Science

What are Cannabinoids?

Cannabinoids are a diverse class of chemical compounds that occur naturally in the human body (endocannabinoids) and cannabis plants (phytocannabinoids), and interactions with the endocannabinoid system (ECS) trigger various physiological actions. Among the 500 or so natural components in cannabis, more than 100 are classified as phytocannabinoids. Tetrahydrocannabinol (THC) is the best-known compound due to its psychoactive qualities, while cannabidiol (CBD) appears to play the most significant role in the plant’s medicinal benefits. Other key phytocannabinoids include the following:

  • Cannabigerols (CBG)
  • Cannabichromenes (CBC)
  • Cannabinol (CBN)
  • Cannabinodiol (CBL)

CBD, which does not produce psychoactive effects, is often isolated for medical use, but some clinical studies suggest that cannabinoids are mutually enhancing and provide the best results in whole-plant form. CBN, another cannabinoid gaining interest with medical researchers, is a natural sedative that appears to have analgesic, anti-inflammatory and anti-convulsive properties. Endocannabinoids, meanwhile, include anandamide and 2-Arachidonoylglycerol (2-AG), and they play roles in metabolism, food intake, memory, sensory perception, central nervous system development and synaptic plasticity.

Cannabinoid Receptors

Cannabinoid receptors are embedded in the cellular membrane in the central nervous and immune systems as well as in various organs. Both endo- and phytocannabinoids bind to these receptors or influence them indirectly. As external environments and stressors change, the ECS helps the body maintain a stable biological environment, or homeostasis. The importance of the system is such that drug companies manufacture synthetic cannabinoids to replicate artificially the natural processes produced by the body and cannabis plants. The pharmaceutical product is widely considered inferior.

The two main ECS receptors are type 1 (CB1) primarily in the central and peripheral nervous system and type 2 (CB2) primarily in the immune system. Some cellular tissue contains both types performing their respective actions. While THC binds directly to cannabinoid receptors, CBD affects them indirectly by stimulating endocannabinoid production in the body and suppressing the enzyme that metabolizes the natural chemicals. Furthermore, CBD and CBN are both examples of phytocannabinoids that bind to non-cannabinoid receptors, including 5-HT1A (serotonin), TRPV1 (pain, inflammation) and adenosine A2A (cardiovascular, respiratory).

How Cannabinoids Work

The ECS is responsible for physiological processes like appetite, pain sensation, mood and memory, and cannabinoids mediate communication between various cells and systems. Its receptors, when activated, trigger various chemical, natural and pharmacological effects relating to how we feel, both mentally and physically. Phytocannabinoids work their magic by imitating the endocannabinoids produced naturally in the body.

Some researchers suggest the system serves as a bridge between the brain and the body, and the area of the brain with which the cannabinoids bind dictates the way the cannabis will affect the person. These areas include the limbic system, which affects memory, cognition and psychomotor performance; the mesolimbic pathway, the part of the brain associated with feelings of reward; and various parts of the brain associated with pain perception. Medical cannabis treatments are largely based on the practice of aiming the right cannabinoids at the right receptors.

Interestingly, the cannabis plant also uses cannabinoids to promote its own health. The compounds have antioxidant properties that protect the leaves and flowering structures from ultraviolet radiation. In other words, cannabinoids neutralize the harmful free radicals generated by UV rays, protecting the cells. In humans, free radicals cause aging, cancer and impaired healing, and the medical community has long promoted antioxidants as a natural way to reduce free radical harm.

Cannabis as Medicine

Cannabis, with its naturally occurring cannabinoids, has been used for medicinal purposes for thousands of years. The U.S. Food and Drug Administration (FDA) has yet to approve cannabis as a treatment for any medical condition. However, the National Institutes of Health (NIH) owns patent No. 6630507 on the neuroprotectant properties of cannabinoids, and the National Institute on Drug Abuse (NIDA) says whole-plant marijuana appears to slow cancer growth and potentially kill certain types of cancer cells. NIDA also acknowledged that THC reduces nausea and muscle control problems, while CBD has therapeutic potential for childhood epilepsy, seizures, mental health disorders, addiction and other serious conditions. Both cannabinoids provide relief from pain and inflammation.

The ECS is named after the cannabis plant, and researchers studying the plant actually led to the discovery of the system. Fittingly, researchers are finding that other plant life, such as echinacea, also contain helpful cannabinoids. A side benefit from research into cannabis compounds is a better understanding of how other medicinal herbs might also promote physical and mental health.

Cannabidiol (CBD)

Cannabidiol, also known as CBD, is a naturally occurring chemical found in cannabis. It is one of the most highly concentrated and studied compounds among the more than 100 compounds, or cannabinoids, found in the plant. While it does not cause users to get high, cannabidiol has numerous health benefits.

Although cannabidiol still requires further study to know all of its health benefits, scientists have been able to pinpoint some of the medical uses of the compound. CBD can help treat nausea and vomiting, making it a useful choice for cancer patients. Cannabidiol may also help shrink the growth of cancer and tumors. It may help people who suffer from psychoses, anxiety and depression. Inflammation and neurodegenerative effects, such as those with Alzheimer’s disease, may be reduced through the use of CBD. Oil made from the compound could even be used to treat forms of epilepsy in children. Its calming effects are also useful for people with social anxiety disorder.

When people cite the so-called negative effects of cannabis, they are usually due to the presence of  tetrahydrocannabinol (THC), the compound that causes the psychoactive effects. Some of these, such as paranoia and increased levels of stress, may be negated by the balancing power of cannabidiol. The chemical can help increase feelings of calm and self-awareness to make it safer for patients to use cannabis for medical treatment without risking common side effects. Since each patient reacts differently to treatment, some may experience differing effects that can occur during cannabis consumption.

Smoking is not a requirement for using cannabidiol. In fact, the ingredient can be utilized from a variety of products. The most common of these is cannabidiol oil, followed by cannabidiol pills. Many patients who use CBD do not smoke but use a medicine dropper to deliver their medication to their bodies. Pastes, capsules, sprays and salves are also available, providing consumers with many choices. Cannabidiol oil can even be used in vaporizers. Patients should begin with small dosages before increasing the amount of CBD taken daily.

As the benefits of CBD continue to become known, growers are modifying their crops to account for more cannabidiol and less tetrahydrocannabinol to create stronger medicinal plants. Some politicians believe that all plants with THC should be kept illegal, and as CBD plants become more commonly produced, doctors remind them that both compounds have certain benefits to be had by patients. The anti-nausea and appetite stimulating properties of THC make it an optimal treatment for some patients, depending upon their conditions and symptoms. Research also shows that the two compounds work best when together.

Sleep disorders, schizophrenia and glaucoma may all be cured one day after more studies are complete regarding cannabidiol. Some popular strains of cannabis grown with increased CBD levels and little THC content include AC/DC and Charlotte’s Web. Island Junk and Hawaiian Dream are also high in cannabidiol.

Cannabinol (CBN)

Cannabinol (CBN) is a phytocannabinoid, one of at least 100 such chemical compounds that exist in the cannabis plant. Medical studies to date focused primarily on cannabidiol (CBD) and tetrahydrocannabinol (THC), but interest in CBN as a medicinal agent continues to gain momentum. Extensive clinical research is still in the works, but CBN appears to play a primary role in the sedative effects of cannabis. Indica strains tend to have higher amounts of CBN, though overall amounts in any strain are small compared to CBD and THC.

The endocannabinoid system (ECS) helps the body maintain biological stability against changes in a person’s environment. The phytocannabinoids in cannabis can bind to or indirectly affect ECS receptors in the body promoting healthy communication between cells and various physiological processes with potential medicinal benefits. Though THC binds directly to ECS receptors, both CBN and CBD influence them indirectly and bind to other non-cannabinoid receptors in the body. According to various clinical studies conducted so far, CBN has several potential treatment applications, including the following:

  • CBN is primarily utilized as a sleep aid for individuals suffering from insomnia
  • A 5mg dose of CBN may provide the same sedative effects as 10 mg of diazepam (Valium)
  • The cannabinoid appears to influence functionality in the immune system
  • Studies suggest that CBN might promote bone growth and help treat osteoporosis
  • CBN may also have analgesic, anti-inflammatory and anti-convulsive benefits

A study published in the Journal of Natural Products in 2008 also found that CBN (and other cannabinoids) demonstrated “potent activity” as an antibacterial agent when applied topically to burns and psoriasis.

Look closely at the word tetrahydrocannabinol and note that cannabinol (CBN) is in the name. In fact, various factors can convert THC into CBN, a process that includes the following:

  • Cannabigerolic acid (GBGA) is a chemical component in cannabis
  • The plant produces enzymes that convert CBGA into various cannabinoids
  • One such cannabinoid is tetrahydrocannabinol carboxylic acid (THCA)
  • The decarboxylation of THCA (usually through heat) converts it into THC
  • THCA also converts to CBNA when it loses hydrogen molecules and oxidizes
  • The latter process (THCA to CBNA) occurs through prolonged exposure to air
  • Like THCA becoming THC, decarboxylation converts CBNA into CBN

Herein lies the irony: Old cannabis that is improperly stored and cured has the highest amounts of CBN. When properly stored, dried flowers are unlikely to top one percent CBN. As the product of THC degradation, CBN is most common in what most people consider poor quality cannabis. Individuals seeking the medicinal benefits of CBN might wish to air-age inexpensive cannabis, but with demand growing, CBN-rich oils, edibles, patches and other delivery devices will become increasingly more available.

Tetrahydrocannabinolic Acid (THCA)

Tetrahydrocannabinolic acid (THCA) is the biological precursor to tetrahydrocannabinol (THC), and THC in either form is a cannabinoid that interacts with the endocannabinoid system (ECS) in the body. THCis found in raw cannabis, and people seeking to enjoy its benefits often juice raw cannabis plants since it's no longer present once heated. 

What most people do not realize is that cannabis plants do not contain much THC. Rather, the plant contains THCA that becomes THC through a process called decarboxylation that releases carbon dioxide (CO2) from the chemical compound. The chemical reaction can happen using UV lights to dry the plant, but it happens quickly under intense heat. This is why eating fresh cannabis does not produce psychoactive effects, but heating the plant with a lighter and inhaling the fumes does.

THCA can also convert into a different chemical compound if exposed to air for extended periods of time. Just as decarboxylating removes carbon atoms, exposure to air causes THCA to lose hydrogen and oxidize, which converts it into cannabinol acid (CBNA). The same decarboxylation process can then turn CBNA into cannabinol (CBN), which plays a primary role in the sedative effects of cannabis.

THCA by itself might not have psychoactive properties, but studies suggest it has potential medical applications, including the following:

  • Phytomedicine in 2012 described THCA as a neuroprotectant
  • Biological and Pharmaceutical Bulletin in 2011 found anti-inflammatory properties
  • British Journal of Pharmacology in 2013 said it reduces nausea and vomiting
  • The Journal of Pharmacology and Experimental Therapeutics in 2006 noted antitumor qualities

In 2009, Trends in Pharmacological Sciences published an extensive study titled “Non-Psychotropic Plant Cannabinoids” that said early research suggests possible therapeutic applications for prostate cancer, pain relief and muscle spasms. However, cannabidiol (CBD) is likely a more effective cannabis compound in treating most conditions.

Generally speaking, clinical studies involving THCA are limited, and medical applications and efficacies for now are largely based on preliminary research, anecdotal evidence and studies into other cannabinoids. Still, it is possible that THCA can provide health benefits similar to THC but without the psychoactive effects. A common way to consume THCA is by juicing raw parts of the cannabis plant and combining the liquid with other fruit and/or vegetable juices.  

Anandamide

Anandamide (AEA) is a cannabinoid naturally produced by the body that closely mimics THC. When THC enters your body, it binds with the same receptors that anandamide does (CB1 and CB2 in the central and peripheral nervous systems), thereby activating neurons in the body. Anandamide is a fatty acid neurotransmitter that regulates activities such as mood, appetite, feeding behavior, memory and neural-generated motivation and pleasure. Studies also suggest that anandamide mediates exercise-related euphoria known as runner’s high.

2-AG

2-Arachidonoylglycerol (2-AG), the second most common endocannabinoid, is known for its effect on the central nervous system. It is formed through a complicated process involving arachidonic acid, which contains a substance known as DAG that reacts with glycerol. This endocannabinoid is essential for regulating the immune system, and it may also assist with pain management. Some research also shows that 2-AG may inhibit cancer cell proliferation.

Naturally Produced

Advocates for medical marijuana claim that individuals with certain health conditions do not make enough cannabinoids on their own in the same way that diabetics do not make an adequate amount of insulin. A lack of cannabinoids can affect anandamide, which binds to CB1 receptors in the brain, or 2-AG, which binds to CB2 receptors in your immune system. Consuming plant-based cannabinoids compensates for the lack of endogenous cannabinoids in the same way as synthetic hormone replacement does in postmenopausal women.

The fact that the brain naturally makes cannabinoids helps explain why marijuana has numerous medical uses. The science behind endocannabinoids has been known for some time, yet it is not yet widely taken advantage of due to restrictive laws. Proponents for medical marijuana hope that raising awareness will lead to legislative reform allowing more people to benefit from marijuana’s healing properties.

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