The past decade has seen numerous clinical trials focused on the medicinal and psychological benefits of psychedelics. The results couldn’t be more promising, and yet the next steps of psychedelics are the most crucial. Psychedelics are still registered as Schedule 1 substances, despite evidence that they are neither addictive nor widely abused.
This restriction means that psychedelic-assisted therapy and other treatments are withheld from patients. Red tape, paranoia, and outdated stigma have kept medicine from those who need it most.
Change is in the air, though. There has been a ton of buzz in the news about MDMA therapy—and rightly so. As the researchers and clinicians reach the next steps in the slow march toward regulatory approval, you might be wondering: what does MDMA-assisted therapy do, and what could it do for me?
In this post, we’ll cover:
- What MDMA is, the pharmacology of MDMA, and how it works in a mental health setting
- How health care researchers are researching MDMA treatment in clinical settings and pushing toward legal access to the drug through the US Food and Drug Administration (FDA)
- MDMA reaching the next step toward approval and what is coming in the future
And more! So let’s get started…
What is MDMA?
MDMA (3,4-methylenedioxymethamphetamine) is a synthetic compound that alters perception and mood. It belongs to the class of psychoactive drugs known as entactogens, which means “touching within.”
In terms of psychopharmacology, MDMA is chemically similar to hallucinogens such as psilocybin or ketamine. It is also similar to stimulants such as ecstasy and cocaine. MDMA produces feelings of increased emotional warmth, pleasure, and energy, as well as a distorted perception of time and sensory input.
MDMA works by increasing the activity of three neurotransmitters in the brain: serotonin, dopamine, and norepinephrine. It primarily stimulates the release of serotonin, a neurotransmitter that regulates mood, social behavior, appetite, sleep, and other functions. MDMA also causes the release of oxytocin, a hormone that plays a role in social bonding and trust.
Post-Traumatic Stress Disorder (PTSD) and MDMA-Assisted Psychotherapy
For context, post-traumatic stress disorder (PTSD) is notoriously difficult to treat. The disorder affects roughly 8 million adults any given year. Many patients who are resistant to traditional treatment have little recourse. In fact, it’s been 17 years since the release of the last new medication for this disorder.
PTSD damages relationships, careers, and wellbeing. It often causes increased depression, which in some tragic cases, leads to suicide.
Psychotherapy is a partnership between therapist and patient, one that depends on trust, candidness, vulnerability, and an open mind. The problem is that PTSD often causes distrust and defensive tendencies. Deeply ingrained fear responses can keep the walls up, making it difficult to process the root of traumatic experiences. Psychological healing can be very challenging under these circumstances.
What is MDMA Therapy?
MDMA therapy is a form of psychotherapy that uses MDMA as an adjunct to treatment. It involves the administration of a single dose of MDMA in a controlled setting with the guidance of trained therapists. The therapy typically involves two or three sessions.
The psychotherapy sessions last for about 6-8 hours. Patients ingest the MDMA and begin with relaxing breathwork guided by psychotherapists.
During an MDMA therapy session, the patient takes the drug and then engages in talk therapy with the therapy team. Two specially trained therapists guide the session – generally a male and a female, a recommended arrangement for those with childhood trauma.
The patient spends much of the session reclined, listening to music and going within. The next steps include therapeutic and supportive conversation.
The therapy is designed to help the patient explore and process difficult emotions, traumatic experiences, and other psychological issues. The effects of MDMA can help the patient feel more open, empathetic, and connected, which can facilitate deeper insights and emotional breakthroughs.
MDMA is a known catalyst for profound breakthroughs and insights into the self. In a therapeutic setting, it raises awareness of different aspects of the psyche. This allows patients to safely explore difficult mental and emotional states with clarity and compassion.
Therapists involved in these trials report that many patients come to unprompted breakthroughs and epiphanies on their own. The participants themselves have likened MDMA to an “inner healer”, or a spring cleaning of the mind. It gives patients the courage and space to deal with traumatic memories and process deep-seated fears.
How does MDMA-assisted therapy help push patients through the hurdle of recovery in a physiological sense? MDMA combats the distrust, defensive tendencies, and deeply ingrained fear responses created by traumatic experiences by releasing serotonin, norepinephrine, and dopamine into the system, as well as increasing neurohormones oxytocin levels. It accelerates emotional processing and lowers activity in the amygdala, the part of the brain responsible for processing fear.
This cocktail of reward system chemicals reduces defensive responses while enhancing compassion, social connection, and introspection. Patients are more likely to trust therapists and engage with deep internal processing around their fears and trauma.
[For more on the potential uses of MDMA-assisted psychotherapy, see this Rick Doblin interview]
Phases of MDMA Therapy
MDMA therapy is currently being studied as a potential treatment for a variety of mental health conditions, including PTSD, anxiety, depression, and addiction. An MDMA-assisted therapy session typically involves a preparation phase, the session itself, and an integration phase.
In the preparation phase, the therapist or team of therapists will work with the patient to establish a relationship of trust and safety. They will discuss the goals of the therapy, the patient’s medical history, and any potential risks or side effects of the treatment. The patient may also be given some tasks to complete before the session to help them prepare mentally and emotionally.
During the sessions, the patient takes the doses of MDMA under the supervision of the therapists. The effects of the drug typically start within 30-45 minutes and can last for up to six hours. During this time, the patient engages in talk therapy with the therapists.
The therapist may encourage the patient to explore their emotions, thoughts, and memories, and to focus on the present moment. The therapist may also use techniques like guided meditation, music, or art to help the patient connect with their feelings and thoughts.
The experience of an MDMA-assisted therapy session can vary depending on the individual and their specific needs. Some patients may feel a sense of euphoria, relaxation, or openness. They may experience a heightened sense of empathy and connection with others and reduced defensiveness. Others may experience difficult emotions or memories that need to be processed with the help of therapists.
After the session, the patient enters the integration phase. This is when the patient works with the therapists to integrate the insights and experiences from the session into their daily life. The therapists may help the patient create a plan for ongoing self-care and support, and may offer additional therapy sessions as needed.
It’s important to note that MDMA-assisted therapy should only be conducted under the guidance of trained therapists in a controlled setting.
Science of MDMA
The scientific research on MDMA for PTSD and depression is in a blossoming stage. There is growing evidence that suggests it may be a promising treatment option.
MDMA was first used in couples therapy with success. In this context a variety of symptomologies may present and multiple treatment modalities may be used.
Studies have shown that MDMA-assisted therapy can be effective in reducing symptoms of severe PTSD, treatment-resistant PTSD, and other patients who have not responded to traditional therapies.
For example, a phase 2 clinical trial found that MDMA-assisted therapy was associated with significant improvement in PTSD symptoms in veterans, firefighters, and police officers with chronic PTSD. There is also evidence that MDMA treatment produces significant improvement in eating disorder symptoms among adults with a PTSD diagnosis.
[For a recent meta-analysis on MDMA and PTSD see Mitchell et al at DOI: 10.1002/jcph.1995]
There is also some evidence that MDMA-assisted therapy may be helpful in treating depression. A study published in 2020 found that MDMA-assisted therapy was associated with significant reductions in symptoms of depression in patients with life-threatening illnesses.
The nonprofit organization Multidisciplinary Association for Psychedelic Studies (MAPS Public Benefit Corporation, MAPS PBC, or just MAPS) is soon to complete its multi-site Phase 3 trials on MDMA-assisted psychotherapy for PTSD. It follows the success of their Phase 2 trials, which showed groundbreaking results.
The MAPS MDMA research team recruited 105 participants with severe PTSD. The majority of subjects had attempted various treatments in the past, without lasting success.
After receiving just three sessions of MDMA-assisted psychotherapy, the subjects reported incredible improvements to their mental health. 12 months on, 68% no longer suffered any symptoms of PTSD.
Follow-up studies over three years later confirmed that the results were long-lasting. The evidence is clear. MDMA-assisted psychotherapy represents the next steps of psychedelic treatment, and is more effective than any other for PTSD.
With this and other MDMA Phase 3 trials in the final stretch, the results will likely be just as statistically significant. Once the numbers are confirmed, the FDA will approve MDMA-assisted psychotherapy for PTSD treatment.
Current Legal Status
In the United States, MDMA is classified as a Schedule I drug under the Controlled Substances Act, meaning it is considered to have a high potential for abuse and no currently accepted medical use. This classification makes it difficult for researchers to conduct clinical trials and for patients to access the drug for therapeutic purposes.
However, the FDA has granted breakthrough therapy designation to MDMA-assisted treatment of PTSD, which is a recognition of the potential therapeutic benefit of the treatment. This designation allows for an expedited development and review process for drugs that may offer significant benefits over existing treatments.
The FDA has also authorized several clinical trials of MDMA-assisted therapy for PTSD, which are being conducted under the guidance of trained therapists in a controlled setting. These trials are intended to gather evidence on the efficacy and safety of this type of psychedelic-guided psychotherapy, with the goal of potentially gaining FDA approval for it in the future.
Additionally, through the expanded access program, which allows patients to receive investigational MDMA therapy although it is not yet FDA-approved for use outside clinical trials, certain patients with life-threatening conditions or other very serious issues without any other promising options or ongoing clinical trials may be able to receive MDMA. The only eligible sites in the FDA Expanded Access Program are located within the U.S and U.S territories.
California has recently attempted—unsuccessfully—to decriminalize magic mushrooms containing psilocybin as well as other psychedelics throughout the state. Although the measure failed, the state remains on the cutting edge in this area, with psychedelic therapy of various kinds available at multiple sites. And since both Oakland and Santa Cruz have decriminalized all psychedelics, many of these facilities are focused around these areas.
MDMA’s Next Steps Toward Approval
MAPS is currently working through the final rigorous stages of the Phase 3 trials. After successful Phase 3 trials, clinical data goes to the FDA and other governing bodies worldwide for review and, eventually, approval and the market. Their priority now is to confirm the efficacy and safety of the treatment, the last step toward obtaining MDMA FDA approval.
The final studies are double-blind, placebo-controlled randomized trials taking place across the US, Canada, and Israel. The coronavirus pandemic delayed the trials, but 90 of the 100 subjects have already completed the process. Still, the FDA is working with MAPS to ensure approval as soon as possible.
A recent third-party analysis of the data collected so far revealed a 90% probability that the results will be successful. Put simply, MAPS is well on its way to meeting the FDA’s requirements.
Future MDMA Research
These trials represent the future of MDMA-assisted therapy and psychedelics and are bound to open the gates to further legalization, normalization, and patient access. MAPS aims to commercialize the treatment soon, a milestone few had dreamed of prior to these trials. It’s even estimated that psychedelics will be available and free via the NHS in the UK by 2030, ushering in a new era for mental health treatment.
More broadly, the future of MDMA psychedelic research is likely to be characterized by ongoing exploration of the therapeutic potential of the drug, as well as efforts to better understand its mechanisms of action and potential risks.
As the field evolves, the future of research in MDMA-assisted therapy is likely to focus on several key areas, including:
Continued exploration of MDMA-assisted therapy for PTSD and other mental health conditions. As research on the efficacy and safety of MDMA therapy continues to accumulate, there will likely be more studies aimed at expanding its use to other mental health conditions, such as anxiety, addiction, and depression.
Investigation of the neurobiological mechanisms of MDMA. Researchers will continue to explore how MDMA affects the brain and how it can be used to treat mental health conditions. This may involve studies on the molecular and cellular mechanisms of MDMA action, as well as investigations into the long-term effects of the drug on the brain.
Development of new treatment protocols. As researchers learn more about the optimal conditions for MDMA-assisted therapy, they may develop new treatment protocols that are tailored to specific patient populations or that incorporate different therapeutic approaches for use in psychiatry.
Assessment of the risks and benefits of MDMA. While early studies have shown promising results for MDMA-assisted therapy, more research is needed to fully understand the risks and benefits of the treatment. Researchers will likely continue to study the potential long-term effects of MDMA on the brain and body, as well as potential interactions with other medications and substances.
Final Thoughts on MDMA Therapy
Now that MDMA-assisted therapy is so close to approval, the outlook for people with severe PTSD, treatment-resistant depression, and other seriously challenging mental health issues is brighter. Where before it seemed like there were few, if any, options, a faster, more promising choice may be on the horizon.