How Cannabinoid Receptor Density Determines Personality

In From Bud to Brain, I traced how marijuana research gradually morphed from focusing on the cannabis plant (botany) to exploring the brain’s natural endocannabinoid system (neuroscience) and, incidentally, how it interacts with the cannabis plant’s chemistry. Without an understanding of this endocannabinoid system, it is impossible to explain how THC and CBD ingestion produces pleasant effects for so many people, why too frequent use of cannabis can produce subtle cognitive and emotional impairments, and how selective use of cannabis has medicinal benefits for a variety of illnesses. The shift to pure neuroscientific research focused on our natural cannabinoid chemistry is nicely illustrated by Koen Van Laere’s discovery of how genetic variations in the density of active CB1 receptors determine temperamental traits of extroversion, with its novelty-seeking [1] and increased risk-taking [2], and introversion’s novelty and risk avoidance.

Temperament refers to stable biological traits such as biorhythms, emotional reactivity, and introversion/extroversion. Temperament is genetically determined and should not be conflated with personality. Two individuals with the same temperamental trait of novelty-seeking can incorporate this trait into destructive personalities, with one becoming an inveterate world traveler while the other becomes ensnared in a series of drug addictions.

Our amygdala generates the experience of novelty. Karl Pribram, with whom I did a fellowship following my psychiatric training, described in Languages of the Brain how the amygdala monitors current stimuli and continually compares them to recent stimuli. When a change is detected, such as a refrigerator motor’s turning off, the amygdala sends a signal to the hippocampus to alert it to the changed stimulus. This “zing” sent to the hippocampus is experienced as novelty. The bar for the amygdala’s noticing a large enough change to initiate novelty is set by the level of activity in its endocannabinoid system. Ingesting THC increases endocannabinoid system activity, which lowers the bar for experiencing novelty and can lead to dishabituation of stimuli long left unnoticed. Now stoned individuals may notice the rainbow on each bubble in soap suds they had habituated to early in childhood. The world becomes more fascinating. But, when endocannabinoid activity falls below normal physiologic levels, often caused by too frequent cannabis use, the bar for experiencing novelty is set higher than normal and boredom is experienced. High cannabinoid activity produces novelty; low cannabinoid activity reduces novelty.

We now have the background for understanding Van Laere’s discovery that the degree of novelty-seeking is dependent on CB1 receptor density in the amygdala. There are genetic variations in the density of active CB1 receptors, with low baseline CB1 receptor activity leading to high novelty-seeking. Boredom exists without frequent novelty stimulation. As a result, people born with low CB1 receptor activity are relatively unrestrained in their novelty-seeking. Their amygdala responds less, leading them to seek greater levels of novelty to make life interesting.

On the other hand, people born with a higher density of CB1 receptors are more constrained in their pursuit of novelty. The greater responsiveness of their amygdala to novel stimuli leads them to withdraw from too much novel stimulation to avoid being overwhelmed. Neither constrained nor unconstrained temperament is better than the other. Each merely confers different talents and challenges on individuals.

Van Laere’s research has nothing to do with the cannabis plant. It is pure neuroscience. However, Laere’s discovery may give important clues to why some people gravitate toward using cannabis while others are rendered more anxious, and even paranoid, by smoking weed. Low CB1 receptor individuals may welcome the increased amygdala endocannabinoid system activity produced by THC because it brightens their interest in the world. High CB1 receptor individuals, who are already near saturation with novelty, might find the extra endocannabinoid activity in their amygdala disorienting and overwhelming enough to produce anxiety.

Van Laere’s work may also help explain why the 20% reduction in CB1 receptors in the amygdala caused by regular cannabis use^[3],[4], called downregulation, might lead to changes in temperament, and ultimately personality. Individuals with low CB1 receptor density, when not under the influence of regular cannabis use, and because of even further lessening of CB1 receptor density due to downregulation, might become more profoundly bored, unmotivated, and even more desirous in cannabis use. On the other hand, individuals with high CB1 receptor density might, if they use cannabis sufficiently often to downregulate their baseline endocannabinoid system activity, find themselves less constrained when not stoned, until their CB1 receptors return to their normal high level. All this is speculation because controlled experimentation of these phenomenon would be unethical and results of the natural experimentation taking place in the general public are very difficult to reliably disentangle. Nevertheless, anecdotes from significant others strongly suggest regular cannabis use is often associated with a variety of personality changes.

To assess your general knowledge about cannabis, see Test Your Science Literacy About Cannabis.

To assess whether you use cannabis frequently enough to downregulate your CB1 receptors, see 20 Questions to Tell If You're Using Cannabis Safely.