What Are Cannabinoids?
Surely you have heard that THC is the cannabinoid that provides the euphoric high, and you even know about many of the medicinal benefits of CBD. But what do all of those other cannabinoids do? Read below to find a comprehensive summary of the most important cannabinoids and their properties.
Discovery of Cannabinoids
Cannabis is a complex plant containing at least 483 known chemical compounds. Out of that, at least 66 have been identified as cannabinoids, and some sources say there could be as many as 113.
Cannabinoids are chemical compounds which bind to cannabinoid receptors and help regulate the endocannabinoid system. Endocannabinoids are produced naturally in animals. Phytocannabinoids are found in plants such as cannabis. Humans also can create synthetic cannabinoids in the laboratory for research and medical treatment.
Cannabis has been used for medicinal purposes for thousands of years to treat pain, spasms, asthma, sleep disorders, depression, and loss of appetite. By the beginning of the 20th century, the plant started to go out of use, as scientists struggled to understand the chemical structure of the active ingredients. In order to scientifically prove the medicinal value, the underlying mechanism must first be understood.
The cannabinoids were not discovered until the 1964, when THC was stereochemically defined and its 3D structure was finally understood. It took even longer to figure out how they interact with our bodies. In the 70’s and 80’s, it was thought that the cannabinoids were activated by getting dissolved in lipids, or fats.
The discovery of THC and the other cannabinoids actually led to the discovery of the human endocannabinoid system.
Throughout the 1980’s, researchers started to realize that the potency seemed to depend highly on the 3D shape of the cannabinoid. For example, it was found that two cannabinoids with the same chemical makeup, yet different 3D structure have different effects. This suggests that the cannabinoids must bind to a specific receptor.
By 1988, the CB1 receptor was discovered and some of its properties where characterized. Since then, the CB2 receptor has been discovered, and some believe there may be a CB3 receptor.
At first, many researchers were puzzled as to why animal brains would waste the energy and resources to create receptors that only bind to cannabinoids which only seem to be naturally created in plants. This motivated scientists to try to discover compounds made within our brains that might bind to the CB1 receptors as well.
Soon enough, it was discovered that our brains have naturally occurring cannabinoids. 2-arachidonoylglycerol, or 2-AG, is an example of one discovered in humans. Anandamide is another naturally occurring cannabinoid, which is also called N-arachidonoylethanolamine or AEA. Arachidonyl glyceryl ether is yet another, and a total of five endocannabinoids have been discovered so far.
By 1993, a second cannabinoid receptor, CB2, was discovered. These receptors are located in many locations across the body, particularly in the immune system.
Cannabinoid Receptors
Cannabinoid receptors are located in cell membranes throughout the entire body. The cannabinoid type 1 (CB1) receptors are activated by THC, anandamide, 2-AG, and other cannabinoids. Activation of this receptor gives the euphoric feeling that recreational users have enjoyed for centuries.
While CB1 receptors are primarily located on nerve cells in the brain, they also appear throughout the body and in the reproductive organs. The basal ganglia, cerebellum, and limbic system are some parts of the brain containing these receptors. They are also contained in lesser amounts throughout the spinal cord, in pituitary glands, thyroid glands, fat cells, muscle cells, liver cells, white blood cells, the digestive tract, lungs, and kidneys.
When the CB1 receptors are activated, they inhibit the release of neurotransmitters such as dopamine and serotonin. As such, they can affect our appetite, memory, pain regulation, and motor control. For example, variations in the gene that leads to CB1 receptor production has been shown to be related to obesity levels.
The CB2 receptor is located primarily in immune cells throughout the human body, and is activated by CBD and 2-AG. CB2 activation helps regulate the release of cytokines, which are a class of proteins that send messages between the cells throughout the immune system.
While there currently aren’t any other known cannabinoid receptors in humans, some speculate that more could exist.
The Endocannabinoid System
The endocannabinoid system allows for cells to communicate throughout the brain and the nervous system. As a result, this system can regulate inflammation, pain, sensations, memory, and mood. Also, it can help control appetite, food intake, and energy levels.
In recent years, more scientists are starting to acknowledge that regulating the endocannabinoid system can have a wide variety of uses for improving health and treating diseases. Mood and anxiety disorders, Parkinson’s and Huntington’s disease, neuropathic pain, multiple sclerosis, spinal cord injury, cancer, stroke, hypertension, glaucoma, obesity, and osteoporosis are some examples.
The system operates by having enzymes create endocannabinoids, which then bind to the cannabinoid receptors throughout the body. Activation of the receptors can regulate the flow of ions throughout cells. This could also send a signal to the enzymes to change the creation rate of the next round of endocannabinoids.
The complexity of interactions that can occur is immense, as the receptors exist in a wide variety of cell types. To make things more complicated, each species has their own unique endocannabinoid system, with different, enzymes, receptors, and endocannabinoids.
While very little is known about the endocannabinoid system, we are starting to understand that good health requires a properly regulated endocannabinoid system.
The cannabinoids actually work a bit differently than most neurotransmitters. Our brain has over 100 billion neurons, which are brain cells that communicate by sending neurotransmitters, or chemical messages. Typically, the presynaptic neuron will send a neurotransmitter through the synapse, a small gap, before getting absorbed by a postsynaptic neuron.
What makes cannabinoids work differently is that they are actually created in the postsynaptic neuron and get sent back to the cannabinoid receptors on the presynaptic neuron. The cannabinoids tell the presynaptic neuron to limit the amount of neurotransmitter, such as dopamine, to be released.
It is now theorized that the endocannabinoid system is essential for good health. Deficiencies within the system may result in disease.
Since everyone’s endocannabinoid system is wired differently, this describes why the same cannabis plant could affect different people in different ways. While cannabis is not for everyone, some people may find that supplementing their diet with the proper combination of cannabinoids may lead to a healthier lifestyle.
Below, we summarize the most common cannabinoids contained in marijuana.
Tetrahydrocannabinol (THC)
Delta-9-THC was first isolated in a laboratory in 1964. Since then, thousands of scientific papers have been written on the interaction properties of THC. According to researcher Ethan Russo, THC is also a powerful neuroprotective, antioxidant and has 20 times the anti-inflammatory power of aspirin and twice that of hydrocortisone.
While it is thought that smoking cannot be good for the lungs and breathing, a study has shown that THC actually increases airflow in asthma patients.
While THC is primarily known for its psychoactive and euphoric effects, THC also has many medical uses, including ALS, Alzheimer’s, arthritis, cancer and chemotherapy side effects, Crohn’s disease, fibromyalgia, HIV, Huntington’s disease, insomnia, multiple sclerosis, pruritis, and Tourette syndrome.
Much research has been done with synthetically created THC, which is called dronabinol, or Marinol in some countries. In the US, patients may receive dronabinol to treat nausea from cancer treatment or appetite loss from AIDS. Nabilone is a synthetic form of THC prescribed in the UK.
While most of THC’s effects are due to activation of the CB1 receptors, they also interact in other areas as well. For example, it is thought that nausea and vomiting is reduced by an antagonistic action on the 5-HT3 receptor. As we see, THC can act in many subtle ways that are still being explored, but CB1 activation is the most noticeable effect.
Benefits include pain relief, relaxation, reduce pain and risk of nerve damage, affects anxiety levels, suppresses muscle spasms and convulsions, helps treat cancer, nausea, slows inflammation, fights free radicals in the blood stream, appetite stimulant, stimulates nerve tissue growth, reduces eye pressure and pain from glaucoma.
For more information about THC, check out our article THC: Sensational Medicine or an Abusive Drug?
Cannabidiol (CBD)
Unlike THC, CBD is non-psychoactive, yet it has many more medicinal benefits. CBD was first isolated in a lab in the 1940’s, but its structure was not identified until 1963.
By the 2000’s, it was realized that THC, CBD, and the other cannabinoids act in a synergistic manner. This means that when THC and CBD are combined, the therapeutic benefits are greater than what they would have been if just taken alone.
Also, CBD seems to counteract many of the negative aspects of THC, anxiety in particular. This was realized when scientists started synthesizing pure THC and realized that many patients found an increase of negative side effects in comparison to patients who would smoke organically grown marijuana.
The antioxidant powers of CBD are actually higher than vitamins C and E.
Since everyone initially recognized the psychoactive potency of THC, breeders and cultivators over the past half century have almost exclusively grown high-THC strains, reducing the amount of CBD available in most strains today to less than 1%. Many older landraces from different parts of the globe used to have more equal levels of THC and CBD. Now, any strain with at least 4% CBD is considered high-CBD.
As more people are learning about the medicinal benefits of cannabis, some select growers specialize in exclusively high CBD strains, such as ACDC, Cannatonic, or Harlequin.
CBD helps treat many medical conditions, including ADD/ADHD, anxiety, arthritis, cancer, diabetes, Dravet syndrome, epilepsy, glaucoma, Huntington’s Disease, mood disorders, multiple sclerosis, Parkinson’s Disease, and Alzheimer’s. Some also claim that CBD helps with acne.
The benefits of CBD include anticancer properties, pain relief, stimulating bone growth, stopping growth of bacteria (antibacterial), suppressing muscle spasms and convulsions, slowing inflammation, reducing blood sugar levels, reducing risk of artery blockage, decreasing pressure in the blood vessel walls, helping with epileptic seizures, reducing risk of nerve damage, decreasing the anxiety of THC and nausea, reducing function in the immune system, treating psoriasis, and vasorelaxant properties.
To learn more about CBD, read our article CBD: The Comeback Kid of Cannabinoids.
Cannabinol (CBN)
CBN stems from cannabigerolic acid and produces a highly sedated effect. THC will eventually break down into CBN when exposed to light or oxygen, so weed that has been sitting around for a few months will have more CBN and create a stronger body high. Also, eating edibles tends to lead to more CBN than smoking, as more of the THC gets broken down into CBN by the time they activate receptors throughout the body.
CBN increases testosterone production and plasma concentration of follicle-stimulating hormone. CBN binds to the CB2 receptor at a three-times greater affinity than the CB1 receptors. It acts as a weak agonist against both of these receptors.
CBN is said to be antiepileptic, antispasmodic, antidepressant, anticonvulsive, and relieves eye pressure. CBN may also help with glaucoma, inflammation, and insomnia. However, most people do not look to CBN for medicinal value, as it can make people feel groggy.
CBN also acts as a sleeping aid, fights free radicals in the blood stream, helps with pain relief, suppresses muscle spasms and convulsions, and slows inflammation.
Want to learn more about what medical research has to say about CBN? Check out our article CBN: The Lazy Stoner’s Cannabinoid.
Cannabichromene (CBC)
CBC is typically only found in tropical strains of cannabis. CBC seems to have better antifungal and antibacterial properties than THC and CBD, which may make it a great candidate for topical products in the future.
CBC, like THC and CBD, also inhibits tumor cell growth, most likely by interacting with anandamide. Believe it or not, many strains will contain more CBC than CBD.
Benefits include pain relief, stopping growth of fungi, slowing inflammation, antibiotic, antidepressant, stimulating bone growth, encouraging cell growth, stopping the growth of bacteria, assisting in contraction of blood cells, and inhibiting cancer cell growth.
To read more about CBC, take a look at our article CBC: The Top Secret Cannabinoid.
Cannabigerol (CBG)
By the time you are getting your cannabis, almost all of the CBG will be gone. However, it is the biosynthetic precursor to THC, CBD and CBC, making it essential for production of these cannabinoids in the plant. Technically, CBGA is the precursor, which will turn into CBG.
CBG acts as a low-affinity antagonist at the CB1 receptor, and its activity with the CB2 receptor remains unknown. Overall, CBG does not have psychoactive effects.
CBG is known to stop growth of bacteria, stimulate bone growth, encourage cell growth, reduce inflammation (CBGA), inhibit cell growth in cancer cells.
For a comprehensive review of CBG’s properties, check out our article Demystifying CBG: The Mother of All Cannabinoids.
Tetrahydrocannabivarin (THCV)
THCV is structurally very similar to THC, as the only difference is having a 3 carbon group instead of a 5 carbon group. THCV is an antagonist at the CB1 receptor and acts as a partial agonist at the CB2 receptor.
THCV may also help with migraines, reducing panic attacks, suppressing hunger, and help with bone growth. THCV may also help with type II diabetes.
The cannabis community has not yet come to a consensus on if THCV is psychoactive or not. Some claim it is not, while others say it provides a short and intense high with a sativa-like effect. Maybe it is not psychoactive on its own, but changes the way THC interacts with our body and mind.
To learn more about THCV, read our article Could THCV Be the Cannabinoid of the Future?
Tetrahydrocannabinolic Acid (THCA)
THCA is the precursor to THC, yet is non-psychoactive. When synthesized in a pure form, it is an unstable powder.
By the time the bud is cultivated, THCA is the predominant cannabinoid present. It doesn’t get turned into THC until it is burned, vaporized, or heated until it gets to a high enough temperature. Its anti-inflammatory properties come from COX-1 and COX-2 enzyme inhibition.
THCA has anti-proliferative, anti-inflammatory, and antispasmodic effects. Also, it may help with chronic immune system disorders, such as Lupus. The anti-inflammatory properties also make THCA great for arthritis, endometriosis, and menstrual cramps.
THCA also may provide users with a burst of energy. The plant has more THCA than the flower, so you can make juice from cannabis leaves to get a product with more THCA.
To read more about the properties of THCA, check out our article THCA: THC’s Non-Psychoactive Sister.
