Dose-Response Study of MDMA-assisted Psychotherapy in People With PTSD

Posttraumatic Stress Disorder Clinical Trial

Official title: A Randomized, Double-Blind, Dose Response Phase 2 Pilot Study of Manualized MDMA-Assisted Psychotherapy in Subjects With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)

Status Completed

Clinical Trial Summary

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop after a traumatic life experience that severely reduces quality of life. This Phase 2 pilot study examined the safety and efficacy of MDMA-assisted psychotherapy in 23 subjects with chronic, treatment-resistant posttraumatic stress disorder (PTSD). This study is part of a global series of Phase 2 pilot clinical trials. This randomized, double-blind, dose response study assessed two active doses of MDMA, 100 mg and 125 mg, to a comparator dose of MDMA (40 mg) during psychotherapy sessions. The initial dose was followed 1.5 to 2.5 hours later by an optional supplemental dose of MDMA that was half the size of the first dose. MDMA was administered in two experimental sessions lasting up to eight hours and scheduled three to five weeks apart. Subjects were prepared for MDMA-assisted psychotherapy prior to the first session in three preparatory sessions, and worked with the same pair of therapists throughout the study. After each MDMA-assisted psychotherapy session, subjects had three integrative sessions with their therapist team to process and understand their experience.

This study assessed the change in symptoms of PTSD, as measured by the Clinical Administered PTSD Scale (CAPS) [Blake et al., 1995], as well as symptoms of depression, as measured by the Beck Depression Inventory II (BDI-II) [Beck, A.T. and R.A, 1984; Beck, A.T., et al., 1996] from baseline enrollment to one month after the second MDMA-assisted psychotherapy session (primary endpoint).

Participants who received the comparator dose of MDMA (40 mg) were given the option to enroll in Stage 2, where they underwent three open-label MDMA-assisted psychotherapy sessions with an active dose of MDMA. People who received either of the active doses of MDMA in Stage 1 had a third MDMA-assisted psychotherapy session with another active dose of MDMA.

Clinical Trial Description

Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop after a person experiences a traumatic event, such as sexual assault, war, or any other life-threatening event. PTSD is a worldwide health problem that severely reduces a person's quality of life and is associated with high rates of psychiatric and medical comorbidity, disability, suffering, and suicide. At least a third of PTSD patients fail to respond to established PTSD psychotherapies. A wider array of effective treatments for PTSD are needed.

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy may be a potential treatment option for PTSD. MDMA is a monoamine releaser that affects serotonin, norepinephrine, and dopamine. MDMA is capable of inducing unique psychopharmacological effects such as decreased feelings of fear, increased feelings of wellbeing, increased sociability and extroversion, increased interpersonal trust, and an alert state of consciousness. In the U.S., MDMA was used as an adjunct to psychotherapy by a considerable number of psychiatrists and therapists before it was placed in Schedule I in 1985 as a result of non-medical use.

This Phase 2 pilot study is a randomized, double-blind, dose response study to examine the safety and efficacy of MDMA-assisted psychotherapy in 23 subjects with chronic, treatment-resistant PTSD of at least six months duration. This study is part of a global series of Phase 2 pilot clinical trials. This study assessed two active doses of MDMA, active dose 1 (100 mg) and active dose 2 (125 mg), to a comparator dose of MDMA (40 mg) during psychotherapy sessions. The initial dose of MDMA was followed 1.5 to 2.5 hours later by an optional supplemental dose of MDMA that was half the size of the first dose. MDMA was administered orally in two experimental sessions lasting up to eight hours and scheduled three to five weeks apart.

Subjects were prepared for MDMA-assisted psychotherapy in three preparatory sessions prior to the first experimental session, and worked with the same pair of therapists throughout the study. After each experimental session, three integrative sessions were scheduled with the subject, including one integrative session the morning after the experimental session. During integrative sessions, subjects processed and connected their thoughts and feelings about the experience with their therapist team.

Subjects who received the comparator dose (40 mg) were given the option to enroll in Stage 2, where they underwent three open-label MDMA-assisted psychotherapy sessions. 100 mg of MDMA was administered in the first session and therapists determined whether to increase to 125 mg of MDMA for the second and third experimental sessions. People who received 125 mg of MDMA during the first two experimental sessions received the same dose during an open-label third experimental session. People who received 100 mg of MDMA during the first two sessions were able to choose, in consultation with their therapist, to either continue to receive 100 mg in a third session or to increase their dose to 125 mg.

A blinded independent rater (IR) assessed the severity of PTSD symptoms at baseline, one month after the second experimental session (the primary endpoint), two months after the third open-label experimental session, and at equivalent points in Stage 2. ;

Related Conditions & MeSH terms

• Posttraumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

• NCT number: NCT01793610
• Study type: Interventional
• Source: Lykos Therapeutics
• Status: Completed
• Phase: Phase 2
• Start date: May 13, 2013
• Completion date: February 1, 2017