Cannabinoids: A comprehensive exploration

Cannabinoids: A comprehensive exploration

Cannabinoids, a diverse group of chemical compounds, play a crucial role in interacting with the endocannabinoid system (ECS). Present both in the human body as endocannabinoids and in plants such as cannabis as phytocannabinoids, these compounds regulate various physiological functions, including sleep, hormone balance, pain transmission, inflammation, and appetite.

There are three main categories of cannabinoids:

• Phytocannabinoids - cannabinoids produced by plants
• Endocannabinoids - cannabinoids naturally produced by the body
• Synthetic cannabinoids - artificially produced cannabinoids

When it comes to cannabinoids, most people think primarily of the compounds produced in cannabis. To date, 144 different cannabinoids have been identified in the cannabis plant, with more being added every few years.

Phytocannabinoids

Phytocannabinoids are compounds that mimic the effects or structure of the body's own cannabinoids (endocannabinoids). They affect the receptors in the endocannabinoid system by either activating or blocking them. The cannabis plant is the most extensive natural source of phytocannabinoids, containing around 144 different compounds. Each of these compounds has a unique effect on the body.

While some phytocannabinoids stimulate receptors in the endocannabinoid system, others inhibit them. CBD stands out for its regulatory function - it can both increase and decrease ECS activity to bring the entire system into balance. In the following section, we'll take a closer look at the most common phytocannabinoids produced by the cannabis plant and discuss how they work and their health benefits.

• Delta-9-THC (Δ9-tetrahydrocannabinol): Delta 9 THC, the main psychoactive compound in cannabis, stimulates endocannabinoid receptors and induces a range of effects from sedation to euphoria. Known for its appetite-stimulating, calming and anti-inflammatory properties, it has also shown potential to reduce nausea. Its legal status varies around the world, and it is used for various therapeutic purposes.
• CBD (Cannabidiol): CBD, a non-psychoactive cannabinoid, gained popularity due to its diverse health benefits. It exhibits anti-inflammatory, anti-anxiety and neuroprotective properties. CBD is widely used for conditions such as chronic pain, anxiety disorders and epilepsy.
• CBC (Cannabichromene): CBC ranks third after THC and CBD as the most abundant cannabinoid found in the cannabis plant. Unlike CBD, it is not psychoactive, but it offers a slightly different range of benefits. Although CBC has been studied less compared to CBD, there is evidence that it may show promise in inhibiting the growth of cancer cells, relieving pain, and protecting neurons in the brain. Studies have also shown that CBC can reduce sebum production, which helps suppress the formation of acne. In animal studies, CBC was found to exhibit significant antidepressant effects in mice at a dose of 20 mg/kg.
• CBG (Cannabigerol): CBG, considered the "parent cannabinoid," has gained attention for its potential in treating glaucoma, inhibiting cancer cell growth, and neuroprotective effects. It is known for stimulating appetite, relieving anxiety, and inhibiting bacterial growth.
• CBCV (cannabichromvarin): Although limited information is available about CBCV, studies suggest potential antispasmodic and anticarcinogenic effects. It may slow the growth of cancer cells and relieve epileptic seizures.
• CBGM (Cannabigerol monomethyl ether): A lesser-known cannabinoid, CBGM shares structural similarities with CBG. With potential neuroprotective and appetite-stimulating benefits, CBGM requires further research.
• CBGV (Cannabigerovarin): CBGV shows potential in pain relief by stimulating vanilloid receptors associated with pain transmission. Studies suggest its potential to support skin health and protect the gastrointestinal tract from inflammatory conditions.
• CBL (Cannabicyclic Acid): Little is known about the effects of CBL. Previous studies have mainly focused on mapping its chemical structure.
• CBN (Cannabinol): CBN, a metabolite of THC, is not psychoactive but exhibits strong sedative properties. Animal studies suggest neuroprotective effects, appetite stimulation, and relief of diseases such as ALS and glaucoma.
• CBV (Cannabivarin): CBV, an analogue of CBN, has structural similarities. While its effects have not been extensively researched, experts suspect similar effects due to structural similarities to CBN.
• Delta-9-THC (Δ9-tetrahydrocannabinol): The main psychoactive compound, delta-9-THC is known for its appetite-stimulating, sedative and anti-inflammatory effects. Its legal status varies around the world, and it is used for various therapeutic purposes.
• Delta-8-THC (Δ8-tetrahydrocannabinol): Delta-8-THC, an analogue of delta-9-THC, has about half the psychoactive potency. It serves as an alternative with similar effects but fewer side effects.
• THCV (tetrahydrocannabivarin): As a minority compound, THCV has gained attention for potentially reducing the psychoactive effects of THC. It may also affect insulin sensitivity, neurological disorders, acne prevention, and bone health.

Endocannabinoids

Endocannabinoids are compounds produced in the body that interact with the ECS.

Two key endocannabinoids, anandamide and 2-AG, are responsible for the majority of activity in the ECS. Other compounds such as OAE, NADA and LPI contribute to a smaller percentage of activity in specific tissues.

Eicosanoids are the category in which endocannabinoids are classified, and they are made from arachidonic acid. The body produces various eicosanoids that serve as chemical messengers to manage inflammation, allergies, immune activity, pain transmission, cell growth, reproductive cycles, and other functions.

• Anandamide: Dubbed the “happiness molecule,” anandamide regulates the ECS and is found in various body tissues, contributing to feelings of joy and contentment.
• 2-AG (2-arachidonoylglycerol): As the second most important endocannabinoid, 2-AG plays a significant role in ECS activity and acts as an agonist for CB1 and CB2 receptors.
• OAE (O-arachidonoylethanolamine): OAE (virodhamine) acts as a full agonist for CB2 receptors and a partial agonist for CB1 receptors, but is less studied than anandamide and 2-AG.
• NADA (N-arachidonoyl dopamine): NADA, which binds to CB1 and vanilloid receptors, has similar effects to anandamide.
• LPI (Lysophosphatidylinositol): Although not yet officially confirmed as an endocannabinoid, LPI is believed to bind to GPR55 receptors. More research is needed to understand the effects of this compound and its role in the endocannabinoid system.

Synthetic cannabinoids

Synthetic cannabinoids, produced in the laboratory, are often associated with negative side effects.

Most synthetic cannabinoids share structural similarities to THC. After 2010, synthetic cannabinoids experienced a resurgence as manufacturers sought products they could sell as "legal psychoactive substances." During this time, similar cannabis products were illegal, while synthetic derivatives were legally available. Products containing these synthetic THC compounds were advertised as "legal" in stores and online.

Synthetic cannabinoids, known as "spice" or "K2," were created by spraying dried leaves with a mixture of man-made cannabinoids and then smoking them in a similar way to cannabis. These compounds became notorious for their side effects, which ranged from severe headaches to lung damage and seizures.

Today, marijuana is legal in many parts of the world, while all psychoactive substances are illegal unless they are deemed safe under the New Psychoactive Substances Act of 2013 (USA). "Spice" is now only available on the black market and remains unpopular due to the negative side effects, high risk, and easy availability of natural cannabis.

Synthetic cannabinoids do not always have the same structure as natural cannabinoids. While true cannabinoids are classified as eicosanoids, which use arachidonic acid as a base, synthetic cannabinoids take forms such as aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides. These are very different from natural cannabinoids but interact with the same receptors.

Some synthetic cannabinoids are:

• JWH-018
• JWH-073
• JWH-200
• AM-2201
• UR-144
• XLR-11
• AKB4
• Cannabicyclohexanol
• AB-CHMINACA
• AB-PINACA
• AB-FUBINACA

Pharmaceutical cannabinoids

In recent years, the pharmaceutical industry has seen significant progress in the development of new cannabinoid-based drugs. Several major pharmaceutical companies, including GW Pharmaceuticals, Solvay Pharmaceuticals, Pharmos and Valeant Pharmaceuticals, are devoting significant resources to the research and development of cannabinoid-based drugs.

Some of the pharmaceutical drugs are:

• Sativex®: A well-known pharmaceutical cannabis product from GW Pharmaceuticals, Sativex is used to treat pain in multiple sclerosis and cancer.
• Epidiolex®: Epidiolex, the only FDA-approved CBD product for the treatment of epileptic disorders, is manufactured by Greenwich Biosciences.
• Dexanabinol®: Dexanabinol, although a synthetic cannabinoid, does not interact with the endocannabinoid system. It binds to NMDA glutamate receptors and offers comprehensive neuroprotective effects.
• Marinol®: A synthetic version of delta-9-THC, Marinol is manufactured by Unimed Pharmaceuticals and is used to treat cancer and MS-related conditions, as well as to stimulate appetite in AIDS patients.
• Cesamet®: Cesamet, a synthetic THC derivative from Valeant Pharmaceuticals, treats side effects of cancer treatment.
• Cannabinor: Developed by Pharmos, Cannabinor binds exclusively to CB2 endocannabinoid receptors to reduce inflammation and relieve pain.
• CT-3: CT-3, a synthetic cannabinoid, is used to treat neuropathic pain and muscle spasticity in multiple sclerosis.
• Taranabant: Taranabant, a synthetic molecule, binds to CB1 endocannabinoid receptors to suppress appetite but never reached Phase III clinical trials due to side effects.

Cannabinoids in other plant species

Although cannabis is the main source of cannabinoids, other plants also produce compounds that can interact with the endocannabinoid system:

• Echinacea purpurea (purple coneflower): Produces N-alkylamides that interact with CB2 endocannabinoid receptors.
• Acmella oleracea: Produces N-isobutylamides, which stimulate CB2 receptors.
• Piper methysticum (Kava Kava): The active ingredient yangonin interacts with CB1 endocannabinoid receptors.
• Camellia sinensis (Chinese tea tree): The catechins of the tea tree have an affinity for the endocannabinoid receptors.
• Tuber melanosporum (Black Truffle): Contains the endocannabinoid anandamide.
• Radula marginata (liverwort): Contains the cannabinoid perrottetinene, structurally similar to THC.

Conclusion: What are cannabinoids?

In summary, cannabinoids are a broad and diverse group of chemicals that interact with the endocannabinoid system. They are present in various organs, including the skin, blood vessels, and immune system. Endocannabinoids, produced by the body, and phytocannabinoids, produced by plants like cannabis, offer an impressive range of benefits. From regulating sleep to fighting chronic pain and inflammation, cannabinoids are used as dietary supplements to address various health challenges. While THC and CBD are the most well-known, research into other cannabinoids and their pharmaceutical applications shows promising avenues for the future.





"Disclaimer and general note on medical topics:
We are not authorized to provide information about the health aspects of our products. According to legal regulations, we are prohibited from making any promises of healing.
The content on our website is intended solely for neutral information and general education purposes. It does not represent a recommendation or promotion for the diagnostic methods, treatments or products described or mentioned. The texts do not claim to be complete, nor can the timeliness, accuracy and balance of the information be guaranteed.
The texts and product descriptions listed are in no way a substitute for professional advice from a doctor or pharmacist. They should not be used as a basis for independent diagnosis or for starting, changing or ending treatment. In the event of health-related questions or complaints, you should always consult your trusted doctor."