By John Brunstein
26 Apr 2016
What exactly is THC and CBD and how does it effect our bodies? I hear people talk about it all the time when describing certain kinds of Cannabis. NP
NP, there’s without exaggeration several thousands of pages of published research information relating to these questions – and in the case of the second one, they don’t even always agree completely with each other. Bear in mind that the brief answer I will provide here is thus very much summarized, and will generalize over many of the nuances and complexities still being studied in this topic to just cover some of the main points as we understand them currently.
What they are is easier to describe. The Cannibaceae family of plants produce a unique set of intermediary metabolites known as the cannabinoids. There are actually quite a lot of different molecules which fall under this umbrella (more than 80, perhaps more than 100 depending on what data you take as being correct). Most of these are only present in trace amounts though as metabolic intermediates, with THC (Δ-9-tetrahydrocannabinol) and CBD (cannabidiol) being the two exceptions and major end products of the pathway. One or the other of these (or a mixture of the two) can reliably be present in relatively high concentrations in “drug-type” cultivars or strains. Cannabinoids are also detectable in hemp or “fibre-type” cultivars, but on the order of 100-fold lower concentrations. We’re not sure what the purpose of the cannabinoids is exactly in the Cannabis plant, but one suggestion is that they act as part of the plant’s defense mechanism against microbial pathogens and as signalling molecules involved in programmed plant cell death as a part of development .
The structures of THC and CBD are shown in Figures 1 and 2, respectively.
Figure 1: THC
Figure 2: CBD
As you can see when they’re shown next to each other, they’re very similar molecules. It’s believed they are synthesized from a common precursor (cannabigerol, or “CBG”, one of those low-abundance intermediates mentioned above). A somewhat simplified summary of current thinking is that after CBG is synthesized, it acts as a substrate for an enzyme coded for at the THC synthase locus of the Cannabis genome. Like humans, Cannabis plants have a diploid or two-copy genome, meaning there are two copies of this gene location. There’s more than one form of this gene, though – one form “THC synthase” turns CBG into THC, and another form “CBD synthase” turns CBG into CBD. (There are almost certainly nuances or variations on each of these forms, with slightly different properties such as speed of action; and possibly other separate enzyme type, but for this discussion we’ll just simplify this to these two). Since there are two gene locations, and two possible gene forms, you can have three total genetic results. (Four if you’re a mathematician, but two are indistinguishable, so three net forms). One has two copies of THC synthase, and thus makes almost all CBG into THC; this is a high-THC strain. The second possible genotype is one copy each of THC synthase and CBD synthase, which would then make both THC and CBD; one enzyme is probably a bit faster or more efficient than the other, so it’s not exactly a 50:50% split, but the strain clearly makes both CBD and THC. The third possible genotype has both copies as CBD synthase, so it will turn almost all of the CBG into CBD; this is a high-CBD strain. If now you’re wondering why you don’t see exactly 100% THC/0% CBD or vice versa on product analyses data, it’s because each of these enzymes makes at least a tiny bit of the other product.
Our interest in these molecules stems from their physiological activities in humans. As we currently understand it, these effects arise through chance as much as anything. Humans (and in fact, most higher mammals) turn out to have a complex cellular signalling system based on lipid-derived signalling molecules covering a number of quite unrelated functions. Due to its responsiveness to cannabinoids, these are known as the endocannabinoid pathways and have two major signal receptor types known as the CB1 and CB2 receptors. CB1 receptors are most prevalent in certain brain areas but occur in lower numbers in many other organs of the body, while CB2 receptors mostly are found associated with immune system cells (see for instance ). This starts to hint at the answer to your second question, because despite their similar structural appearances, THC and CBD interact with these receptors quite differently .
THC binds to and activates both CB-1 and CB-2 receptors. Simplistically, this binding to CB-1 receptors underlies the psychoactive effects of Cannabis by altering the body’s natural neurotransmission by CB-1 containing neurons. Active CB-1 receptors work to inhibit the release of yet other neurotransmitters, so in some cases this action by THC may help to suppress overactive neurons with a calming or sedative effect. The brain is a complex system though and in other neurons, CB-1 activation can lead to an enhanced signal as opposed to a suppressed signal; an example of this second type is the appetite enhancement associated with Cannabis use via increased activity in hypothalamic pro-opiomelanocortin (POMC) neurons . This complexity is why THC (and thus Cannabis use in general) effects can be different in different people and even sometimes in different situations. The basic take home message though is that THC is what’s responsible for sensory (psychoactive) effects of Cannabis, from a “high” to sedation, pain suppression, and other less common effects.
Figure 3: The human brain is complex system.
CBD on the other hand has very poor binding affinity for both the CB1 and CB2 receptors. What it does do, is interfere with other molecules (endogenous cannabinoids) binding to these receptors . It also appears to bind and activate what’s called by the uncomfortably long name of “transient receptor potential vanilloid type 1” or TRPV1, which is involved in pain perception. On the whole, CBD acts to have anti-inflammatory, analgesic (pain reduction), and antispasmodic or seizure reducing activity. If you’re familiar with the well publicized stories of Cannabis or Cannabis extracts being used very successfully for the reduction of epileptic seizures in children, CBD appears to be the cannabinoid responsible. As you can imagine, a compound without psychoactive properties, and with ability to reduce pain, inflammation, and suppress epileptic seizures, sounds like it would have a great many medical uses. A lot of exciting active research is being done on CBD for exactly that reason, and it’s for these sorts of possible medical applications that some Cannabis producers already include high CBD, low THC strains in their crops. (Recall above, we examined how if you had a strain which had duplicate copies of the CBD synthase allele and lacked the THC synthase allele, you’d have a strain which would mostly produce CBD).
By the way, if you look into CBD further, you come across claims that it acts by inhibiting (blocking or slow down) an enzyme called fatty acyl amide hydrolase (FAAH), which is what breaks down endogenous cannabinoids; so CBD should in theory help keep these endogenous cannabinoids at higher levels and signalling longer than they would be if they were being degraded at full speed by FAAH. That turns out to be a great theory in rats but not in people – a recent study has shown that human FAAH isn’t inhibited by CBD and so this explanation may not be valid .
At this point you may start to have a feel for what THC and CBD are and do, but even a brief discussion wouldn’t be complete without bringing up what’s referred to as the ‘entourage effect’. Note from above how THC binds CB1 and CB2, and CBD basically doesn’t, but can change how other molecules (including THC) do bind these receptors. In other words, THC and CBD can interact with each other in a sort of molecular balancing act. The term ‘entourage effect’ is used to summarize this observation that there are synergistic effects between CBD and THC, and what can be important is the ratio of one to the other in determining the overall effect of a Cannabis-based medicine. Remember all those other, not very common cannabinoids? Well, it turns out at least some of them may too – even at very low levels – play a role in modulating the physiological effects of THC and CBD. Because small changes in genetics between Cannabis strains may impact the relative levels of all of these many other cannabinoids, two products with similar THC and CBD levels may not have the exact same effect on a user. That’s part of why there’s such a diversity of Cannabis strains available (someone may have to try several seemingly similar ones to find the one which works best for them and their specific condition). It’s also part of why Segra is investing heavily in Cannabis genotyping. We need to be sure that our strains remain uniform over time, without genetic drift leading to unwanted changes in the ‘other’ cannabinoids which can hide behind unchanging THC:CBD values and ratios.
The briefest summary then comes down to a few points:
1: Shoyama Y., Sugawa C., Tanaka H., and Morimoto S. Cannabinoids act as necrosis-inducing factors in Cannabis sativa. Plant Signal Behav. 2008 Dec; 3(12): 1111–1112.
2: Mackie K. Cannabinoid receptors: where they are and what they do. J Neuroendocrinol. 2008 May;20 Suppl 1:10-4.
3: Pertwee R G. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Brit. J Pharm. 2008 Jan; 153(2): 199-215
4: Koch M et. al. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature. 2015 March; 519
5: Elmes et. al. Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). J Biol Chem. 2015 Apr 3;290(14):8711-21.