The party drug ecstasy can only take effect if the serotonin system is functioning properly. This surprising finding was made by a team from Marburg working within the Collaborative Research Center “Treatment Expectation”. The findings of the research team led by Prof. Markus Wöhr shed new light on fundamental mechanisms of the reward system and could have significant implications for psychotherapy.
MDMA needs serotonin: Researcher Tianhua Wang with a laboratory rat
MDMA, the active ingredient in the party drug ecstasy (XTC), typically induces euphoria, boosts energy levels and heightens sensory perceptions. However, these effects can only occur if there is sufficient serotonin in the brain. If this neurotransmitter, also known as the “happiness hormone”, is lacking, the drug has virtually no effect. This was shown by a study conducted by a research team led by Prof. Markus Wöhr, a biopsychologist and behavioral neuroscientist at the University of Marburg, who also heads projekt A09 within the CRC/TRR 289.
The team conducted its experiments on laboratory rats, which typically react to MDMA in a manner similar to humans. However, due to a genetic mutation, some of the rats were unable to produce serotonin, or produced very little. These animals did not exhibit the usual effects after being administered MDMA.
What was particularly surprising to the researchers was that the rats lacking serotonin in their brains did not even become particularly active after being given MDMA. Yet the drug increases the availability of dopamine in the body, a neurotransmitter typically associated with the urge to move and motivation. “Some rats even seemed to have fallen asleep and that in response to a psychostimulant!” says Prof. Wöhr, describing his team’s observations. “The effects depend almost entirely on serotonin”, explains study leader Tianhua Wang. “Without serotonin, there is no increase in motor activity”. The researchers have published their surprising findings in the journal British Journal of Pharmacology.
A serotonin deficiency could interfere with the effectiveness of new clinical applications
These new findings are bringing the neurotransmitter serotonin more into the spotlight of MDMA research – both in basic science and in clinical applications. MDMA is currently being studied in trials for use in psychotherapy, such as for post-traumatic stress disorder. However, the new study suggests that the effectiveness of such approaches may depend crucially on how well a patient’s serotonin system functions.
New perspectives are also emerging for addiction research: While it was previously assumed that dopamine was primarily responsible for the urge to move triggered by MDMA, the research team’s data show that serotonin is indispensable for this – and thus plays a central role in the drug’s typical activating and mood-enhancing effects.
New insights thanks to laughing rats
For the study, the researchers examined the behavior of rats that, due to a genetic defect, are completely or partially lacking the neurotransmitter serotonin. The animals were given MDMA and were then observed in specialized testing environments: The study measured both physical activity and the occurrence of so-called 50-kilohertz ultrasonic vocalisations, which are interpreted as “rat laughter” and are considered an indicator of a positive mood. The clear result: While normal animals became highly active after receiving MDMA and emitted numerous sounds of joy, rats without serotonin in their brains showed neither activation nor signs of such a euphoria-like reaction.
These findings help provide a more precise understanding of the mechanisms of action of MDMA – an important foundation for better assessing both the therapeutic applications and the risks of the drug in the future. Since dopamine and serotonin also play a role in the development of placebo and nocebo effects, the results also raise new questions for research into the impact of treatment expectations.