For years, it was thought that cannabis was the only plant capable of producing cannabinoids. However, in the last few years research has been published that shows that cannabis is not the only plant that produces these compounds. In fact, they are actually quite common!
Cannabinoids are lipid-based molecules that all act to some degree on the cannabinoid receptors, which are a primary component of the endocannabinoid system (EC system). Cannabinoids are produced by plants (most famously, the cannabis plant), but are also produced by the human body and most other animal species. It can also be synthesized in laboratories.
Most cannabis enthusiasts are familiar with the classic cannabinoids such as THC, CBD, THCV and CBC, which for many years were thought to be the only compounds that acted on the cannabinoid receptors. These classic cannabinoids all share the same chemical formula, C21H30O2.
As our understanding of the endocannabinoid system has grown though, we have found that the number and type of different compounds that act on the receptors is much larger than we thought.
Thus, we have to widen the goalposts somewhat as to what constitutes a cannabinoid. Beyond the 120 or so classic phytocannabinoids, there are also an as-yet-undetermined number of related compounds, which also act on the receptors but do not share the classic structure.
What are cannabimimetics?
As well as cannabinoids, we also have an important class of non-classical cannabinoids known as cannabimimetics. They are called cannabimimetics, as they literally mimic the biological activity of the classical cannabinoids, despite not sharing their structure.
Cannabimimetics are of increasing importance within the world of medicinal cannabinoid research. The EC system has traditionally been viewed as a simple set of two receptors and two ligands (a ligand is a compound that binds to a receptor).
However, it is now increasingly being shown that the EC system is far more complex than this. Dozens of different compounds are now known to act either directly or indirectly on the EC system, and many of these compounds also work on other important biological messaging systems such as the opioid, serotonergic and dopaminergic signalling systems.
Some examples of known cannabimimetics:
NAE’s & N-alkylamides
N–acylethanolamines are a class of fatty acid compounds which are known to be heavily involved in biological signaling. NAE’s include N-arachidonoylethanolamine (better known as anandamide), N-palmitoylethanolamine (PEA), N-linoleoylethanolamide (LEA) and N-oleoylethanolamine (OEA).
Anandamide is known for being the biological compound which most closely resembles the activity of THC, as it directly agonizes the principal cannabinoid receptors. It is now known that anandamide minimally agonizes a third cannabinoid receptor known as GPR119 too, which is also affected by N-oleoylethanolamine.
As well as directly acting on the principal and minor cannabinoid receptors, NAE’s are also known to exert a range of indirect effects. For example, LEA, PEA and OEA all inhibit levels of the FAAH enzyme that is responsible for degrading anandamide itself, and thus can effectively increase levels of anandamide in tissues over time.
N-alkylamides are a similar but less well-researched class of cannabimimetic compounds. They have been shown to exert selective effects on the CB2-receptors and anti-inflammatory effects similar to anandamide.
This important terpene is found in cannabis, and its oxide (which forms on contact with air) is one of the compounds detected by drug-sniffing dogs! B-caryophyllene has been shown to act as a full agonist of the CB2-receptor, although it does not act on the CB1-receptor.
It has also been shown to exert anti-inflammatory and analgesic effects in mice, but not in mice bred to lack CB2-receptors. This shows that the biological activity is exerted via the receptors themselves.
Salvinorin A is the main component of the psychoactive plant species Salvia divinorum. Unusual for a hallucinogenic plant compound, salvinorin A is a terpenoid, not an alkaloid like mescaline, psilocybin and DMT. Furthermore, it is a dissociative, rather than a classic hallucinogen.
Interestingly, it seems that Salvinorin A does not interact with the classic cannabinoid receptors. In fact, it interacts with a putative third cannabinoid receptor that apparently forms only in inflammatory conditions, and which also acts as a kappa-opioid receptor. The κ-opioid receptors are fundamental to pain regulation and are also the principal target of most hallucinatory compounds.
Another very important terpene found in cannabis and one that is also a major constituent of the essential oil of hops. Although it is not thought that myrcene directly acts on the cannabinoid receptors, it is now known that myrcene is a prominent sedative terpenoid in cannabis, and combined with THC, may produce the ‘couch‐lock’ phenomenon.
Myrcene is known to be present in high levels in strains that exert a ‘stoney’ or ‘couchlock’ effect on the user. The sedative effects of myrcene-containing plants such as hops and verbena have been known for millennia, and it is now thought that the sedative effect is due to myrcene’s ability to agonise (activate) the opioid receptors.
Thus, although myrcene is not typically classed as a cannabinoid in the current scientific literature, it certainly affects the subjective experience of a cannabis high. Further research will no doubt determine the exact nature of the link; presently, while testing labs such as Steep Hill Halent in California have been collecting data on the association for years, no formal studies have yet been conducted.
Plants that produce ‘cannabimimetic’ compounds
First off, there are abundant plant sources of terpenes such as β-caryophyllene and myrcene. Of course, some sources are better than others. Myrcene is found in extremely high concentrations in hop oil, making up to about 75% of the extracted volume in some varieties, and is also found in high levels in mangoes, lemongrass, thyme and verbena.
B-caryophyllene is found in black pepper, cloves, rosemary, hops, caraway, oregano, basil, lavender, cinnamon, and many more plant species. In most of these species, β-caryophyllene is a major constituent of the essential oil.
Salvinorin A is much rarer and appears to only be found in high quantities in Salvia Divinorum itself. However, there are indications that other sage species may also contain traces of the compound itself, or closely related molecules.
NAE’s including OAE, PEA and LEA have been found to occur in many plant species. Notably, OAE and LEA have both been found in the cocoa plant, and black truffles have even been reported to contain anandamide itself!
Lastly, the compounds known as N-alkylamides have been found in various echinacea species, and it is thought that echinacea’s importance in herbal medicine may derive from this fact.
In time, the list of plants that can safely be said to contain cannabimimetic compounds will no doubt expand, as we continue to find compounds capable of acting on the EC system.
But do any plants produce classical cannabinoids, other than cannabis?
Up until very recently, it seemed that the cannabis plant was unique in producing the true, classic cannabinoids. However, this conventional wisdom appears to have been turned on its head with the discovery in 2012 that flax (linen) seeds seem to produce cannabidiol (CBD)! Or at least, that they produce cannabinoid-like compounds very similar to CBD, which appear to have similar anti-inflammatory effects.
Earlier research suggests that the compound cannabigerol (CBG) and its precursor cannabigerolic acid (CBGA) are present in a South African herb. A more recent (2011) study suggests that cannabichromene (CBC) and some related compounds are also present in Chinese rhododendron.
Lastly, there is even a plant known as the New Zealand liverwort, which produces an unusual type of cannabinoid (called perrottetinenic acid) that appears to be very closely related to THC. It may actually act on the CB1-receptor! If this is the case, it will be the only other known plant compound found in nature that is capable of doing so. However, whether or not this compound actually acts on the CB1-receptor is not yet definitively known.
And one thing we seem to know for sure: no other plant aside from cannabis produces THC.
- Disclaimer:This article is not a substitute for professional medical advice, diagnosis, or treatment. Always consult with your doctor or other licensed medical professional. Do not delay seeking medical advice or disregard medical advice due to something you have read on this website.