ThePineapple - How cannabis interacts with the endocannabinoid system, an introduction.

Goldilocks, cannabis and the endocannabinoid system (ECS)

Why cannabis has potential as a medical treatment.

With the recent launch of the James Webb telescope, humanity is on the verge of potentially discovering new habitable planets. Those habitable planets will have one thing in common: they orbit their star at just the right distance. NASA calls that distance the Goldilocks Zone. It is the orbital range within which temperatures are such that life is theoretically possible. Why am I telling you about this? Well, because the concept of the Goldilocks Zone is not only easy to visualize, it applies all the way down to the cells of your body. Just like the planets, your cells need to be maintained within just the right conditions for life to persist. The body’s endocannabinoid system is involved in this maintenance program, and cannabis interacts with this system. In this article, I will use analogies to help you understand the key idea of where the health benefits of cannabis come from.

The Rule of Three

You may have noticed that there is undeniable momentum building towards legalizing cannabis. This movement is a desperate push upward through the state political machinery by the people "illegally" consuming it. At its core, the momentum is driven by three factors:

  1. People looking for relief from their daily psychological and physiological discomforts.
  2. Prolonged cannabis consumption appears to have significantly less of a negative impact on human physiology than other recreational drugs, like tobacco and alcohol. In other words, it seems to be safer. 
  3. The medical industry has corroborated several significant health/medical benefits for many patients with various hard-to-treat chronic ailments.

Fueled by the three factors mentioned above, the legalization of cannabis is a three-step process. 

  1. Decriminalization
  2. Medical use
  3. Adult recreational use (Its final form)

With this repeated pattern of "threes" staring me in the face, I am reminded of the rule of three:   

The rule of three is a writing principle that suggests that a trio of events or characters is more humorous, satisfying, or effective than other numbers. - Thanks, Wikipedia!

One of the most famous pieces of literature employing said rule of three is Goldilocks and the Three Bears. This story is also the perfect analogy for explaining the underlying biological principle of why cannabis is helpful as a medical treatment. You may be familiar with the ancient wisdom of "too much of a good thing is bad," or, "at the wrong dose, everything can be a poison." Indeed, even two of the most essential human life requirements, oxygen and water, can kill us if we either don't get enough or have too much of it.

For optimal function, biological systems require environmental conditions to be just right - the Goldilocks Zone

Similarly, for Goldilocks, the porridge had to have just the right temperature and the bed needed to be just soft enough. Biology is filled with examples of "optimal ranges." Every enzyme in your body requires just the right temperature, salt concentration, and pH to function. This is one reason hypo- or hyperthermia is bad, and you must visit a doctor when you are running a high fever, or if you’ve gone skinny dipping at the north pole. It is also why astronomy and astrobiology refer to the “habitable zone” around a star as the “Goldilocks Zone.” For life, conditions have to be just perfect. Thus NASA is spending a great deal of time searching for planets of just the right size and composition at just the right distance to its star.

Cannabis and the human Goldilocks Zone

The Goldilocks analogy can help us understand why cannabis might assist in managing several chronic diseases. The human body is an interconnected web of complex and calibrated systems that must function in unison for us to keep on keeping on. If a particular system is running beyond its optimal parameters, it is off-balance, and there will be knock-on effects that are sometimes severe. When driving a car with unbalanced wheels the whole thing starts violently vibrating the faster you go. When you take it to the shop and the mechanic adds this tiny piece of metal weight to the wheel, everything runs smoothly again. Biological systems are similar except the balance lies in enzyme activities, stoichiometric substrate concentrations, cytokine levels, cell activity, and many more equally sciencey-sounding things. At their core, it is all about balance and staying within the Goldilocks Zone. 

Imagine a DJ's mixing board with a massive collection of sliders. Each slider represents one of those essential systems, for example, the nervous system or the immune system. When the sliders are centered each system is balanced in a state that is called homeostasis. Each of the sliders has a bit of a buffer, so you can wiggle it around within certain pre-set limits without changing anything. That “wiggle room” is the homeostatic range. If your body needs to orchestrate a response to an invading infection, some sliders need to be tuned up and others need to be tuned down, depending on what kind of infection (virus, bacteria, parasite) it is. After the immune system does its thing for a while, it needs to be deactivated again. Otherwise, it will start inadvertently harming other parts of your tissue as collateral damage. The sliders must be moved back into a neutral position.

The endocannabinoid system (ECS) is involved in returning activated cells back to a neutral resting state

One of the biochemical systems involved in returning those sliders back to neutral is the endocannabinoid system (ECS). The A-ha moment starts here! Our body’s nervous and immune system heavily relies on activation chains. This means one cell activates another that activates the next and so forth. After a while those cells need to be deactivated again and the ECS sends messages backwards along those chains to return them to a resting state or homeostasis. The signals are sent via a class of compounds called endocannabinoids. The "endo" in "endocannabinoid" stands for “endogenous”, meaning that our own body makes those compounds.

As luck would have it, certain plants make compounds that happen to fit into the same receptors as our own endocannabinoids. Because the source of those cannabinoids is a plant, we call them "phytocannabinoids." Cannabis is the plant we’re talking about! Isn't that great? Cannabis contains many hundreds of phytocannabinoids, two of which you may have heard of: THC and CBD. While they can bind to the same receptors as human endocannabinoids, they don't bind with the same strength or the same place on the receptor.

Cannabis derived phytocannabinoids like THC interact with the ECS and can induce homeostasis

For instance, THC can bind to its receptor more strongly. While it can return the sliders back to neutral, it will bind so strongly that it will make the sliders "sticky" for a while. This is important to note because you may need to moderate consumption to keep those sliders moving when you need them. Otherwise, it might cause some complications with other medications you might be taking. 

Homeostasis and disease

Now that you understand homeostasis, we can talk about how chronic disease fits in.  Think about what it means if the sliders on the metaphorical DJ's mixing board don't return all the way back to neutral, and stay just outside of the homeostatic range, or the "buffer/wiggle room" that I described before.

Failure to return cells to a state of homeostasis can result in chronic diseases, like chronic inflammatory or neurological disorders

Let's say the slider represents the motor neurons of a Parkinson's disease patient. Those neurons continuously fire off movement signals to the muscles, causing the signature tremors that make it so hard for people to operate a spoon when they are trying to eat food. Another example could be a neuralgia patient experiencing constant neuropathic pain because their nerves are erroneously sending the pain signal to their brain. In many cases, chronic symptoms and discomfort can be traced to one or more metaphorical “sliders” not returning back to neutral. 

Cannabinoid receptor distribution of the Endocannabinoid System

⁠This ability to interact with your body’s own endocannabinoid system (ECS) is what makes cannabis a potentially useful medical option. Returning cells to a state of homeostasis appears to be the common mechanism that diseases with recorded benefits from cannabis share.  So, while Goldilocks would probably make for a rather fussy Yelp reviewer, I hope her story helps you understand the basics of how cannabis can help manage chronic diseases, and why cannabis legalization is being pushed upward through the states by the medical industry.