only in dedicated places.
Some countries tolerate the cultivation and sale of cannabis and its derived products as long as the THC level remains below 0.3% (without specific mention of cannabidiol): Croatia, Denmark, Italy, Portugal and France.
- Countries where CBD is authorized for therapeutic purposes:
- In America:
This is the case for Chile, Colombia, Argentina, Mexico, Uruguay and Brazil..
- In Africa:
Zimbabwe, Lesotho.
-En Europe:
United Kingdom, Norway, Finland, Spain, Netherlands, Germany, Switzerland, Poland, Lithuania, Czech Republic, Austria, Slovenia, Italy, Macedonia , Greece and Turkey.
-En Asie:
Sri Lanka, Thailand, South Korea, Israël, le Liban.
- In Oceania:
Australia, New Zealand.
- Pays où le CBD est interdit:
CBD, like all cannabis derivatives, remains prohibited in virtually all of Asia (except Sri Lanka, Thailand, and South Korea), the Arab world (except Lebanon and the Rif) and all of Africa (except South Africa, Zimbabwe and Lesotho).
In some countries, the penalties can be as heavy as in the case of hard drugs: thus in 2021, a British man was sentenced to 25 years in prison in Dubai for the simple possession of a little CBD oil
Cannabidiol sold since 2018 in stores and online sites has generated a new market and different ways of consuming it have appeared :
-Huile de CBD : CBD oil is made by extracting the molecule from the cannabis plant by diluting it in a carrier oil such as coconut oil, olive oil, or hemp oil. It is available in the form of a bottle with a pipette, reminiscent of drip at different concentrations (from 5% to 20% on average). The rise of CBD around the world has generated strong demand for this product. You should be careful about the traceability and manufacturing of the oil and carefully choose the company from which you wish to obtain this product.
- Water-soluble CBD extracts: Water-soluble CBD extracts are different from CBD oils in that they typically contain glycerol. They are obtained by a process of maceration of cannabis sativa in glycerol. The extraction process of the CBD molecule makes them soluble in water, which greatly facilitates their consumption since they can be ingested directly or incorporated into drinks. Their taste is very close to the cannabis plant and is sweet due to the glycerol. They are generally sold in bottles with pipette.
- Dried flowers : The dried flowers resemble those found on the cannabis black market but contain only a legal level of 0.2% THC. They are intended to be infused in a fatty substance (such as milk or oil). The CBD rate varies from 3% to 8-9% depending on the profile. Manufacturers add terpenes to give these flowers a variety of tastes.
- CBD crystals : The crystals are CO2 extracted to isolate the molecule from the rest of the cannabinoids. They are used to create concentrated CBD products.( not really effective in terms of effectiveness the 100:0 cbd:thc ratio does not really have any effect)
-e-liquides & boosters : CBD can be consumed via electronic cigarettes. It is available in stores and online in the form of an already ready E-Liquid or in the form of a booster like nicotine boosters to add to an already ready E-Liquid or to a D.I.Y preparation. CBD concentrations are measured in mg/10 ml, they generally vary from 100 mg/10 ml to 1,500 or even 2,000 mg/10 ml for high concentration products..
There are also so-called “full-spectrum” E-Liquids and boosters, in addition to CBD, they incorporate other cannabinoids (but obviously not THC or other psychotropic compounds) such as Cannabidivarin (CBDV). ) and Cannabigerol (CBG) and terpenes present in the hemp plant. These preparations boast the association of these various cannabinoids and their complementary and potentiated actions (entourage effect).
- Teas and Infusions: Consuming a cup of CBD tea allows you to benefit from the effects of CBD, tea and all its different ingredients (ginger, cloves, etc.).
-Capsules : CBD capsules contain CBD oil coupled with other substances (such as melatonin). These capsules are hard or soft. They constitute a practical way to precisely control your CBD dosage.
Other phytocannabinoids found in hemp
