The cannabis plant contains hundreds of phytocannabinoids, which are natural compounds that can interact with the human body. While not everyone is familiar with the term “phytocannabinoid,” most people have heard of the two main phytocannabinoids in cannabis: cannabidiol (CBD) and tetrahydrocannabinol (THC). Most people are also familiar with the effects of these phytocannabinoids, especially the psychoactive effects of THC. But what about all of the other phytocannabinoids in cannabis? How do they interact with the body?
The science of phytocannabinoids is in its early stages, so our scientific understanding of phytocannabinoids is still evolving. With that said, there’s now phytocannabinoid research that can help us begin to understand how these microscopic compounds may interact with the body. And, below, we’re taking a closer look at this research as we summarize the evolving science of phytocannabinoids. First, we’ll go over the definition of phytocannabinoids and give some vital background information on the human body’s endocannabinoid system. Then, we’ll detail the main phytocannabinoids in cannabis and discuss what science has revealed about each phytocannabinoid.
What are Phytocannabinoids?
Phytocannabinoids are naturally occurring compounds in plants that can interact with the body’s endocannabinoid system. The phytocannabinoids in cannabis plants are more commonly called cannabinoids.
Cannabis plants contain hundreds of cannabinoids, but they aren’t the only plants that contain phytocannabinoids. Beta-caryophyllene, or caryophyllene, is best known as an aromatic terpene, but it has also been identified as a cannabinoid that may have anti-inflammatory and pain-relieving properties. This spicy, peppery smelling compound can be found in numerous plants, including black pepper, cloves, oregano, cinnamon, basil, hops, and cannabis. Other plants appear to contain cannabimimetic compounds, which are compounds that interact with the endocannabinoid system in a similar way to cannabinoids. Examples of plants that contain cannabimimetic compounds include echinacea, kava, liverwort, chocolate, black truffes, and Chinese Rhododendron.
When discussing phytocannabinoids, it’s important to mention the other main type of cannabinoids: endocannabinoids. Endocannabinoids are cannabinoids that are endogenous to the human body. These are a part of the body’s endocannabinoid system, which we’ll go over in the next section.
Understanding the Endocannabinoid System
The endocannabinoid system (ECS) is a nerve cell signaling system that’s found throughout the body. It’s thought that the ECS plays a role in maintaining homeostasis and in the modulation of many nervous system functions, including mood, memory, appetite, and sleep.
There are three parts of the ECS: cannabinoid receptors, endocannabinoids, and enzymes.
Cannabinoid receptors sit on the surface of cells. They can receive messages from the cell itself and from cannabinoids like endocannabinoids and phytocannabinoids.
There are two major cannabinoid receptors:
- CB1 Receptors: These cannabinoid receptors are abundant in the brain and the rest of the central nervous system.
- CB2 Receptors: These cannabinoid receptors exist throughout the body. They’re more abundant outside of the central nervous system in systems such as the immune system.
Endocannabinoids are cannabinoids that are made by the human body as needed. Endocannabinoids act like messengers within the endocannabinoid system. They are ligands that bind to and deliver messages to cannabinoid CB1 and CB2 receptors.
There are two main endocannabinoids:
- Anandamide (AEA): Anandamide, technically known as n-arachidonoylethanolamine, is a fatty acid neurotransmitter that’s also been called “the bliss molecule.” Anandamide is thought to play a role in pain, appetite, depression, memory, and embryo development.
- 2-arachidonoylglycerol (2-AG): 2-AG is a signaling lipid that’s thought to play a role in emotion, cognition, energy, pain, and inflammation.
Enzymes break down endocannabinoids once they’re used within the ECS. There are two main enzymes in the ECS:
- Fatty acid amide hydrolase (FAAH): FAAH breaks down anandamide.
- Monoacylglycerol acid lipase (MAGL): MAGL breaks down 2-AG.
The enzymes in the ECS break down endocannabinoids incredibly quickly. However, they’re less effective at breaking down phytocannabinoids, which allows phytocannabinoids to interact with the ECS for a longer period of time.
List of Cannabinoids in Cannabis Plants
There are hundreds of cannabinoids in the cannabis sativa L. plant, but they’re all offshoots of just two compounds: cannabigerolic acid (CBGA) and cannabigerovarinic acid (CBGVA). All of the other cannabinoids in the cannabis plant are created when these cannabinoid precursors undergo some type of synthesis. The biosynthesis of cannabinoids can occur due to an enzymatic reaction, but more often occurs due to decarboxylation, isomerization, or oxidation.
Some of the cannabinoids in cannabis can be found in the raw plant, while others need to undergo some type of activation or synthesis. The cannabinoids in raw cannabis trichomes are cannabinoid acids. These include CBGA and CBGVA and their derivatives:
- Cannabigerolic acid (CBGA)
- Tetrahydrocannabinolic acid (THCA)
- Cannabidiolic acid (CBDA)
- Cannabichromenic acid (CBCA)
- Cannabigerovarinic acid (CBGVA)
- Tetrahydrocanabivarinic acid (THCVA)
- Cannabidivarinic acid (CBDVA)
- Cannabichromevarinic acid (CBCVA)
Through various types of synthesis, these cannabinoid acids can be transformed into cannabinoid form:
- Cannabigerol (CBG)
- Delta-9-tetrahydrocannabinol (THC)
- Cannabidiol (CBD)
- Cannabichromene (CBC)
- Cannabigerivarin (CBGV)
- Tetrahydrocannabivarin (THCV)
- Cannabidivarin (CBDV)
- Cannabichromevarin (CBCV)
These are some of the more notable cannabinoids in the cannabinoid plant. Some other notable cannabinoids are cannabinol (CBN) and cannabicyclol (CBL), which are degraded forms of THC and CBD, respectively.
The cannabinoids mentioned above are not the only cannabinoids in cannabis, but they are the most well-studied. Let’s go over what science can tell us about each of these phytocannabinoids.
Because CBGA is the precursor for so many cannabinoids, including CBD and THC, cannabigerol (CBG) is known by some who study phytochemistry as the mother of cannabinoids. But CBG is more than just a mother cannabinoid— it also has applications of its own. CBG is able to bind to both CB1 and CB2 receptors, and is thought to have a positive effect on the pleasure and motivation endocannabinoid anandamide.
CBG hasn’t been studied as extensively as some other cannabinoids, but there has been a fair amount of research done on CBG. The current research suggests that CBG could have the following potential benefits and treatment applications:
- Inflammatory Bowel Disease: A 2013 animal study found that CBG had beneficial effects on inflammatory bowel disease in mice.
- Glaucoma: A 2009 animal study found that CBG reduced eye pressure and increased aqueous humor outflow in cats with glaucoma.
- Huntington’s Disease: One 2015 study found that CBG acted as a neuroprotectant in mice with Huntington’s Disease. CBG also appeared to improve motor deficits and protect against 3-nitropropionic acid toxicity.
- Cancer Treatment: A 2014 animal study found that CBG appeared to block receptors that caused cancer cell growth, causing an inhibition of the growth of cancer cells in the colon.
- Antibacterial Properties: A recent study found that CBG had antibacterial properties. Notably, CBG appeared to be especially effective against drug-resistant Staphylococcus aureus (MRSA) bacteria.
Delta-9-tetrahydrocannabinol (THC) is the most well-known cannabinoid in cannabis. THC is famously responsible for marijuana’s psychoactive effects.
Since THC is the most well-known cannabinoid in cannabis, it may come as no surprise that it has been more extensively studied than most other cannabinoids. Scientists have found that THC is a partial agonist that can bind directly to cannabinoid CB1 receptors. This is what causes THC’s psychoactive effects, but research suggests that this also causes other effects, including ones that could ease various health issues.
Research suggests that THC may have the following applications and benefits:
- Pain Relief: Some studies have found that THC may relieve pain, including chronic nerve pain. According to Harvard Health, chronic pain is the top reason for medical marijuana use.
- Nausea Reduction and Appetite Stimulation: Many studies have found that THC can reduce nausea and stimulate the appetite. A synthetic analogue of delta-9-THC, dronabinol, is the active ingredient in Marinol, a prescription drug that’s FDA-approved to treat chemotherapy-induced nausea and vomiting, and appetite loss in AIDS patients.
- Muscle Spasticity: Research shows that THC calms muscle spasticity, including muscle spasticity in marijuana users with multiple sclerosis. It’s thought that spasms originate in areas that have abundant cannabinoid receptors, so some scientists theorize that THC interferes with spasticity signals in the brain.
- Glaucoma: Research shows that THC can reduce intraocular pressure, making it a potential treatment for glaucoma.
- Anxiety and PTSD: Research shows that low doses of THC can have therapeutic effects on anxiety. THC also seems to be a promising potential treatment for PTSD.
Over time, THC gradually breaks down into cannabinol (CBN). This breakdown can occur more quickly when THC is exposed to oxygen and direct sunlight.
CBN is a lesser studied cannabinoid, but it’s commonly observed to have the following properties:
- Psychoactive: Like THC, CBN is psychoactive, but it’s far less so compared to THC.
- Sedative: CBN has a notable sedative effect, which may be greater in combination with THC.
Cannabidiol (CBD) is a well-known cannabinoid that’s found in marijuana plants and cannabis hemp plants. This non-psychoactive cannabinoid is thought to have many health benefits, so it’s become a popular addition to natural products for health and wellness. It’s also the active ingredient in the only FDA-approved prescription medication made from cannabis, Epidiolex.
Alongside THC, CBD is one of the two most extensively studied cannabinoids. Unlike with THC, we don’t yet know how CBD interacts with the endocannabinoid system, as it doesn’t appear to directly interact with either CB1 or CB2 receptors. But while we don’t know the entire pharmacology of CBD, we have a strong initial understanding of the effects it may have on the body.
Studies have shown that CBD may have a vast number of health benefits, including:
- Seizure Treatment: Studies and clinical trials have shown that CBD may help suppress seizures by decreasing brain inflammation, altering calcium levels in the brain, and slowing down seizure-related messages within the brain. The active ingredient in the FDA-approved epilepsy medication Epidiolex is cannabidiol.
- Anti-Inflammatory Properties: Many studies suggest that CBD could have potent anti-inflammatory properties.
- Neuroprotective Properties: Studies have shown that CBD may have neuroprotective properties that could help treat conditions such as Parkinson’s disease, multiple sclerosis, and neuropathic pain.
- Cancer Treatment: Some research suggests that CBD may reduce negative side effects of cancer treatment, such as nausea. A recent review of in vitro and in vivo studies also found that CBD may increase tumor cell death and slow tumor growth.
- Anti-Nausea Properties: Studies have found that CBD eases nausea and vomiting. One study suggests that CBD is able to attenuate vomiting and nausea through indirect agonism of 5-HT1A receptors.
- Psychosis Treatment: Research suggests that CBD may ease psychosis, so some scientists believe it has a potential use in psychiatry.
- Chronic Pain Treatment: Numerous studies have shown that CBD may ease chronic pain. CBD appears to inhibit both inflammatory and neurological pain.
- Anxiety and Sleep Issues: Some studies suggest that CBD may ease anxiety and insomnia.
- Oxidative and Metabolic Stress: Some studies have found that CBD may help ease the negative effects of oxidative stress and metabolic stress on the body.
CBD degrades into cannabicyclol (CBL) after being exposed to oxygen and light. Unfortunately, there has been almost no research done on CBL, so we don’t know the properties of this cannabinoid. Some have suggested that CBL could benefit other cannabinoids via the entourage effect theory, but no studies have been done on this topic. More research is needed to understand the effects of CBL.
Cannabichromene (CBC) doesn’t get as much attention as THC and CBD, but the research on the potential health benefits of CBC has been extremely promising. Studies suggest that CBC may have the following benefits:
- Cancer Treatment: CBC may have the potential to fight cancer. Studies have shown that CBC may inhibit inflammation and tumor growth. Additionally, CBC appears to have a beneficial interaction with the endocannabinoid anandamide, which fights breast cancer in vitro and in vivo. Studies suggest that CBC may inhibit the uptake of anandamide, allowing it to remain in the bloodstream for longer.
- Pain Relief: A 2011 animal study found that CBC had pain relieving and anti-inflammatory properties.
- Brain Health: An animal study showed that CBC had a positive effect on NSPCs, which are essential to healthy brain function.
- Acne Treatment: A 2016 study found that CBC was a powerful inhibitor of acne. The research team found that CBC had anti-inflammatory properties and that it suppressed excessive lipid production in the skin.
Cannabigerivarin (CBGV) is a minor cannabinoid that is understudied. According to the little research we have on CBGV, it’s benefits may include having cancer-fighting properties.
Tetrahydrocannabivarin (THCV) is a natural analog of THC and it’s similar in structure to THC. But THCV has a 3-carbon side chain instead of a 5-carbon side chain, which changes the way it can interact with the ECS. Like THC, THCV is psychoactive, but only in very high doses. Also like THC, THCV has some potential health benefits. While there’s less research on THCV compared to THC, studies suggest that THCV may help manage the symptoms of diabetes and stimulate bone growth.
Cannabidivarin (CBDV) is a minor cannabinoid and a homolog of CBD. CBDV is similar in structure to CBD, but has a side chain that is shooter by two methylene bridges.
Researchers have paid little attention to CBDV. However, some promising studies have shown that it may have anti-epileptic and anticonvulsant properties. As a result, more studies are being done on whether or not CBDV could potentially treat epilepsy.
Cannabichromevarin (CBCV) is a lesser-known propyl cannabinoid and an analog of CBC. While we know the structure of CBCV, little-to-no research has been done on the effects of this cannabinoid. CBD does not appear to be intoxicating, but little is known about this cannabinoid apart from that.
Final Thoughts: Considering the Entourage Effect
Each cannabinoid appears to have its own unique properties and effects on the body. Additionally, some scientists believe that cannabinoids may also affect each other through something called the entourage effect.
The term “entourage effect” was first coined by Shimon Ben-Shabat and Raphael Mechoulam in 1998. The two scientists used this term to describe the synergistic and antagonistic way they observed cannabinoids interacting with each other and other cannabis compounds, such as terpenoids and terpenes. Other scientists have also embraced and studied this concept, including neurologist and pharmacologist Dr. Ethan Russo, who popularized the term.
Though the idea of the entourage effect has been around for over two decades, there has been little research done on the topic. Some evidence for the entourage effect can be seen in other studies, including many that have noted that CBD appears to reduce the negative side effects of THC. But unfortunately for proponents of the entourage effect, cannabinoids have mostly been studied in pure isolation so far, which makes evaluating the entourage effect challenging. For now, we’ll have to wait and see what future research reveals about how cannabinoids interact with the body, as well as whether or not they have an entourage effect when used in concert.