There currently exists a fair amount of data concerning user-reported experiences with cannabis and the effects that its consumption has on mental state. However, seldom has the question of why been addressed to seek hard evidence that could provide a scientific basis as to why some users tend to respond differently to THC than others. A recent study published in the medical journal Behavioural Brain Research (“Link between Personality and Response to THC Exposure”) sought to address that very question.

Background

Cannabis use, for medicinal or recreational purposes, is a relatively common occurrence worldwide. Approximately 183 million people ranging from 15-64 years old, currently use cannabis. Legislation concerning its legality has seen changes not only within the U.S. but also internationally.

These changes, coupled with changes in professional perception regarding the practical application of cannabis and its derivatives within a medical context, have shed new light on the relevance of this substance throughout multiple forums. As the world-stage directs its spotlight towards cannabis, it does so too for its users. However, due to the recency of the international shift in viewing cannabis as potentially multifaceted, multipurpose, and worthy of scientific exploration, there is currently a lack of substantive information surrounding the topic that researchers are seeking to fill.

Despite the relative dearth of data surrounding cannabis and its effects, plenty of studies have been conducted to document the physical signs and symptoms that users may feel during and post-cannabis consumption. As a result, we currently have a fair bit of insight concerning how cannabis-users, collectively, may feel upon consuming cannabis and its primary psychoactive molecule delta-9-tetrahydrocannabinol (THC). The results have been somewhat of a mixed bag.

Some users report feelings of anxiety, paranoia, and depression, whereas others will report feelings of euphoria, calmness, and relief. Current studies that draw links between cannabis use and the increased risk for the development of anxiety disorders, vulnerability to stress, and depression, neglect to explain any potential reason for these correlations. This study sought to draw insight as to why certain individuals who consume THC may be predisposed to these conditions as opposed to others.

The Study

Researchers hypothesized that the varying effects of cannabis amongst users are due to the difference in personality types of those users. To test their hypothesis, laboratory mice with stress-resilient (“socially dominant”) and stress-vulnerable (“socially submissive”) traits were used to explore the relationship between cannabis and personality type.

Methods

Before undergoing behavioral experiments, mice first needed verification as to whether they possessed either dominant or submissive personality-types. This was done through the aptly named “dominant-submissive relationship” (DSR) test.

In this test, mice were placed into two separate chambers that were connected by a single tunnel. At the center of this tunnel was a food source (milk) that was only accessible to one mouse at a time. The chambers were restricted from access to the tunnel until the beginning of the test.

The mice used in this test had been selectively bred for over 30 generations to have either dominant or submissive characteristics. The purpose of DSR testing was to verify, before experimenting, that these mice were worthy of their preordained dominant or submissive classification.

During DSR testing, dominant and submissive mice of similar weight were paired together and were assessed based on how much time they spent drinking milk. Dominant mice spent a longer time drinking milk than submissive mice. Ultimately, the results of the DSR test were congruent with the personality classifications the mice had been given before testing. After verification, four types of behavioral tests were conducted on the mice, followed by blood testing for a particular type of steroid hormone called “corticosterone.”

Three of the behavioral assessments included a Resistant Stress test, a Tail Suspension Test, and a Forced Swim Test. The fourth was an assessment used to measure addictive-like behaviour called “Conditioned Place Preference (CPP).

CPP testing took place immediately after DSR verification. On the first day of CPP testing, mice were placed into a box containing two compartments of differing colors and patterns separated by dividers. Mice were then observed without dividers to determine which compartment they naturally preferred. For the next four days, mice were administered a placebo-like solution and placed into their compartment of preference (now separated by dividers). During this time, they were also administered THC at either low (1.5mg/kg body weight) or high (15 mg/kg body weight) doses and then were placed into the compartment that they did not naturally prefer. On the final day of the assessment, mice were placed in the center of the two compartments, uninhibited by dividers. Researchers recorded how much time the mice then spent in each compartment.

Following the CPP assessment, there was a 1.5-month “washout” period in which the mice weren’t administered any THC or subject to any further testing before the commencement of the three stress-tests mentioned above. This washout period was implemented so as not to influence the results of the next battery of tests. After the washout period, stress testing commenced following the same structure as CPP testing, albeit with an added stressor applied each day. During this series of stress tests, compartment preference was assessed after THC administration and response to specific stressors that the mice had endured.

Results & Significance

Researchers found that during CPP testing, submissive stress-sensitive mice displayed a strong affinity for their naturally-preferred compartment upon exposure to THC, suggesting that they had an aversion to the drug. It is of note that this result was only observed during the high-dose administration of THC. Dominant stress-resilient mice, however, did not display any compartment preference following either low or high dose THC exposure. This finding suggests that dominant mice did not have as strong of an aversion to THC as submissive mice.

During the second wave of testing in which CPP was assessed before and after the addition of the three stress tests, there was no discernible difference in compartment preference as compared to results collected before the washout period. The results remained similar regardless of THC dose and the employment of stressors indicating acute stress did not affect aversion or affinity to the drug in either dominant or submissive personality types

The Forced Swim test bore particular significance in this study, as this is a test used to evaluate depressive states and the manipulation of those states. Researchers initially hypothesized that short-term THC exposure might lead to lasting behavioral effects, and sought to evaluate the influence of THC on depressive behavior concerning personality.

During the Forced Swim test, mice are placed into a water-filled cylinder from which they cannot escape. “Immobility time” is assessed as a measurement of how long the rodent makes just enough effort to keep its head above water without any further effort to escape. This behavior has been postulated to represent a certain manifestation of despair that, within the parameters of this test, is thought to correlate with depressive-like behavior in humans. In this study, submissive mice displayed a higher immobility time than dominant mice indicating an increase in depression in submissive personalities. However, upon the administration of THC, dominant mice displayed a significant increase in immobility time. This finding suggests that high doses of THC can predispose even socially dominant, stress-resilient individuals to depressive behavior.

After both waves of testing had concluded, researchers measured the concentration of corticosterone in the mice. Corticosterone is a steroid hormone that is elevated in states of anxiety and stress. There is no difference in baseline corticosterone levels between naive submissive and dominant mice. Findings showed that corticosterone levels in both dominant and submissive mice had stayed the same after the administration of low-dose THC. However, upon the administration of high-dose THC, there was a significant elevation of corticosterone seen in both groups.

Limitations & Drawbacks

There is always precaution to be taken when studying animals in an attempt to draw insight into various aspects of human nature. This is further complicated when dealing with arguably less-tangible and nebulous concepts such as behavior and personality.

Although extensive research on animal testing as a model for human insight has garnered a generally affirmative consensus within the scientific community regarding its validity, there is still debate surrounding the practical application of some of these methods and their results.

The Forced Swim test, for example, is carried out twice during experiments in which its application is deemed necessary. Immobility time is measured during the second submersion. If immobility time is noted to increase, then this is interpreted as depressive-like behavior. However, because mice have already become familiar with the test-environment during the first submersion, it could be argued that increased immobility time during the second submersion may arise as a result of learned behavior and a decrease in fear and anxiety, rather than a manifestation of despair.

If we were to argue that the behavioral characteristics of mice are both irrefutably identifiable as well as valid in terms of their further application in the understanding of human behavior, then it would also be prudent to note the limitations of the characteristics studied here. Behavior and personality traits are difficult to confine within a single vacuum, as they tend to exist as the smorgasbord of colors on an artist’s palette, acting upon each other to blend and ultimately form a unique portrait of the individual. We tend to isolate particular behavioral traits to understand them and their utility within this picture better. However, by choosing to observe only a single aspect of this behavioral portrait, such as dominance or submissiveness, we leave ourselves at risk for failing to see the image in its entirety.

Final Thoughts

It is seldom anything less than a daunting endeavor when attempting to provide new, accurate data on a subject such as behavior and personality using an animal model. This endeavor is only further complicated when evaluating the effects of substances such as THC on that behavior. In the pursuit of capturing data that could begin to explain the cause-and-effect relationship between the two, researchers here undoubtedly forayed into a relatively uncharted territory that has yet to be further explored. However, their attempt to do so in this study was very well thought out, thoroughly vetted for validity, and executed. Studies like this ultimately will lay the groundwork for further studies on this subject. And as curious minds continuously broach the subject of personality, behavior and THC, we will start to see the nebulous cloud ensconcing this complex topic slowly dissipate to reveal a detailed and clear portrait of association. This study is an excellent start.

 

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