MDMA for PTSD and Alcoholism
(MDMA Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Carolina L Haass-Koffler
Must not be taking: Antidepressants, Antipsychotics
Disqualifiers: Liver disease, Hypertension, Arrhythmia, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
The study investigators are conducting the first open label pilot trial of MDMA-assisted therapy (MDMA-AT) with a comorbid sample of military veterans with a comorbid diagnosis of Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD). This novel experimental treatment package consists of two once-monthly Experimental Sessions of therapy combined with a divided-dose of MDMA HCl, along with non-drug preparatory and integrative therapy. The Primary Outcome measure, the Timeline Follow-back (TLFB), will evaluate changes in alcohol use over time. Changes in PTSD symptoms will also be evaluated.
Will I have to stop taking my current medications?
The trial requires participants to taper off antidepressant medications before starting the study. If you are on SSRIs, you need approval from a physician to taper off. Other psychiatric medications and certain medications that prolong the QT interval are also not allowed during the study.
What data supports the effectiveness of the drug MDMA for PTSD and Alcoholism?
Is MDMA safe for use in humans?
MDMA has been studied for its use in treating PTSD, but it can increase blood pressure, heart rate, and body temperature. There is a risk of serotonin syndrome, especially when combined with other drugs, but no cases have been reported in clinical trials where MDMA was the only drug taken. Other potential risks include liver damage and cardiovascular events.678910
How is the drug MDMA unique in treating PTSD and alcoholism?
MDMA is unique because it is used as a catalyst in psychotherapy, helping to treat PTSD by affecting brain regions like the amygdala and hippocampus, which are involved in emotional processing. Unlike traditional treatments, MDMA-assisted therapy has shown promise in treatment-resistant cases by enhancing the therapeutic process.3461112
Research Team
Eligibility Criteria
This trial is for military veterans who have both Alcohol Use Disorder (AUD) and Post-Traumatic Stress Disorder (PTSD). Participants must be fluent in English, able to prove veteran status, meet specific criteria for AUD and PTSD with a certain severity of symptoms, can abstain from alcohol safely for 48 hours without medical detox, are capable of swallowing pills, and agree to recorded study visits. They also need a contact person available for emergencies.Inclusion Criteria
I have agreed with my care team on a plan to manage my symptoms without self-medicating.
I have been diagnosed with PTSD and my severity score is 28 or higher.
I have Hepatitis C but it doesn't cause symptoms and I've been treated for it.
See 27 more
Exclusion Criteria
Current Personality Disorders assessed via the SCID-5-PD
Lack of social support or stable living situation
Sensitivity to any of the study interventions or components thereof
See 23 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Preparatory Therapy
Participants engage in non-drug preparatory therapy sessions
4 weeks
Treatment
Participants receive two once-monthly Experimental Sessions of MDMA-assisted therapy
8 weeks
2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments and optional imaging
6 weeks
Treatment Details
Interventions
- MDMA (Other)
Trial OverviewThe trial is testing MDMA-assisted therapy as a new treatment approach for veterans with AUD/PTSD comorbidity. It involves two monthly sessions where therapy is combined with divided doses of MDMA HCl. The main focus is on changes in alcohol use over time and improvements in PTSD symptoms.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: MDMA-ATExperimental Treatment1 Intervention
Participant will receive MDMA administration with assisted therapy (AT) by trained clinicians
MDMA is already approved in United States for the following indications:
🇺🇸 Approved in United States as MDMA for:
- Posttraumatic stress disorder (PTSD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brown UniversityProvidence, RI
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Who Is Running the Clinical Trial?
Carolina L Haass-Koffler
Lead Sponsor
Trials
1
Patients Recruited
20+
Carolina Haass-Koffler
Lead Sponsor
Trials
1
Patients Recruited
20+
References
MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study. [2023]Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation. Appeared originally in Nat Med 2021; 27:1025-1033.
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. [2023]Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P
A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis. [2022]Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials.
The Psychopharmacology of ±3,4 Methylenedioxymethamphetamine and its Role in the Treatment of Posttraumatic Stress Disorder. [2015]Prior to 1985, ±3,4-methylenedioxymethamphetamine (MDMA) was readily used as a psychotherapeutic adjunct. As MDMA became popular in treating various psychiatric illnesses by mental health professionals, the public started to abuse the MDMA-containing recreational drug "ecstasy." This alarmed the DEA, which led to emergency scheduling of MDMA as a Schedule I drug. Due to its scheduling in 1985, human research and clinical use has been limited. The majority of research on MDMA has been focused on the drug's potential harmful effects rather than its possible therapeutic effects. The limitations on retrospective human studies and preclinical animal models of MDMA neurotoxicity are examined in this analysis. New research has shown that MDMA, used as a catalyst in psychotherapy, is effective in treating posttraumatic stress disorder (PTSD). This review also examines the psychopharmacological basis for the efficacy of MDMA-assisted psychotherapy. Specifically, the brain regions involved with both PTSD and those activated by MDMA (i.e., amygdala, anterior cingulate cortex, and hippocampus) are examined. Also, the possible neurochemical mechanisms involved in MDMA's efficacy in treating PTSD are reviewed.
3,4-Methylenedioxymethamphetamine's (MDMA's) Impact on Posttraumatic Stress Disorder. [2019]Review the current literature assessing the role of 3,4-methylenedioxymethamphetamine (MDMA) on posttraumatic stress disorder (PTSD).
Prevalence and Correlates of Past Year Ecstasy/MDMA Use in the United States. [2023]3,4-Methylenedioxymethamphetamine (MDMA) (also known as "ecstasy" or "Molly") has regained attention in recent years for its efficacy in treating posttraumatic stress disorder, and the drug was granted breakthrough therapy designation for such use by the US Food and Drug Administration in 2017. However, little is known about the current epidemiology of recreational ecstasy/MDMA use.
In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation. [2021]Recent clinical studies support the use of 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct treatment for posttraumatic stress disorder (PTSD). Despite these promising findings, MDMA administration in controlled settings can increase blood pressure, heart rate, and body temperature. Previous studies indicate thatO-demethylated metabolites of MDMA contribute to its adverse effects. As such, limiting the conversion of MDMA to reactive metabolites may mitigate some of its adverse effects and potentially improve its safety profile for therapeutic use.
Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database. [2022]3,4-Methylenedioxymethamphetamine (MDMA), is investigated as a treatment for post-traumatic stress disorder and other anxiety-related conditions in multiple placebo-controlled and open label studies. MDMA-assisted therapy is projected for approval by the United States Food and Drug Administration (FDA) and other regulatory agencies worldwide within the next few years. MDMA is a monoamine releaser and uptake inhibitor affecting serotonin, potentially increasing the risk of serotonin syndrome (SS). No instances of SS have occurred in clinical trials. The relatively small number of patients in controlled trials warranted a survey of FDA Adverse Event Reporting System data for the occurrence of SS in a larger database. We found 20 SS cases in people exposed to MDMA, all of which had also taken one or more substances with serotonergic properties in addition to MDMA, including amphetamines, stimulants, and opioids. There were no cases of SS associated with MDMA where MDMA was the sole reported compound taken.
The Efficacy of MDMA (3,4-Methylenedioxymethamphetamine) for Post-traumatic Stress Disorder in Humans: A Systematic Review and Meta-Analysis. [2021]Background: 3,4-methylenedioxymethamphetamine (MDMA), known recreationally as "Molly" or "Ecstasy", is a triple monoamine reuptake inhibitor. MDMA specifically acts as a weak 5-HT1 and 5-HT2 receptor agonist, targeting 5-HT2A, 5-HT2B, and 5-HT2C receptors. Its potential use for therapeutic purposes with these pharmacological profiles remains a controversial subject. Studies have shown the potential benefits in clinical trials for post-traumatic stress disorder (PTSD). A larger amount of data has been provided for the push in support of MDMA-assisted psychotherapy in these patients.  Objective: The aim of this article is to compute a meta-analysis and conduct a systematic review of the effects of MDMA on PTSD, discussing the potential benefits and adverse events relative to dosing and stability of treatment. Methods: Articles were collected and analyzed for systematic review: 16 articles were included in the systematic review that met the criteria for the use of MDMA in the treatment of PTSD as well as assessing the safety and efficacy of the drug in human participants. Ten studies were used for the meta-analysis, with a cumulative sample size of 168 patients. The significance of the findings on dosing and efficacy of MDMA in healthy human participants was quantified based on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and PTSD symptom scores. Results: The disorders for which MDMA demonstrated a net positive or net negative effect on symptoms are presented separately. Adverse events in patients across all disease classes are presented. The therapeutic index for patients who demonstrated a benefit is also presented. An odds ratio for beneficial and adverse events is used to determine treatment-resistant patients who may benefit from clinical trials of MDMA. Discussion: Findings show promising evidence for the potential therapeutic use of MDMA alongside psychotherapy in the treatment of PTSD. The pharmacological profile of MDMA may provide direction for future drug developments to treat patients with treatment-resistant psychiatric disorders.
How MDMA's pharmacology and pharmacokinetics drive desired effects and harms. [2019]3,4-Methylenedioxymethamphetamine (MDMA) is an agent of abuse that has been used by over 16 million Americans. Increased energy, elevated mood, bonding with others, and psychedelic effects are desired effects while liver damage, extended depressed mood, sexual assault, rhabdomyolysis, serotonin syndrome, multiorgan failure, cardiovascular events, arrhythmias, and death are possible adverse effects. These desirable and adverse effects of MDMA are extensions of its fascinating pharmacologic and pharmacokinetic profile. In addition to methamphatemine like effects, MDMA also has mescaline like effects and increases the release of cortisol, oxytocin, and antidiuretic hormone. The desirable effects of MDMA are accentuated by the rave or electronic dance music scene where warm temperatures, vigorous dancing, loud music, and light shows accentuate some of the responses. However, the same environment increases the risk of certain harms. Knowledge of the constellation of these factors is needed for education, prevention of harm, and treatment.
MDMA does not alter responses to the Trier Social Stress Test in humans. [2018]±3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a stimulant-psychedelic drug with unique social effects. It may dampen reactivity to negative social stimuli such as social threat and rejection. Perhaps because of these effects, MDMA has shown promise as a treatment for post-traumatic stress disorder (PTSD). However, the effect of single doses of MDMA on responses to an acute psychosocial stressor has not been tested.
Psychiatric disorders in Ecstasy (MDMA) users: a literature review focusing on personal predisposition and drug history. [2019]3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) has been implicated in the onset of a number of psychological disorders and associated with a number of psychiatric symptoms that have persisted after cessation of the drug. This paper is a review of the published psychiatric case studies from the last 10 years involving MDMA. Only 24% of patients had a previous psychiatric history and 34% had a psychiatric illness amongst first degree relatives. The percentage of patients not having had a personal or family history of psychiatric illness and the temporal relationship between MDMA ingestion and the experience of recurring symptoms strongly suggest a causal relationship between the drug and neuropsychiatric manifestations. Further supporting evidence comes from several studies using non-clinical samples. Ecstasy users that don't present themselves in healthcare settings as having clinical symptoms have significantly higher scores on certain subscales of the SCL-90 compared with Ecstasy-naive controls, with higher pathology scores in heavier Ecstasy users. The full-blown psychiatric cases may represent the broad end of this problematic spectrum. Copyright 2001 John Wiley & Sons, Ltd.