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Cannabis Reduces Stress in Female Rats, Study Finds

By Alexander Beadle

Published: Jan 05, 2021   
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Female rats, trained to inhale cannabis vapor daily for one month, developed a blunted psychological response to stress, according to new research out of Washington State University.

The study, published in the journal Neurobiology of Stress, represents a significant step forward for researchers in establishing whether cannabis use leads to differences in the stress response, or vice versa.

Notably, the study saw no psychological changes in the responses of male rats, indicating there may also be significant differences in how chronic cannabis use affects men and women.

Can cannabis use curb feelings of stress?

Stress relief is one of the most commonly cited motivations for using cannabis, and one that is backed up by numerous observational studies linking acute cannabis use to reductions in perceived feelings of stress.

But scientifically, researchers have so far struggled to determine whether a muted stress response occurs as a consequence of cannabis use, or whether a pre-existing difference in stress response might actually raise the likelihood of cannabis use. This is because ethically and practically, researchers often cannot ask randomly assigned study participants to use or abstain from cannabis before the beginning of an experiment.

But by using an animal model that behaves similarly to humans, such as the rats, researchers can begin to answer these big questions.

“We were able to show pretty conclusively that chronic cannabis use can, in fact, significantly dampen stress reactivity in female rats,” said Carrie Cuttler, an assistant professor of psychology at WSU and co-author of the study, in a statement. “Until now, no one has been able to establish whether this blunted stress response is the cause or the consequence of cannabis use.”

Cannabis potency, sex, and the stress response

Animal studies do present challenges of their own, especially when examining stress. For example, it is quite common for mouse model studies on cannabis use to inject the study rats with isolated cannabinoids. Even the stress itself can be detrimental.

“The problem with this approach is that it’s stressful to the rats and doesn’t recruit the same neurobiological circuits that taking a drug of your own volition does,” said Ryan McLaughlin, an assistant professor of integrative physiology and neuroscience at WSU and a co-author on the new paper.“ To address this challenge, we developed a more natural cannabis delivery system that enables rats to self-administer vaporized cannabis whenever they feel like it.”

The team at WSU trained the rats to poke their noses into a hole when they wanted to receive a dose. Their noses would break an infrared beam shone across the opening of the hole, prompting a puff of vaporized cannabis extract to be released around their nose. The rats were split into four groups: one control group, and three that were given access to either a low, medium, or high potency cannabis extract. Stress was measured by comparing measured levels of the stress hormone corticosterone before and after the 30-day study period.

At the beginning of the experiment, all the rats had similar spikes in corticosterone when exposed to a stressful situation. But after 30 days, the subgroup of female rats that had been given access to the medium potency extract had a significantly more muted stress response than the other groups.

Notably, the medium potency group actually had the highest blood levels of THC at the end of the experiment, possibly because they visited the dosing station more frequently as the study progressed – a trend not seen in the mice given the highest of the three active doses.

“Interestingly, we found that the rats that were given access to higher potency cannabis tended to respond less and had lower concentrations of THC in their blood after the experiment than the rats that had access to the medium potency cannabis,” McLaughlin said. “What is causing this difference as well as why females seem to be more receptive to the stress muting effects of cannabis are both things we plan to investigate in the future.”

Cannabis and the human stress response

The dulling of the stress response in the medium dose group of female rats suggests that cannabis use may also be able to confer some resilience to stress in humans, too.

However, the WSU researchers go on to highlight that the release of stress hormones does serve a useful purpose in the human body, allowing it to mobilize energy stores and better respond to potential threats. As such, more research on this altered stress response may have to be done before more conclusions are drawn.

“An inability to mount a proper hormonal response to stress could have detrimental effects that could potentially be harmful to the individual,” Cuttler said. “Research on cannabis is really just now ramping up because of legalization, and our work going forward will play an important role in better understanding both the benefits and potential consequences of chronic cannabis use in women and men.”


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