La psychothérapie assistée par la MDMA dans la prise en charge du syndrome de stress post-traumatique

Posttraumatic stress disorder (PTSD) is estimated to remain chronic and severe for 25–50% of patients despite psychotherapeutic treatment. Part of the reasons is that patients with PTSD can have difficulties in establishing a good therapeutical alliance with the therapist. Moreover, they often fail to re-think the content of the trauma without being overwhelmed by negative emotions and tend to rely on avoidance strategies and/or to abandon the therapy. MDMA (“ecstasy”) is a drug classified as an entactogen (en “within”, tactus “touch”, and gen “produce”), an amphetamine with psychedelic properties that possesses psychopharmacological properties to overcome these issues. Indeed, MDMA triggers the release of oxytocin, which favors the establishment of interpersonal relationship based on kindness and trust. Moreover, MDMA diminishes the activity of the amygdale, allowing patients to work on challenging memories with less fear and anxiety. Finally, MDMA may also provide access to meaningful spiritual experiences, release of tensions and a sense of healing on a non-verbal level that are not completely understood. But are viewed as important by patients. Today, there is no evidence that the use of MDMA in a clinical setting has bad neurologic, psychological or cognitive consequences. Results of phase II trials in the United States and Europe confirm that MDMA favors psychotherapy's outcome without severe adverse effects. Phase III trials are underway. The Multidisciplinary Association for Psychedelic Studies (MAPS) has published online a method proposal and trains therapists in MDMA-assisted psychotherapy.ConclusionFood and Drug Administration (FDA) and European Medicines Agency (EMA) could approve this therapeutic tool in the coming years.     

The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task

The current study used the partially-baited radial-arm maze paradigm to study the effects of a single-treatment high-dose exposure ('binge') to MDMA (± 3,4-methylenedioxymethaphemtamine or 'Ecstasy') on memory task acquisition. Sprague-Dawley rats were administered a binge dose (4 × 10 mg/kg) of MDMA and their ability to subsequently acquire the radial-arm maze task was compared against saline controls. The MDMA-treated rats were significantly slower to learn the task and made more reference memory errors than the controls. Working memory function was found to be relatively unimpaired. Following a reversal of task rules the MDMA-treated rats were again significantly slower to acquire the appropriate rule despite having eventually achieved a similar level of overall performance as control rats. However evidence of drug tolerance was found when all rats were challenged with an acute low dose of MDMA (1 × 4.0 mg/kg) because the binge MDMA rats were relatively less impaired. Therefore, although binge treated MDMA rats were able to achieve very accurate performance equivalent to the controls they took significantly longer to do this and were less able to adapt their behavior to a change in task rules. In addition the binge treated MDMA rats displayed tolerance to acute MDMA exposure. These findings are consistent with the possibility that human Ecstasy users may show deficits in acquiring information and may experience deficits in cognitive flexibility as well as developing tolerance to the drug with repeated exposure.     

Construct Validity of the Balloon Analogue Risk Task (BART): Relationship with MDMA Use by Inner-City Drug Users in Residential Treatment

In a program of research assessing the validity of the balloon analogue risk task (BART; C. W. Lejuez et al., 2002) as a measure of risk taking, the BART was administered to a sample of inner-city drug users in residential treatment (n = 76). Construct validity of the BART was evaluated by measuring risk-taking behavior and 3,4-methylenedioxymethamphetamine (MDMA) use while controlling for self-reported impulsivity, sensation seeking, polysubstance use, and demographic variables. Supporting the construct validity of the BART, while controlling for interrelated variables in the context of logistic regression analyses, (BART) risk-taking propensity accounted for significant incremental variance in differentiating MDMA users from non-users. BART scores, polysubstance use, and younger age were most associated with MDMA use, and together these variables were associated with 91% classification accuracy in predicting MDMA use.     

Mapping Open-Field Behavior in Rats: Applicability Across Sexes

Open-field behavior of female and male Sprague-Dawley rats was plotted on a map using scores derived from a principal-component analysis. As reference points on the map, three treatment conditions were used: electric shock, extensive stroking, and additional trials after habituation to the field. Five measures were used: ambulation, penetration into the inner square, rearing, defecation, and urination. The behaviors in each treatment condition clearly cohered with each other on the map, regardless of sex difference in raw scores. This coherence shows that the nature of the emotional behavior caused by the present treatments is similar across sexes, indicating, to some degree, the applicability of the map across the sexes. The additional experiment (concerning the estrus effect on the open-field behavior) suggests that the estrus effect is not large enough to compromise the validity of the map, which was constructed on the basis of the data without control of the estrus effect.     

Effects of acute,subchronic and intermittent MDMA (‘ECSTASY’) administration on agonistic interactions between male mice

Recent studies suggest that acute administration of 3,4‐methylenedioxymethamphetamine (MDMA), an amphetamine derivative popularly known as “ecstasy,” produces an antiaggressive effect in male mice. However, there is no evidence with respect to the development of tolerance or sensitization after its subchronic or intermittent administration. In this study, we examined the action of low to moderate doses of MDMA (1.25, 2.5 and 5 mg/kg, i.p), administered acutely, subchronically (for 7 days) or intermittently, on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic “standard opponents” 30 minutes after the drug administration, and the encounters were videotaped and evaluated using an ethologically based analysis. Acute treatment with MDMA provoked a significant reduction of aggressive behaviors, without altering immobility. However, this action was only selective at 1.25 mg/kg. With the intermediate (2.5 mg/kg) and the highest doses (5 mg/kg) of the drug, it was observed a significant decrease of offensive behaviors, accompanied by an increase of exploration from a distance, avoidance/flee and defense/submission behaviors. This ethopharmacological profile could indicate the existence of an anxiogenic‐like effect of MDMA. The overall picture of the effects of MDMA was very similar in the acutely, intermittently and daily treated animals. No tolerance or sensitization to the actions of the drug was developed after its repeated or intermittent administration.