In a rodent model of chronic social defeat stress, MDMA seems to make the animal stronger.

A new Japanese study found that mice exposed to a chronic social defeat stress condition develop a number of adverse health conditions. MDMA appears to confer resilience in a rodent model of chronic social defeat stress. However, mice that received multiple injections of MDMA (also known as ecstasy, or 3,4-Methylenedioxymethamphetamine) experienced none of these negative health effects. The study appeared in the journal Psychiatry Research.

MDMA is perhaps of the most broadly involved sporting medication on the planet. Empathy and sociability are both enhanced as a result of it. However, it is also known to cause hallucinations and to facilitate a wide range of negative effects on mental health when used for an extended period of time. It was first developed in Germany as part of research into a potential appetite suppressant, but it is now illegal in most of the world.

However, a recent large-scale study of adults in the United States found that ecstasy use was associated with lower rates of mental distress and suicidal ideation. Ecstasy use was linked to a lower risk of serious psychological distress, depression, and suicidal ideation in another study that surveyed over 200,000 adults in the United States from 2015 to 2020. In contrast, the use of the hallucinogenic drug LSD (lysergic acid diethylamide) was linked in the same study to an increased risk of depression and suicidal ideation.

The potential use of MDMA as a treatment for post-traumatic stress disorder (PTSD) has also been highlighted by recent studies. Ecstasy, in comparison to a placebo, was found to significantly lessen the severity of symptoms in patients with severe posttraumatic stress disorder, according to a study. Lead researcher Youge Qu and her colleagues wanted to see if giving mice MDMA on a regular basis would make them more resilient to the effects of chronic social defeat stress in their new study.

A scientific procedure known as chronic social defeat stress (CSDS) involves placing a mouse in an enclosed space with a larger, more aggressive mouse. The mouse receiving this treatment is defeated and forced into a submissive position (social defeat) during a confrontation with the other mouse.

This procedure is typically repeated every day for ten days. In mice exposed to the chronic social defeat stress protocol, it is known to cause effects similar to depression as well as a number of easily detectable effects like a decrease in sucrose preference and an increase in spleen weight. Because of this, research on mice makes extensive use of it.

This study was conducted on 7-week-old mice, while larger 13-week-old mice served as aggressors. The mice always had access to water and food. There were three groups of them. The first group served as a baseline. Instead of MDMA, it received a saline solution, and it was not subjected to persistent social defeat stress. The second group was given a saline solution each day for 10 days and subjected to chronic social defeat stress with a different larger aggressor mouse. MDMA was administered to the third group as part of the chronic social defeat protocol.

Using a sucrose preference test, the researchers checked to see if mice had lost the ability to feel pleasure (anhedonia), which was one of the expected side effects of the chronic social defeat stress treatment. They also took blood from their hearts at the end of the treatment, measured the levels of several compounds that are known to be indicators of negative effects of the chronic social defeat stress protocol, and took samples of their stools to look at the microorganisms in their guts.

One of the known negative effects of the chronic social defeat protocol is that mice exposed to it who received saline injections instead of MDMA had larger spleens. Anhedonia was also evidenced by these mice’s decreased preference for sucrose. In mice given a saline injection, all of the other indicators of negative effects of the chronic social defeat stress protocols were elevated. Mice that received MDMA injections exhibited none of these negative changes.

In addition, when mice were subjected to the chronic social defeat stress protocol and given saline injections, the researchers observed changes in the composition of the gut microbes. Mice that underwent the same procedure but received MDMA injections showed no signs of these changes. These modifications were attributed by the researchers to the so-called gut-microbiota-brain axis, a set of chemical pathways that allow brain activity and gut microorganisms to interact.

“Through the gut–microbiota–brain axis, the present study suggests that repeated MDMA use may be associated with resilience in mice subjected to CSDS.” Abnormalities in the gut-microbiota-brain axis, including metabolites derived from microbes, may increase vulnerability to stress-related disorders. In conclusion, the researchers stated, “MDMA would be a prophylactic and therapeutic drug to prevent the onset of stress-related disorders.”

The study provides insight into stress’s biochemical mechanisms. But it also has restrictions that need to be taken into consideration. Notably, the study did not provide evidence that the gut-microbiota-brain axis helped mice given MDMA become more resilient to stress. In addition, it is still unknown if the human effects of MDMA can be replicated in the same way that they were in mice, and even if they could, would they be desirable.

Instead of resilience, the observed effect could be drug-induced indifference to social situations. Even if it does save the user from the stress that these situations might cause, indifference to and neglect of social situations (such as jobs, family responsibilities, financial obligations, and other social responsibilities) is generally regarded as an undesirable effect of drug use.

The study, titled “Repeated use of 3,4-methylenedioxymethamphetamine is associated with the resilience in mice after chronic social defeat stress,” was published in Youge Qu, Akifumi Eguchi, Xiayun Wan, Li Ma, Lijia Chang, Jiajing Shan, Yong Yang, Chisato Mori, and Kenji Hashimoto wrote “A role of gut–microbiota–brain axis.”

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