by A new experiment in Japan has shown that when mice are subjected to a chronic state of stress from social defeat, they develop a number of adverse health conditions. However, these harmful conditions were absent in mice repeatedly injected with MDMA (3,4-methylenedioxymethamphetamine), also known as the club drug ecstasy. The study was published in Psychiatric Research.
MDMA is one of the most commonly used recreational drugs in the world. It creates prosocial feelings and encourages empathy and sociability. However, it is also known to produce hallucinogenic effects and promote a variety of negative mental health outcomes with prolonged use. Originally developed in Germany as part of research into a possible appetite suppressant, it is now banned in most parts of the world.
On the other hand, a recent large study of adults in the US found that ecstasy use was associated with a lower likelihood of mental distress and suicidal thoughts. Another study, which ran between 2015 and 2020 and involved over 200,000 US adults, linked ecstasy use to a reduced likelihood of serious mental distress, depression and suicidal thoughts. This was in contrast to taking the hallucinogenic drug LSD (lysergic acid diethylamide), which was linked to an increased likelihood of depression and suicidal thoughts in the same study.
Recent studies have also brought into focus the potential use of MDMA to treat post-traumatic stress disorder (PTSD). One study reported that ecstasy could produce a significant reduction in the intensity of symptoms in patients with severe post-traumatic stress disorder compared to placebo. In their new study, lead researcher Youge Qu and her colleagues wanted to investigate whether repeatedly dosing mice with MDMA would help them become more resilient to the effects of chronic stress from social defeats.
Chronic social defeat stress (CSDS) is a protocol (scientific procedure) in which a mouse is exposed to a larger aggressive mouse in an enclosed space. A confrontation between the two mice ensues, in which the treated mouse is defeated and pushed into a subordinate position (social defeat).
Typically, this procedure is repeated daily for 10 days. The chronic social stress protocol is known to produce effects similar to depression in mice exposed to it, along with a number of easily detectable effects such as: B. an increased weight of the spleen and a lower preference for sucrose. For this reason, it is used extensively in research on mice.
This study was performed on 7-week-old mice, while 13-week-old (i.e., larger) mice were used as attackers. Mice had water and food available at all times. They were divided into three groups. The first group was a control. It received saline (instead of MDMA) and was not subjected to chronic defeat social stress. The second group was subjected to chronic stress from social defeat for 10 days, using a different larger aggressor mouse each day and given a saline solution. The third group underwent the Chronic Social Defeat Protocol and received MDMA.
At certain points, the researchers tested whether mice had lost the ability to feel pleasure (anhedonia) using a sucrose preference test (one of the expected effects of treating chronic stress from social defeat). They also took blood from their hearts, stool samples at the end of treatment to analyze the composition of microorganisms in their gut, and measured the levels of several compounds known to be indicators of adverse effects of the chronic social stress protocol defeats are.
Mice exposed to the chronic social defeat protocol but injected with saline instead of MDMA had increased spleen weight, which is one of the known adverse consequences of this protocol. These mice also had a decreased preference for sucrose, indicating anhedonia. In mice injected with saline, all other indicators of adverse effects of chronic stress protocols for social defeat were increased. All of these adverse changes were absent in mice that received MDMA injections.
In addition, the researchers found changes in the composition of gut microbes in mice exposed to the chronic social defeat stress protocol and injected with saline. These changes were absent in mice subjected to the same protocol but injected with MDMA. The researchers attributed these changes to the so-called gut-microbiota-brain axis, a mechanism of chemical signaling pathways that allow brain activity to interact with microorganisms in the gut.
“The present study suggests that repeated MDMA exposure may be associated with resilience in mice exposed to CSDS via the gut-microbiota-brain axis. It is likely that abnormalities in the gut-microbiota-brain axis, including microbial-derived metabolites, may contribute to susceptibility to stress-related disorders. Finally, MDMA would be a prophylactic and therapeutic drug to prevent the onset of stress-related disorders,” the researchers concluded.
The study sheds light on the biochemical mechanisms of stress. However, there are also limitations that must be considered. Notably, the study provided no evidence for the role of the gut-microbiota-brain axis in the development of stress resistance in mice given MDMA. In addition, it remains unknown whether the mechanism by which the effects of MDMA were achieved in mice can be reproduced in humans and, if possible, whether this would be desirable.
The observed effect could also be drug-related indifference to social situations instead of resilience. Indifference to and neglect of social situations (such as work, family responsibilities, financial responsibilities, and other social responsibilities) in people who use drugs is generally considered to be an undesirable effect of drug use, even if it protects the person from the effects of stress that causes them could cause situations.
The publication, “Repeated use of 3,4-methylenedioxymethamphetamine is associated with resilience in mice after chronic stress from social defeat: A role of the gut-microbiota-brain axis” was published by Youge Qu, Akifumi Eguchi, Xiayun Wan, and Li Ma authored , Lijia Chang, Jiajing Shan, Yong Yang, Chisato Mori and Kenji Hashimoto.
