Understanding Cannabis: Making Sense of the Choices

Why different cannabis products produce different effects, and why understanding your own response matters more than you might think.

There's a lot to unravel when trying to understand cannabis.

Its history, cultural significance, legal status and a new commercial market in the data age all contribute to produce an extraordinary amount of information, opinion and often misinformation. But when trying to understand a substance, knowing what it does or how it works is a natural starting point.

How does cannabis actually work?

The main active ingredients in cannabis produce their effects through interactions with receptors in the body. A receptor is a specialised structure, often found on the surface of a cell, that responds to particular chemicals. You can think of it rather like a lock and key that acts as a switch: when a chemical with the appropriate shape interacts with a receptor, it can trigger a response or action within the cell.

This is one of the fundamental ways medicines produce their effects, we use the effect of substances acting on receptors to trigger a physiological process or change that allows treatment. Understanding where receptors are located in the body can help us understand where a drug is likely to act. For example, two particularly important receptors that interact with cannabis are known as CB1 and CB2. CB1 receptors are especially abundant within the nervous system, particularly the brain. Their activation by THC contributes to changes in perception, memory, mood, appetite, coordination and pain processing. CB2 receptors are more strongly associated with immune cells and immune signalling, although both receptor types are distributed more widely throughout the body [1], which can account for some of the other effects people describe with THC.

Of course, I'm simplifying a very complex model, and there's much more to it, even at this level of abstraction. For instance, not every key opens a lock. Some chemicals bind to receptors without activating them. Others may interfere with or modify the effects of other chemicals. The biology quickly becomes considerably more complicated. CBD, for example, interacts with a much broader range of molecular targets and signalling systems. Its effects cannot be explained simply through activation of CB1 or CB2 receptors, and the full range of its activities remains incompletely understood [1].

Cannabis is more than THC and CBD

This is where scientific understanding begins to diverge from some popular perceptions of cannabis.

Cannabis contains a remarkable variety of chemical compounds. Alongside THC and CBD are other cannabinoids, including CBG, CBC, CBN and THCV to name a few. Foreseeably there may be other compounds which produce unrecognised effects that could be specific to variations in processing of the plant, such as the “curing” process or combustion, or specific to individual biology via “biotransformation” within the body.

Cannabis contains a range of variously chemically related substances, “cannabinoids”. There are also numerous non-cannabinoid constituents, including a family of aromatic compounds called terpenes, which contribute to the distinctive smells of different cannabis varieties. Terpenes have attracted considerable interest because of suggestions that they may influence the effects of cannabinoids. There are laboratory findings that support particular biological interactions, but how, and if, these translate reliably into meaningful effects in people remains not clear [2].

The important point is that cannabis isn't a single chemical or a homogenous group of compounds or a single thing. Unlike virtually almost any other medicine, it's a descriptor for a mixture of different substances whose combined activities are still being investigated.

So what do all the different strains mean?

Historically, cannabis varieties developed in different parts of the world, adapting to local environments and being eventually cultivated for different purposes. Over generations, these plants acquired distinctive characteristics, differences in the plants or the chemicals they produce. Some became associated with particular cultural traditions and uses. However, the enormous expansion of commercial cultivation, selective breeding, crossbreeding and hybridization has muddied these distinctions considerably. Cannabis is evolving and is quite different from what it once was.

Interestingly, modern research suggests that the familiar labels indica and sativa may tell us much less about a plant's genetics, or its likely effects, than people commonly assume. A genetic study published in Nature Plants found that commercially labelled indica and sativa samples were not clearly distinguishable across their genomes. Some differences associated with these labels instead appeared to reflect particular terpene profiles [3]. This makes a kind of sense, since indica and sativa are horticultural descriptions (short, bushy plants versus long, skinny plants), and plant morphology is highly environment-related; it’s likely that they also share similar or related underlying physiology. However, this is particularly interesting because terpenes are often credited with producing the distinctive effects attributed to different strains, but the evidence that particular terpene combinations reliably produce predictable or demonstrable psychological or therapeutic effects in humans remains surprisingly limited.

One of the most interesting things about cannabis is just how unpredictable it can be. Research has demonstrated that products sold under the same strain name can contain quite different combinations of chemicals [4]. Even genetically identical plants can develop different chemical profiles depending on how they're grown [5], and remember, there are still further factors like sprays, gathering, drying, curing and packaging to consider that may influence things further still.

That's just on the botanic side, but what this mean for people?

Why is cannabis so unpredictable?

Studies have also shown that different people can respond quite differently to the same dose of THC [6]. An amount that produces relatively mild effects in one person may cause considerable anxiety, altered perception or impairment in another.

The jury is out regarding indica versus sativa in terms of their effects on humans, since the few studies performed that reinforce the classification were ones where people knew what they were given [7, 8], whereas the small number done where individuals didn't know what they were given showed individuals having difficulty distinguishing indica and sativa. So while cannabis strains are often described as having particular properties, such as being relaxing, stimulating or helpful for sleep, these descriptions are much less reliable than we might imagine.

This doesn't mean the differences between cannabis products aren't real. It just means that understanding those differences requires more than knowing the strain name, THC percentage or forming an expectation based on someone else's reported experience.

From pharmacology to medicine

And it's in the individual patient that all these different factors come together.

Cannabis has developed a rich culture of beliefs, traditions and expectations surrounding different strains and their effects. While some of these ideas may have a basis in individual experience, its often poorly supported by objective research, and many are essentially stories that have become beliefs over time.

That's not necessarily harmful in itself, but it can make it harder to understand how a medication is actually affecting you personally. It can distract from the importance of finding a treatment that, for you personally, produces consistent, predictable and useful results.

Become your own expert

There's an understandable appeal in seeking advice from people who describe themselves as cannabis experts, whether through horticultural knowledge, industry experience or more often simply years of personal use, but there are some important things to remember.

·         First, their journey is not your journey: What works wonderfully for someone else may do very little for you or may even produce unwanted effects.

·         Second, cannabis is now a substantial commercial industry. Advice about particular products is rarely independent of some element of commercial interest.

·         Third, without a foundation in fact or testing, there's a limit on what things can be reliably known.

·         Forth, drugs do not exist in a vacuum, interactions with other medications, or conditions as well as social consequences and legal issues have real impact on the individual and are generally not well understood at the level of enthusiasts.

This is a very commercial area, ripe for exploitation by certain types of individuals: it's important to know what is 'known' from what has been evidenced or proven, and have some understanding that any claims can stand on if giving advice.

There is good news, you can become your own expert. By paying attention to the specific effects cannabis produces, how consistently those effects occur, and how they relate to your medical conditions, other medications and everyday life, you can develop a much clearer understanding of whether treatment is actually helping you. That doesn't require recordkeeping or endless notes. Sometimes a small shift in perspective, or a slightly more analytical approach, is all that's needed. If that approach doesn't come naturally, it's something a decent health professional should be able to provide.

Consistency is an important part of this process. It shouldn’t be regarded as restricting your choices. Consistency provides the foundation for understanding your responses, making informed adjustments and developing treatment that produces sustainable benefits. And that, more than anything else, is the purpose of “medical” cannabis treatment. It’s an intensely practical and personal goal, one that should involve the patient as much as the professional.

Too much of contemporary medicinal cannabis prescribing remains focused on access to products rather than treatment or outcomes. If cannabis, or the reasons you use it, are important to you, reflect that in your choices and actions. And if you need treatment for a medical problem, you deserve to be actually “treated”, not simply sold a product.

References

1. Lu HC, Mackie K. (2016). An Introduction to the Endogenous Cannabinoid System. Biological Psychiatry, 79(7), 516–525. https://doi.org/10.1016/j.biopsych.2015.07.028

2. Russo EB. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344–1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x

3. Watts S, et al. (2021). Cannabis labelling is associated with genetic variation in terpene synthase genes. Nature Plants, 7, 1330–1334. https://doi.org/10.1038/s41477-021-01003-y

4. Smith CJ, Vergara D, Keegan B, Jikomes N. (2022). The phytochemical diversity of commercial Cannabis in the United States. PLOS ONE, 17(5), e0267498. https://doi.org/10.1371/journal.pone.0267498

5. Zandkarimi F, et al. (2023). Comparison of the Cannabinoid and Terpene Profiles in Commercial Cannabis from Natural and Artificial Cultivation. Molecules, 28(2), 833. https://doi.org/10.3390/molecules28020833

6. Atakan Z, et al. (2013). Cannabis affects people differently: inter-subject variation in the psychotogenic effects of Δ9-tetrahydrocannabinol. Psychological Medicine, 43(6), 1255–1267. https://doi.org/10.1017/S0033291712001924

7. Sholler DJ, et al. (2022). Use Patterns, Beliefs, Experiences, and Behavioral Economic Demand of Indica and Sativa Cannabis: A Cross-Sectional Survey of Cannabis Users. Experimental and Clinical Psychopharmacology, 30(5), 575–583. https://doi.org/10.1037/pha0000462

8. Okey SA, et al. (2023). An Ecological Examination of Indica Versus Sativa and Primary Terpenes on the Subjective Effects of Smoked Cannabis: A Preliminary Investigation. Cannabis and Cannabinoid Research, 8(5), 857–866. https://doi.org/10.1089/can.2022.0213