MDMA-Assisted Psychotherapy for PTSD

by Charlotte Harrison, Senior Clinical Research Associate, Multidisciplinary Association for Psychedelic Studies (MAPS)
August 10, 2018

MDMA, arguably best known as a “rave” and “party” drug, may be the most effective treatment for post-traumatic stress disorder (PTSD), a debilitating condition affecting at least 8 million adults in the United States within a given year [1]. Preliminary results from clinical trials of MDMA (3,4-methylenedioxymethamphetamine), in combination with psychotherapy, are encouraging for both veterans traumatized by war and others struggling with this disorder. Based on preliminary evidence from Phase 2 trials, in August 2017 the Federal Drug Administration (FDA) granted the program Breakthrough Therapy Designation, acknowledging that it represents a potentially significant advance compared to currently available treatments. People suffering with PTSD deserve a breakthrough, and MDMA-assisted psychotherapy could be it.

PTSD can occur after a person experiences or witnesses a traumatic event (e.g., violence, sexual abuse, war, natural disaster, accidents) and is a serious and disabling mental health condition. Of the 50-60 percent of Americans who experience or witness a significant trauma, 7-8 percent will develop PTSD at some point in their lives. About 10 percent are women and 4 percent men [1]. People with PTSD often suffer from intrusive thoughts and nightmares, increased physical reactivity and startle reaction, difficulty concentrating and sleeping, irritability and negative thoughts. For reasons of self-preservation, people with PTSD often avoid any reminders of, or thoughts about, their trauma, which can make effective participation in traditional talk therapy challenging. They may feel isolated and uninterested in their lives, find it difficult to maintain employment and relationships, and often turn to abusing substances for temporary relief.

Due to the unfortunate reality of warfare trauma, US veterans are more commonly diagnosed with PTSD, with percentages varying by service era. Between 11 and 20 percent of those serving in Operations Iraqi Freedom and Enduring Freedom, and about 12 percent serving in the Gulf War (Desert Storm) have PTSD. Numbers are higher for Vietnam veterans, with about 30 percent diagnosed with PTSD within their lifetime. The US Department of Veterans Affairs (VA) reported a three-fold increase in PTSD-related disability cases, from 345,000 in 2008 to more than 940,000 in 2017 [2]. The VA spends approximately USD $17 billion per year in disability payments to veterans with service-related mental health issues [3], and mental illness costs Americans USD $193 billion annually [4]. But this disorder deprives society of more than just money. Roughly 20.6 US veterans commit suicide every day [5] – one every 70 minutes – and the risk of suicide is two to three times higher for people living with PTSD.

A Short History of MDMA

MDMA has an unusual history. The molecule was first synthesized by the pharmaceutical company Merck in 1912. The company patented MDMA in 1914 but shelved it after limited animal research led to no beneficial discoveries or interesting effects. MDMA was on the list of psychoactive agents studied by the US military during the infamous and unethical MK-ULTRA “mind control” experiments begun in 1953. In 1965 Alexander Shulgin, a biochemist with a PhD from the University of California at Berkeley, resynthesized MDMA – a legal but unregulated compound at the time – and self-experimented with it in 1976. His experiences of euphoria and self-love led him to believe MDMA would be useful in psychotherapy, so he shared the drug with Leo Zeff, an Oakland, Calif., psychologist and psychotherapist, who found it especially helpful for couples’ therapy. Use of MDMA in therapy spread quickly, and about 500,000 doses were used therapeutically during the 1970s and 80s.

As recreational use of MDMA increased, the Drug Enforcement Administration (DEA) took notice. In 1985, despite considerable testimony about MDMA’s therapeutic benefits, DEA placed it on Schedule I, a drug classification with high potential for abuse, no accepted medical use and lacking safety information. MDMA continues to be used recreationally, especially at parties and music events, but it is commonly adulterated with other drugs and sold as “Ecstasy” or “Molly,” which often contain no MDMA at all. Addition of other substances, which are generally not disclosed to the user, and used in uncontrolled, overheated and crowded environments, can add significant risk.

An Alternative to SSRIs

In Spain in 2000, the US-based, non-profit Multidisciplinary Association for Psychedelic Studies (MAPS) initiated the first double-blind, placebo-controlled clinical trial to assess MDMA-assisted psychotherapy as a treatment for PTSD. After the Spanish trial was shut down by Spanish regulatory authorities for political reasons, MAPS completed six others globally, including three in the United States and one each in Switzerland, Canada and Israel. Participants in these early studies had severe, chronic, treatment-resistant PTSD. The average person suffered for 17.8 years before participating in the study, and other treatments had already failed. Of those who received the active dose of MDMA across the six, Phase 2 clinical trials, after completing treatment 56 percent no longer met the diagnostic criteria for PTSD. A year later, with no additional sessions, 68 percent of participants no longer qualified for a PTSD diagnosis.

On May 1, 2018, results of MAPS’ second-largest Phase 2 trial, which only enrolled military veterans, firefighters and police officers with PTSD, were published in the prestigious peer-reviewed journal The Lancet Psychiatry. Study participant and US Army/Marine veteran Jonathan Lubecky told RedState.com [6], “I cannot emphasize how much this treatment changed my life. I went from constant, daily suicidal ideation, anxiety and depression to almost nothing. The best part was this was not lifelong treatment and medication.”

Current medications for PTSD are insufficient. If a person is diagnosed with PTSD today, the two medications approved for treatment are antidepressant selective serotonin reuptake inhibitors (SSRIs) sertraline (Zoloft) and paroxetine (Paxil). Results of clinical trials for Zoloft found a reduction in PTSD symptoms for women only; the drug was not demonstrated to be efficacious in men [8-9]. Many patients prescribed SSRI treatment need to continue their use after the initial 12-week treatment period. SSRIs approved for PTSD can have uncomfortable side effects, and since these are daily medications, many people struggle with them continuously.

When SSRIs are discontinued, patients can suffer serious and challenging withdrawal effects, and PTSD symptoms often reappear. The number of people still receiving disability benefits for PTSD demonstrates that many patients continue to meet the criteria for the diagnosis even after extended SSRI treatment. Other options for PTSD treatment can include Prolonged Exposure therapy, Eye Movement Desensitization and Reprocessing, talk therapy, and yoga, which can be helpful for many patients but not all. Further research will need to be done to see if MDMA can enhance existing psychotherapies.

 

MDMA-assisted psychotherapy may treat the root cause of PTSD by providing patients a window through which they can access and heal their trauma.

MDMA Effects & Inner Healing

The pure form of MDMA, which is used in clinical trials, can foster a sense of safety when used in a comfortable, controlled environment. During a therapeutic session, participants are often able to recall and process their trauma more effectively and safely because of MDMA’s ability to decrease fear and anxiety responses. Empathy, interpersonal trust and self-compassion are heightened, thus creating a supportive environment for psychotherapy for PTSD. Rather than managing symptoms, MDMA-assisted psychotherapy may treat the root cause of PTSD by providing participants a window through which they can access and heal their trauma.

Effects of MDMA usually begin about 30 minutes to one hour after administration and last three to six hours. If an optional supplemental dose is taken (usually about one-half the initial dose) around two hours into the session, effects can be extended to five to eight hours. MDMA is not without side effects, but in Phase 2 results reactions were generally mild, not of clinical concern and resolved within a few days. Common reactions in clinical settings include anxiety, fatigue, headache, jaw clenching, lack of appetite and nausea, though most of these reactions stop when the drug’s effects wear off. MDMA also causes a transient increase in heart rate and blood pressure, which can be unsafe for people who have hypertension or a history of cardiac illness but is comparable to moderate exercise for healthy people. MDMA also causes an increase in body temperature, which can be dangerous in uncontrolled environments like nightclubs but has been mild and not medically significant in a clinical context.

Significantly, in contrast to SSRI treatment for PTSD, which must be taken every day to be effective, MDMA-assisted psychotherapy protocols require only three treatment sessions about one month apart. Participants have many hours of non-drug psychotherapy to help them prepare for the sessions and integrate their experience following. But after taking the drug only three times, two-thirds of participants in Phase 2 trials experienced a durable remission from PTSD one year following the last treatment. Unlike SSRI treatment, MDMA does not require daily maintenance treatment and does not have to stay in the body system for lasting effects. MAPS’ goal is for MDMA-assisted psychotherapy to become another tool available to patients who are not significantly helped by standard therapies or who could benefit from an alternate method of treatment.

Protocols require extensive medical and psychiatric screening to ensure treatment will be safe for the participant. If eligible, participants undergo three 90-minute preparatory sessions to discuss their trauma, to build the therapeutic alliance between therapists and participant, and to prepare for dosing sessions. Each of the three, eight-hour experimental sessions, spaced about one month apart, is followed by a comfortable overnight stay at the study site and a non-drug, 90-minute integration session the following morning. Throughout the next few weeks, two more integration sessions occur before the next MDMA-assisted session. Total therapy time for a participant is more than 40 hours. At the beginning, during and end of the study, an independent rater, who is unaware of whether the participant was assigned to placebo or MDMA, conducts an assessment of their PTSD using the Clinician-Administered PTSD Scale (CAPS), the gold standard for clinical trials. In Phase 2 studies, the mean reduction in score on the CAPS was 47.3 points. In comparison, trials of Zoloft and Paxil produced only a 6 to 14 point drop [8-9].

The therapy itself is unique in its non-directive nature. Therapists are present to support the participant’s healing process, which is largely self-initiated. The training manual discusses each individual’s “inner healing intelligence,” which can be accessed effectively with MDMA. Therapists create and hold a safe space for participants to reflect inward and to listen to the deepest, wisest parts of themselves, where they often find self-love and compassion – a place generally difficult to access for many years due to the nature of their PTSD symptoms. Often, several session hours will be spent with the participant wearing eyeshades and listening to music in an extended period of introspection. The wisdom and sensations from these sessions are discussed at length in non-drug integration sessions, where the participant works to merge the experience into their normal, daily life. Many therapists and participants have noted that insights and healing, which can take years in traditional talk therapy, can happen in one MDMA-assisted session, provided proper steps are taken to prepare and to integrate.

 

FDA completed a Special Protocol Assessment of the study design for Phase 3 trials and agreed that plans for the study are scientifically valid, and results, if positive, will lead to approval.

Next Steps with FDA Support

The next step for MDMA-assisted psychotherapy is Phase 3 clinical trials, which aim to reproduce the Phase 2 trial results in addition to collecting more safety data in a larger population. MAPS plans to enroll at least 200 participants in these global studies, scheduled to begin August 2018 at 15 sites in the United States, Canada and Israel. MAPS has developed an extensive therapist training program with experienced and pioneering therapists, such as Michael Mithoefer, Annie Mithoefer, Marcela Ot’alora and Shannon Carlin. Therapist teams are comprised of one male and one female therapist to provide optimum comfort and support for participants. So far, 44 therapy teams have been selected to conduct the next step of the research.

FDA has been supportive of MAPS’ program to study the effects of MDMA-assisted psychotherapy. In July 2017, FDA completed a Special Protocol Assessment (SPA) of the study design for Phase 3 trials. It agreed that plans for the study are scientifically valid and results, if positive, will lead to approval. Based on preliminary evidence from Phase 2 trials, FDA granted the program Breakthrough Therapy Designation in August 2017 and acknowledged that it represents a potentially significant advance compared to currently available treatments. FDA will expedite reviews, provide guidance on the drug development program, and commit to frequent meetings and communication with MAPS, the study sponsor. Current timelines estimate MAPS will seek agency approval by 2021.

Psychedelic medicine could shift the field of psychiatry from management of symptoms through lifelong medication to addressing root causes of suffering through safe, controlled use of specific drugs to assist therapy. In addition to alleviating PTSD, MDMA-assisted psychotherapy is also being studied for alcohol use disorder, anxiety associated with life-threatening illness and social anxiety in adults on the autism spectrum. Other researchers are focusing efforts on other psychedelic substances like ketamine and ayahuasca for depression, and ibogaine for opiate addiction. The Usona Institute’s Phase 3 studies for depression using psilocybin (the active ingredient in magic mushrooms) are planned to begin in 2018. Most of these researchers were among the 3,500 people in attendance when MAPS hosted the Psychedelic Science 2017 conference in Oakland, Calif., April 2017. This growing field of academics, therapists and researchers is committed to learning about these potential medicines and obtaining scientifically valid data on their efficacy and safety.

MAPS’ vision is to open MDMA-assisted psychotherapy centers throughout the United States and the world for those suffering from PTSD. To ensure quality and safety, MAPS is preparing to train and certify therapists to conduct this therapy post-approval, just as therapists are now trained extensively for clinical trials. MAPS is looking ahead and working closely with federal and local regulatory agencies to complete these trials, and if they are successful, to ensure the treatment is widely accessible. This includes seeking coverage by insurance companies and federal health care. If proven effective in Phase 3 trials, this treatment could be the breakthrough veterans and many others with PTSD desperately need to heal.

 

Multidisciplinary Association for Psychedelic Studies (MAPS) was founded in 1986 as a 501(c)(3) non-profit research and educational organization. It develops medical, legal and cultural contexts for people to benefit from careful use of psychedelics and marijuana. Since its founding, MAPS has raised more than $47 million for psychedelic therapy and medical marijuana research and education. As a non-profit with no government funding for psychedelic research, MAPS relies on contributions from individuals, businesses and foundations. MAPS-sponsored clinical trials are conducted by MAPS Public Benefit Corporation (MPBC), a wholly owned subsidiary of MAPS formed in 2015 for the purpose of balancing social benefits with income from legal sales of MDMA, other psychedelics and marijuana. For more information, visit maps.org.

Image Credit: iStock/spukkato

 

References:

  1. VA NCPTSD 2017
  2. Statement of Jon A. Wooditch, Acting Inspector General Department of Veterans Affairs, in Committee on Veterans’ Affairs Subcommittee on Disability Assistance and Memorial Affairs. 2005: Washington, DC
  3. Solon, O., My therapist gave me a pill: Can MDMA help cure trauma? https://www.theguardian.com/society/2016/sep/16/mdma-ptsd-therapy-trauma-maps-medical-study#comments, The Guardian. 2016.
  4. NAMI
  5. https://www.mentalhealth.va.gov/docs/data-sheets/OMHSP_National_Suicide_Data_Report_2005-2015_06-14-18_508-compliant.pdf
  6. https://www.redstate.com/jmlubecky/2016/11/16/cure-ptsd/
  7. https://link.springer.com/epdf/10.1007/s00213-017-4779-2?author_access_token=StczFuKkfkhR-C_mhKgxSPe4RwlQNchNByi7wbcMAY5RwD-v69hSM1Tc5L_FYZ9jerQj-vgn5oSAUAiYZTGNwmpXgFjLulSA2nlXqHu_YpnYh4zhpcmiuhcuffmHwG6B8ha4sOlDqB6uM4d7vs6IYQ%3D%3D
  8. Brady, K., et al., Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA, 2000. 283(14): p. 1837-44.
  9. Davidson, J.R., et al., Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry, 2001. 58(5): p. 485-92.

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