Summary: New research shows that rats with naturally higher basal levels of the stress hormone are significantly more likely to self-administer cannabis vapor. For several weeks, the rats were allowed to pick their noses for cannabis, and those with elevated corticosterone levels showed the strongest drug-seeking behavior.
The study also found links between cannabis use, low endocannabinoid levels, and reduced cognitive flexibility, suggesting multiple interacting biological factors. The findings point to possible early markers of vulnerability to cannabis dependence and help explain why stress plays such a central role in habitual use.
Key facts
Stress predicts use: Rats with naturally higher basal stress hormones self-administered significantly more cannabis vapor. Cognitive flexibility: Animals less able to adapt to changing rules showed stronger cannabis-seeking behavior. Endocannabinoid link: Lower levels of endocannabinoids combined with high morning stress hormones also predicted higher drug use.
Source: Washington State University
It’s not just people: When given the chance, rats can also use cannabis to cope with stress, according to a study by researchers at Washington State University.
Published in the journal Neuropsychopharmacology, the study was designed to examine cannabis-seeking behavior and found that rats with higher natural stress levels are much more likely to self-administer the popular recreational drug.
“We put rats through this extensive battery of biological and behavioral tests, and what we found was that when we look at all of these different factors and all of the variables that we measured, stress levels seem to be the most important when it comes to cannabis use,” said Ryan McLaughlin, an associate professor in the WSU College of Veterinary Medicine.
Looking at traits ranging from social behaviors to sex, cognition, reward and arousal, McLaughlin and his team of undergraduate and graduate researchers created a behavioral profile for each rat.
Then, over the course of three weeks, rats were observed for one hour daily while they were given the option to self-administer cannabis by sticking their nose into a vapor port to release a three-second dispersion of cannabis vapor into an airtight chamber.
During that one-hour period, the student researchers tracked the number of “nose pokes” for each rat and found a direct correlation with the number of nose pokes and baseline levels of the stress hormone.
By measuring the stress hormone corticosterone in rodents, the equivalent of the stress hormone cortisol in humans, the team found that rats with higher natural levels of the stress hormone were much more likely to self-administer cannabis.
“If you really want to boil it down, there are baseline levels of stress hormones that can predict rates of cannabis self-administration, and I think that only makes sense given that the most common reason people regularly use cannabis is to deal with stress,” McLaughlin said.
He said it’s important to note that it was a rat’s resting basal stress levels that were associated with cannabis self-administration, not stress that fluctuates in real time with exercise or mentally challenging tasks. Stress hormone levels were also calculated after exposure to a stressor and showed no significant link with cannabis-seeking behavior.
There were also significant relationships between rates of cannabis self-administration and measures of “cognitive flexibility,” which is our ability to adapt to changing rules.
“Animals that were less flexible in switching between rules, when we tested them in a cognitive task, tended to show higher rates of cannabis-seeking behavior,” he said. “So the animals that rely more on visual cues to guide their decision making, those rats, when we tested their motivation to self-administer cannabis vapor, were also very motivated rats.”
The study also identified a link between high morning corticosterone and low endocannabinoid levels with cannabis self-administration, although not as strong as initial stress.
Endocannabinoids are compounds that are produced on demand to help the body maintain a state of physiological balance or homeostasis.
“There is some thought as to why people might be more likely to use cannabis, and that perhaps THC serves as a reasonable substitute for endocannabinoids in people who have lower endocannabinoid levels,” McLaughlin said. “So maybe there’s more of a push to supplement that with cannabis.”
As more states decriminalize cannabis and legalize recreational cannabis, McLaughlin said it’s critical to understand the effects of the drug and the consequences of drug abuse.
“Our findings highlight potential early or pre-use markers that could one day support screening and prevention strategies,” McLaughlin said. “I could certainly imagine a scenario where having an baseline cortisol assessment could provide some level of information about whether there is a greater propensity to develop problematic patterns of drug use later in life.”
Key questions answered:
A: Rats with naturally higher basal levels of the stress hormone were much more likely to self-administer cannabis vapor. This suggests that underlying chronic stress, not moment-to-moment stress, may be an important driver of cannabis-seeking behavior.
A: Rats with lower cognitive flexibility and greater reliance on visual cues showed higher rates of cannabis self-administration. These traits may reflect difficulty adapting to changing rules, which predicted greater motivation to seek drugs.
A: Rats with high morning stress hormones and low levels of endocannabinoids also showed greater cannabis consumption. This supports the idea that some people may turn to cannabis to compensate for low natural endocannabinoid signaling, especially when stress is chronically high.
Editorial notes:
This article was edited by a Neuroscience News editor. Magazine article reviewed in its entirety. Additional context added by our staff.
About this research news on stress and cannabis use disorder
Author: Josh Babcock
Source: Washington State University
Contact: Josh Babcock – Washington State University
Image: Image is credited to Neuroscience News.
Original Research: Closed access.
“Identification of biological and behavioral predictors of cannabis vapor self-administration in rats” by Ryan McLaughlin et al. Neuropsychopharmacology
Abstract
Identification of biological and behavioral predictors of cannabis vapor self-administration in rats
The recent wave of recreational cannabis legalization in the United States has highlighted the importance of identifying predictors of individual variability in cannabis use. While a subset of recreational cannabis users will meet the diagnostic criteria for cannabis use disorder, many do not, making it critical to characterize the traits that confer both vulnerability and resilience.
However, progress in identifying relevant predictors has been hampered by limited mechanistic insight and a lack of translationally relevant animal models of cannabis use.
To address this, we employed a rat model of cannabis vapor self-administration that utilizes whole cannabis plant extract and mimics the intrapulmonary ingestion route typically used in humans.
Using this model, we sought to identify biological and behavioral predictors of motivation to self-administer vaporized cannabis.
Male and female Long-Evans rats (N = 48) underwent a battery of trials indexing behavioral domains aligned with the NIMH Research Domain Criteria (RDoC) prior to self-administration training. After four weeks of cannabis vapor self-administration (1-h sessions daily), motivation for cannabis vapor was assessed using a 3-h fixed-ratio escalation (FRE) procedure.
A series of linear regressions revealed that the domains of Social Processes, Arousal/Regulation Systems, Cognition, and Positive Valence significantly predicted the number of cannabis vapor deliveries obtained during the FRE test. Specifically, higher baseline corticosterone (CORT), lower morning anandamide, poorer set-shift performance, superior discrimination of visual cues, and greater social preparedness during adolescence predicted response to cannabis.
The Negative Valence domain was not a significant predictor. A multivariate machine learning approach combining principal components analysis and permutation significance further identified baseline CORT and set-shift performance as the strongest predictors of response to vaporized cannabis.
These findings highlight individual differences in stress regulation and cognitive flexibility as potential risk factors for cannabis use propensity and demonstrate the utility of leveraging the RDoC framework to identify relevant phenotypes in rodents that may extend to human psychiatric conditions.
