A cannabinoid produced in trichomes of the cannabis plant. When derived from the plant and consumed, phytocannabinoids interact with our body’s receptors to produce numerous psychotropic and therapeutic effects. Both plants and animals produce their own cannabinoids, those produced inside the mammalian body are called endocannabinoids.
“How many different phytocannabinoids are found in the cannabis plant?”
“The effects you’re looking for depend on which phytocannabinoids and terpenes are prominent in this strain.”
More About Phytocannabinoids
What are Phytocannabinoids?
Cannabinoids are a class of lipophilic molecules that interact with the body’s endocannabinoid system (ECS). Phytocannabinoids, or exogenous cannabinoids, are plant-derived cannabinoids produced by glandular trichomes covering the surface of the cannabis plant. Trichomes are responsible for producing all of the plant’s desirable compounds. More than 100 cannabinoids have been discovered in the cannabis plant, though research into their effects has only been done on the most prominent ones. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are not only the most well-known, but also the most prominent phytocannabinoids.
How Do They Differ from Endocannabinoids?
Endogenous cannabinoids, or endocannabinoids, are cannabinoids produced inside the body. Every function in our bodies requires a specific balance of factors in order to perform at maximum capacity. When this balance is achieved, it’s called homeostasis. Endocannabinoids play a major role in survival by helping the body maintain homeostasis.
Because our bodies already use cannabinoid molecules to regulate many functions, we’re inherently endowed with many targets the cannabis plant can activate. Endocannabinoids and phytocannabinoids aren’t necessarily different on a structural level. They both activate the body’s ECS by binding to cannabinoid receptors. Endocannabinoids activate a homeostatic effect, bringing the body to a balanced state of health. They are produced by our cells in an “on-demand” fashion. Phytocannabinoids have the ability to produce more overtly medicinal effects, and may be making up for endocannabinoid deficiencies in the body when they trigger therapeutic responses. Phytocannabinoids are also capable of producing intoxication, which endocannabinoids alone cannot do.
Why Does the Plant Produce Cannabinoids?
The human body produces cannabinoids for survival through the activation of homeostasis. The cannabis plant also produces cannabinoids for survival, but in a far more direct response to external pressures. As they’re produced by the cannabis plant’s trichomes, phytocannabinoids cover the surface of the plant as a defense against environmental hazards such as insect predators and strenuous weather conditions.
Cannabinoids are produced through biosynthesis, in which enzymes trigger a series of chemical reactions that take simple molecules and create more complex ones from those molecules. The enzymes responsible for producing the cannabinoids with which most of us are familiar are cannabidiolic acid (CBDA) synthase, cannabichromenic acid (CBCA) synthase, and tetrahydrocannabinolic acid (THCA) synthase. These enzymes take the central cannabinoid precursors, cannabigerovarin acid (CBGVA) and cannabigerolic acid (CBGA), and convert them into acidic cannabinoids such as THCA and CBDA.
[IMG Cannabis in a pot, over a stove]
From here, these cannabinoids may be altered further through decarboxylation. When a chemical compound decarboxylates, it loses carbon atoms and releases carbon dioxide, either by heat or prolonged overexposure to environmental stress. THCA and CBDA decarboxylate into THC and CBD, respectively, and must do so to exhibit psychoactive effects. THC, CBD, and other neutral cannabinoids can then be metabolized, or broken down into other cannabinoids by way of oxidation, or exposure to oxygen. CBD, for example, may be oxidized into the metabolites cannabielsoin (CBE) and cannabidinodiol (CBND).
How Phytocannabinoids Interact with the Endocannabinoid System
The ECS helps the body maintain functional balance through its three main components: “messenger” molecules that our bodies synthesize, the receptors these molecules bind to, and the enzymes that break them down. Pain, stress, appetite, energy metabolism, cardiovascular function, reward and motivation, reproduction, and sleep are just a few of the functions the endogenous cannabinoid system is involved in.
Cannabinoid receptors fall into one of two categories: CB1 and CB2. CB1 receptors are largely found in the central nervous system, where they regulate a wide variety of brain functions. In fact, they’re the most widely expressed protein of their kind in the brain. The major role of the CB1 receptor is to control the timing and frequency of the release of other neurotransmitters, such as serotonin, dopamine, and glutamate. CB2 receptors are mostly found on immune cells, which circulate throughout the body and brain via the bloodstream. They’re also found on neurons in a few select brain regions. CB2 receptors are involved in pain relief, anti-inflammation, and neuroprotection. Phytocannabinoids interact with the ECS by binding to these receptors, which in turn elicits a regulatory response from the body.
Everyone’s endocannabinoid system is unique. The rates of endocannabinoid production vary wildly, as do the levels of cannabinoid receptors in our bodies. Prolonged use of cannabis causes the brain to reduce the number of CB1 receptors that are available for activation. Using human brain imaging, we can observe that just 48 hours of abstinence from cannabis is sufficient to resensitize the system and bring the expression of CB1 proteins to a level that is comparable to a non-cannabis user.
The Entourage/Ensemble Effect
Cannabis contains hundreds of molecules that have the ability to interact with our bodies and minds directly. Cannabinoid molecules are relatively unique to the cannabis plant, but other plant-derived molecules such as flavonoids and terpenes also bind to our cells and influence our experiences. All of these cannabis-derived molecules work synergistically with one another, potentially enhancing the most desirable effects. Terpenes, for instance, have become an essential piece of the cannabis puzzle because of their potential for supporting, if not outright enhancing, the therapeutic potency of cannabinoids such as THC and CBD. This potentiated relationship between cannabis compounds is known as the entourage, or ensemble, effect.
The term entourage effect was coined by Israeli researcher Dr. Raphael Mechoulam to explain how a combination of cannabis compounds is more effective than an isolated compound. More recently, the term ensemble effect has been used as an arguably more accurate description of the way phytocannabinoids, terpenes, and other cannabis compounds work together cooperatively, rather than one type of cannabinoid leading the charge while the rest follow, as the word entourage implies.
Prominent Phytocannabinoids and Their Potential Health Benefits
As an activator of the CB1 receptor, delta-9-tetrahydrocannabinol — most commonly known as THC — is the main intoxicating component of cannabis. THC intoxication has been shown to increase blood flow to the prefrontal cortex, the region of the brain responsible for decision-making, attention, motor skills, and other executive functions. The exact nature of THC’s effects on these functions will vary from person to person. When THC binds to CB1 receptors in the brain’s reward system, it can trigger feelings of euphoria. Much of THC’s ability to relieve pain is due to its interaction with CB1 receptors in the midbrain.
Tetrahydrocannabinolic acid (THCA) is the most common cannabinoid found in the raw cannabis plant. THCA is non-intoxicating but converts into the intoxicating THC when decarboxylated (by heat). Though far less well-known or commonly used for medicinal purposes than THC, THCA has its own potential in anti-inflammatory, neuroprotective, and anti-emetic treatments.
Cannabidiol (CBD) is the second-most abundant cannabinoid in the plant, and has many potential therapeutic benefits, including anti-inflammatory, analgesic, anti-anxiety, and seizure-suppressant properties. Cannabidiol can be sourced from both marijuana plants and hemp plants.
Cannabidiolic acid is the natural precursor to CBD, and turns into CBD through decarboxylation (heating). If you’re juicing with raw cannabis or consuming the plant in any other raw form, you’ll be ingesting CBDA and not CBD. The effects of CBDA are still being investigated by scientists, however animal studies suggest that it could be an effective anti-tumor, anti-nausea, and anti-inflammatory agent.
Cannabidivarin (CBDV) is a relative cannabinoid of CBD; both derive from the cannabinoid precursor CBGVA. CBDV has been found to have antiepileptic and anticonvulsant properties.
Cannabidivarinic acid (CBDVA) is the acidic form of CBDV found in raw cannabis.
Cannabigerol (CBG) is a decarboxylated form of CBGA. CBG weakly binds to both CB1 and CB2 receptors, and it also inhibits the endogenous cannabinoid anandamide. CBG is currently being investigated for its potential to stimulate appetite, treat Huntington’s, and irritable bowel disease, among other health benefits.
Cannabinol (CBN) is a degraded form of THC, commonly found in old or aging cannabis. CBN remains primarily referenced as a potent sleep aid, though research has not shown such results in humans. It has, however, been found to have potential pain relief, anti-bacterial, anti-inflammatory, anti-convulsant, bone cell growth stimulant, and appetite stimulant properties.
Tetrahydrocannabivarin (THCV) is typically only found in cannabis in trace amounts, but it may contribute to the antiepileptic and anticonvulsant effects of cannabis. Although research is still ongoing, THCV may be useful in treating obesity.
Tetrahydrocannabivaric acid (THCVA) is the acidic form of THCV. More research is needed to fully understand its potential effects.
As the name suggests, delta-8-THC is a close relative of the more prominent delta-9-THC. It only differs from delta-9-THC by the placement of one atomic double bond. More research is needed to discern the exact differences in effect between delta-8-THC and the more prominent delta-9, but early studies indicate that it may be less intoxicating.
There is a staggering number of chemical phenotypes, or chemotypes, of cannabis out there. A cannabis chemotype represents the chemical profile of a cannabis plant, i.e., its cannabinoid and terpene content.
Chemotypes of Cultivated Varieties
Virtually all cultivars are predominant in either THC or CBD, or both. Selective breeding has led to the expression of predominantly THC and CBD in most cultivars. However, research into the chemotypes of today’s cultivars suggests that one cultivated variety does not necessarily express one unifying chemotype, but rather, may exhibit a spectrum of chemotypes. In other words, two plants of the same cultivated variety may have slightly different chemical expressions. A recent study on cannabinoid and terpene expressions in a wide range of plant samples concluded that a chemotaxonomic classification — or, more accurately, classifying cannabis by its cannabinoid and terpene contents — will be more effective than our current Indica/Sativa/Hybrid taxonomy in identifying the best medical uses for a given cultivar.
Chemotypes of landrace varieties
A landrace is a cannabis plant grown in its native environment and geographical region. Acapulco Gold, Panama Red, Afghanistan, and Durban Poison are thought to be examples of original landrace strains of cannabis domesticated for traditional cultivation. The cannabinoid profiles of these landraces represent an approximation of the cannabinoid profiles that nature intended before humans intervened with intensive breeding. Some landrace (or wild-type) subspecies of cannabis are thought to have produced low amounts of THC, whereas other subspecies may have produced high levels of THC.
Concentrates have taken the cannabis world by storm in recent years. Cannabis concentrates isolate and accumulate all of the most desirable properties from cannabis trichomes — namely cannabinoids and terpenes — into one product. You may have either heard of or used full-spectrum extracts, sauce, or distillate. All of these are forms of cannabis concentrates.
Isolates, or extractions of a single phytocannabinoid or terpene, have also become more prominent in the arena of natural medicine. THCA crystalline, for example, has become a popular cannabis isolate of recent years. Crystalline and other cannabinoid isolates are pure concentrations of a single cannabinoid, and as a result may not be as potent as an extract with a full spectrum of cannabis compounds. Without terpenes and other compounds in the mix, there is no potential to benefit from the ensemble effect.
Infused Into Cannabis Goods
Thanks to advances in the cannabis culinary arts and the emergence of distillate, you can find a wide selection of high-quality baked goods, beverages, and treats infused with cannabis flower or concentrate. Consuming cannabis-infused edibles is easy and intuitive, offering the effects of phytocannabinoids and other cannabis compounds without having to smoke or vaporize them.
Edibles are absorbed through the digestive system, which results in delayed onset as compared to inhalation and sublingual delivery. The absorbed compounds are metabolized in the liver. THC is metabolized in the liver into a compound called 11-hydroxy-THC, which is more potent and typically more sedating than THC. Absorbing phytocannabinoids through the liver causes edibles to have their own distinct effect in most people. The onset process can take between 45 and 180 minutes, while the duration of the effects can vary.
Cannabis tinctures — concentrated extracts contained in a liquid, most commonly alcohol or glycerin — came to prominence as a medicine in the mid-to-late 19th century, when western medicine adopted the use of medical cannabis. During the 1890s in particular, medical cannabis reached its peak in Europe, the U.K., and the U.S., largely in the form of extracts and tinctures.
Tinctures are making a comeback following legalization in many parts of the world due to the ability of users to administer consistent doses — the same reason they were popular in the 19th century. Sublingual sprays and capsules have emerged as popular forms of ingesting tinctures.
Topicals are cannabis-infused products applied to the skin in the form of lotions, oils, patches, sprays, soaps, lubricants, bath salts, and cool or warm balms. Topicals allow cannabinoids to be absorbed into the bloodstream at a slower rate than if cannabis were smoked or eaten, so their effects are typically felt only where they’re applied, without the type of stimulation that causes intoxication. Topicals include lotions, salves, oils, patches, sprays, soaps, lubricants, bath salts, and cool or warm balms — and are often made from essential oils and other organic materials.