MDMA Could Help Erase Conditioned Fear

January 4, 2016 | by Ben Taub

photo credit: 3,4-methylenedioxy-methamphetamine, or MDMA, may play a role in treating post-traumatic stress disorder. Zerbor/Shutterstock

Despite being listed as a Schedule 1 substance by the U.S. Drug Enforcement Administration, MDMA has for a number of decades attracted the attention of medical experts who believe it may facilitate a range of psychotherapies. A recent study appears to lend credence to this assertion by highlighting the ability of MDMA to extinguish conditioned fear in mice, leading researchers to hypothesize that the substance could help to treat post-traumatic stress disorder (PTSD).

PTSD is caused by exposure to disturbing events, resulting in the development of persistent and recurring distress. It is common among war veterans who may have witnessed shocking scenes on the battlefield, as well as those who have lived through a range of other upsetting episodes. Previous small-scale clinical studies have indicated that MDMA may have a long-lasting positive effect on PTSD symptoms, alleviating anxiety and fear, although the mechanism by which the molecule produces these improvements has until now remained poorly understood.

In a recent study that appeared in the journal Translational Psychiatry, a team of scientists from Emory University sought to test the hypothesis that MDMA may somehow contribute to the extinction of learned fear. To do so, they induced a cued fear conditioning response in mice, by repeatedly pairing an audible tone with a mild electric shock to the foot. Eventually, the mice learned to associate the two, and would freeze in fear whenever they heard the sound.

The team then administered some of the mice with MDMA in order to test the effect this would have on the extinction of this conditioned fear when the tone was played in the absence of the electric shock. They found that the drug “persistently and robustly enhanced long-term extinction [of fear] when administered before extinction training,” as those mice who had received MDMA stopped freezing when they heard the sound much quicker than those who had not.

PTSD often affects soldiers and veterans who have experienced disturbing events while in combat. John Gomez/Shutterstock

The researchers then sought to determine the pathway behind this effect by measuring neuronal activity in the amygdala and medial prefrontal cortex – areas of the brain that have previously been shown to play a role in the extinction of learned responses. They discovered an increased expression of a gene called BDNF in the amygdala. This gene provides instructions for the creation of a protein called brain-derived neurotrophic factor, which promotes the development and survival of neuronal cells, and is therefore of great importance to cognitive function.

As a final step, the researchers repeated the experiment using mice that had been administered with a particular antibody that disrupts BDNF signalling. Their results showed that the effect of MDMA on fear extinction was completely abolished in these mice, supporting the conclusion that the drug helps to erase learned fear by promoting the expression of BDNF.

Though more research is needed to determine how MDMA may be used to treat PTSD in humans, the researchers believe their findings could provide an important stepping-stone in the development of novel therapies. In a statement, study coauthor Matthew Young explained that “this is a useful model for understanding the learning and memory processes required for long-term recovery from PTSD because it resembles exposure-based therapy, wherein repeated exposure to a fear-eliciting stimulus or memory promotes a reduced fear response to future reminders of the trauma.”