THC Tolerance and Chemical Effects

An individual can develop a tolerance to cannabis similarly to that of alcohol, tobacco, and caffeine. Fortunately, cannabis tolerance resets to normal relatively quickly. In cannabis, there are more than 420 chemicals of which 61 are cannabinoids, the most relevant ones being tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD). The most abundant cannabinoid, tetrahydrocannabinolic acid (THCA), is decarboxylated by heat into delta-9-tetrahydrocannabinol (THC).

thc tetrahydrocannabinol

Tetrahydrocannabinol

THCA + HEAT = THC

You can read more about the biochemistry of cannabis in a future post. When discussing tolerance, it is mainly THC that we are concerned with. Before we understand THC tolerance we must first understand the endocannabinoid system (eCB). 

The Endocannabinoid System

The endocannibinoid system (eCB) consists of the cannabis receptors CB1 and CB2, endogenous agonists, and agonist-metabolizing enzymes. In humans, the eCB has regulating roles in hunger, feeding, and energy metabolism; neural plasticity and neuroprotection; autonomic tone, immune response, connective tissue repair, and behavior.

The cannabinoid receptors, which evolved about 600 million years ago, are what the cannabis cannabinoids—like THC, CBN, and CBD—bind to. CB1 is primarily found in the central nervous system, but also appears in the gut, sexual organs, fat, and elsewhere. Interestingly, humans have more CB1 receptors than opioid receptors. On the contrary, CB2 receptors are typically found in the immune system and gastrointestinal system. Endocannabinoids manufactured by our own bodies (called endogenous endocannabinoids) which bind to the CB1 and CB2 receptors, are partly responsible for the runner's high experienced after intense exercise. The endocannabinoids in cannabis also bind to these same receptors.

Here's a decent video giving an overview of the endocannabinoid system for those of you into science or those looking for a more in-depth explanation.

Web: http://ebooks.benthamscience.com/book/9781608050284/ eBook: Endocannabinoids: Molecular, Pharmacological, Behavioral and Clinical Features Author: Eric M.-Rodríguez 

Developing a THC Tolerance

Thus, the more you consume cannabis the more you activate your CB1 and CB2 receptors. If you continually "drown" your endocannabinoid receptors, the regulatory systems of the body start to downregulate the amount of endocannabinoid receptors to maintain equilibrium.

The end effect is that you need more cannabis to achieve the same desired effects as before. Fortunately, even those individuals with the most extreme endocannabinoid downregulation only have to wait for two days of abstinence for the receptor expression to significantly return toward normal.

Tolerance Anecdotes

It has been observed by some people that tolerance has less carry-over between different methods of consumption. This is easily verifiable in edibles where the primary effects are from 11-hydroxy-THC—due to it being processed by the liver—rather than THC. Thus, one may develop a high tolerance for THC from smoking or vaping cannabis that does not necessarily carry-over to the 11-hydroxy-THC from edibles.

Other individuals swear by switching up their method of consumption (from joints to vaping, or vaping to water pipes) from time to time. A final common tip is to switch up the time of the day that you typically consume cannabis. If you primarily consume in the evening hours then a morning session might be a pleasant change.

Forrest Bloom