How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale

Exposure therapy is effective for anxiety disorders but is underused, with patients often prescribed SSRIs or benzodiazepines that may hinder extinction learning. Given trials testing MDMA with psychotherapy for treatment-resistant anxiety, three mechanisms are proposed: MDMA increases oxytocin, strengthening the therapeutic alliance; it increases ventromedial prefrontal activity and decreases amygdala activity, improving emotional regulation and reducing avoidance; and it increases norepinephrine and cortisol, facilitating emotional engagement and extinction of learned fear. These effects may allow patients to feel safe while processing emotions, as seen in case reports. Further studies are needed.

Study at a glance

Abstract

Abstract Exposure therapy is known to be an effective treatment for anxiety disorders. Nevertheless, exposure is not used as much as it should be, and instead patients are often given supportive medications such as serotonin reuptake inhibitors (SSRIs) and benzodiazepines, which may even interfere with the extinction learning that is the aim of treatment. Given that randomized controlled trials are now investigating a few doses of ±3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) in combination with psychotherapy for treatment-resistant anxiety disorders, we would like to suggest the following three mechanisms for this potentially important new approach: 1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations. Thus, MDMA has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as described in case reports of MDMA-augmented psychotherapy. Further clinical and preclinical studies of the therapeutic value of MDMA are indicated.