MDMA-assisted psychotherapy

PTSD inhibits a subject's ability to respond appropriately to trauma-related stimuli.[7] The current model of PTSD proposes that it results from amplified and uncontrolled responses from the amygdala to trauma-specific cues.[10] Oxytocin, which is increased by MDMA, has been found to increase trust and emotional awareness and reduce amygdala responses as well as reduce coupling of the amygdala to brainstem regions associated with autonomic and behavioral characteristics of fear.[16][17][18] It has been proposed that these effects foster memory reconsolidation by allowing the patient to access the traumatic memory while feeling detached from the sense of imminent threat.[10]

In 2017, the treatment was granted breakthrough therapy designation by the FDA, a designation that indicates that there is preliminary evidence that an intervention might offer a substantial improvement over other options for a serious health condition.[5]

MDMA was first synthesized by German pharmaceutical company Merck KGaA in the early 1900s as an intermediate in the synthesis of another compound. Its psychoactive effects were not noted until the early 1960s. In the 1960s and 1970s, the drug was used in psychotherapy, although it was not an approved drug and no clinical trials had been performed. The drug was studied in Switzerland for use in individual, couple, and group therapies until 1993, when the Swiss Ministry of Health withdrew permission to use MDMA and LSD by psychiatrists due to concerns about lack of research methodology.[20]

In 1986, MDMA was classed as a Schedule 1 drug by the United Nations according to its Convention on Psychotropic Substances of 1971 due to its high potential for abuse, and most research was stopped.[7] Researchers interested in MDMA for use in psychotherapy founded and funded the Multidisciplinary Association for Psychedelic Studies (MAPS) in response. The US Food and Drug Administration (FDA) and Drug Enforcement Administration (DEA) granted approval for researching MDMA's efficacy as an adjunct to psychotherapy in 2004, and the first trial was carried out in 2011.[21]

MDMA's effects vary across people and settings and include adverse outcomes.[6][9] The drug causes neurotransmitter activation across the main neural pathways (including serotonin and dopamine, noradrenaline) that can result in large mood swings. The memories that emerge under the influence of MDMA can evoke unwanted emotions.[6] Side effects of MDMA use by recreational users include appetite fluctuations, food cravings, and disordered eating.[6]

Once the effects of MDMA wear off, there is a "period of neurochemical depletion" that invokes anhedonia, lethargy, anger, depression, irritability, brooding, greater everyday stress, altered pain thresholds, changes in sleep, and bad dreams, especially in female participants.[6] The symptoms are thought to be due to depletion of serotonin, as a result of the large release of serotonin triggered by MDMA, and have been called "neurotoxic in terms of causing serotonergic dysfunction".[6]

There are also concerns surrounding "drug-dependent learning" — the theory that patients will return to the drug to access the state they were in when on the drug in therapy.[6]

There were 92 MDMA related deaths in England and Wales in 2018, up from 56 the year before,[22] and 10,000 hospitalizations for MDMA related illness/injury in 2011 in the US.[8] However no such cases have (as of 2021) been reported for clinical settings.

Media reports and statements of academic authors have often transmitted the view of MDMA as a possible medicine or treatment rather than as an adjunct to psychotherapy.[7] This has been considered as dangerous, because it could lead people to believe that MDMA is an effective treatment alone, without concomitant psychotherapy.[7]