Increasing consideration is being given to 3,4-Methylene-dioxymethamphetamine (MDMA or “ecstasy”) as a possible treatment approach for depression.

In a review of current literature published in Therapeutic Advances in Psychopharmacology, authors Rachel Patel of Green Templeton College and Daniel Titheradge of St Hugh’s College discuss the pros and cons of treating depression with MDMA, noting that clinical trials already in place examining the utility of treating PTSD with MDMA have contributed to an interest in examining how MDMA may be used to treat depression.

How might MDMA be helpful in treating depression? Essentially, the neurochemical mechanisms of MDMA link to the monoamine theory of depression, whereby the reduced activity of neurotransmitters (primarily serotonin, or 5-HT) is increased by MDMA. In addition, the capacity of the drug to make serotonin quickly available at receptor sites has appeal over traditional selective serotonin-reuptake inhibitors (SSRI), anti-depressant medications that can take several weeks to take effect.

“MDMA has the potential to act as a rapid-onset antidepressant via its modulation of the 5-HT system and as an augmentation strategy in cognitive therapy,” the researchers said.

As an outlawed drug in the United States and the United Kingdom, there is hesitancy in tapping into MDMA’s potential. While the drug is classified primarily as a stimulant, its mild hallucinogenic properties also contribute to hesitancy and the stigma attached to hallucinogenic drugs.

Additionally, neurotoxicity of MDMA is a concern. For instance, Patel and Titheradge note previous research reporting reduced levels of serotonin and its metabolites in the brain tissue and cerebral spinal fluid in a sample of those who died due to MDMA toxicity. Another in vivo study showed a reduction in serotonin transporter (SERT or 5-HTT; the protein that transports serotonin) density, an indication of neurotoxicity.

Discrepancies in several additional studies are noted, however, and more conclusive research is needed to determine how MDMA may be neurotoxic before moving forward, with the authors contending that “despite MDMA passing safety measures for its use in clinical trials of PTSD, we believe that until the discrepancies in neurotoxicity data are resolved, it is unlikely that MDMA will be explored as a rapid-onset antidepressant because of the emphasis in both depression pathophysiology and MDMA neurotoxicity on 5-HT.”

“The data from PTSD trials of MDMA assisted psychotherapy set a promising precedent that can likely be applied to depression. The use of MDMA as a standalone rapid-onset antidepressant is theoretically well-grounded, but lacks proof of concept,” Patel and Titheradge wrote.

Research on the psychological effects of MDMA have been conducted on animals, in humans using self-report and prospective data, and in clinical trials with human subjects. In general, findings indicate promise in expanding upon current research, especially in using MDMA treatment as a supplement to psychotherapy to possibly enhance therapeutic effectiveness in the treatment of depression. Current clinical trials using MDMA in the treatment of PTSD may springboard this research forward. Stay tuned…