How Does MDMA Help Patients With PTSD, And Which Pharmaceutical Companies Are Leading The Way For The Coming Revolution In Therapy?

“The biology of PTSD is one of the body changing to accommodate a new reality” states Dr. Rachel Yehuda in a February 2021 interview for ‘The Psychedelic Therapy’ podcast. She holds the position of Director of the Traumatic Stress Studies Division at the Mount Sinai School of Medicine and Vice Chair for Veterans Affairs in the psychiatry department, and she means what she says quite literally. Dr. Yehuda was among the first of a group of scientists studying the hormonal effects of posttraumatic stress disorder in the eighties, and she says one of the most valuable takeaways from this period of her research was proof that “there are biologic changes, there are brain changes, and there are molecular changes, and these things are real.” MDMA’s potential to reverse these changes is what has Dr. Yehuda, and others in the field of PTSD research so excited.

Before PTSD was added to the Diagnostic Statistical Manual of Mental Disorders (DSM-III) in 1980, common wisdom maintained that stress was a temporary condition and that once stressors were removed from the environment, the body would relax. The key insight came, says Dr. Yehuda, in understanding that if you have PTSD “the environment is not triggering you because you’re under chronic stress, you’re under chronic stress because the environment is triggering you.” In other words, the stress response that a person will experience while undergoing a traumatic experience is a different mechanism than the process that sustains a stress response in patients with PTSD. The inability to ascribe meaning to a traumatic event can lock a person into reliving the memory and separate them from their present reality. Bringing them back to the present proves much tougher than it might at first appear.

Epigenetics and PTSD

The type of biological changes Dr. Yehuda talks about in the interview run deep. It seems PTSD can change the way our DNA works through a process named epigenetics. A review of 89 studies published in Biological Psychology Journal, asserts “Posttraumatic stress disorder (PTSD) is a stress-related psychiatric disorder that is thought to emerge from complex interactions among traumatic events and multiple genetic factors. Epigenetic regulation lies at the heart of these interactions and mediates the lasting effects of the environment on gene regulation.”

Most studies focus on observing an epigenetic process known as methylation. According to the CDC website, “DNA methylation works by adding a chemical group to DNA. Typically, this group is added to specific places on the DNA where it blocks the proteins that attach to DNA to “read” the gene. This chemical group can be removed through a process called demethylation. Typically, methylation turns genes “off” and demethylation turns genes “on.” Epigenetic changes happen during an individual’s lifetime but can be passed on to their children and become part of their genetic code. This discovery feels like macabre proof of the sentiment many people with PTSD express, that the person they were before their traumatic event is no more. It also has implications on the macro scale.

Among the many aspects of PTSD that Dr. Yehuda studies are intergenerational trauma and racial trauma. Science is on the way to proving major historical moments can change an entire population’s gene expression for generations. It’s worth remembering that roughly 40 years ago, PTSD wasn’t even recognized as a real disorder, and now we see its effects at every level of society. Suppose researchers were able to devise a form of therapy that could help a majority of PTSD sufferers. In that case, the therapy may be used to help people suffering from these other forms of trauma, detangling their DNA from a narrative of oppression to one of individual freedom.

It is, of course, too early to dwell on such fanciful ideas, but MDMA appears to be able to repair the genetic code in terms of neurobiology, and institutions are making plans for the implementation of MDMA-assisted therapy within the decade, so change may be coming sooner rather than later. MDMA continues to be designated Schedule 1 – that is, “The drug or other substance has no currently accepted medical use in treatment in the United States.” On the plus side, the FDA recently granted it the status of ‘breakthrough therapy’, meaning that scientists have more access to the drug and support for their research. How, then, can we be so sure of MDMA’s efficacy if the research is so new? It turns out that research into MDMA’s therapeutic effects dates back to the ’70s.

MDMA, a History

MDMA was first synthesized in 1912 by Dr. Anton Köllisch, working for the German pharmaceutical company Merck. Back then, it was used as a compound to create the antihemorrhagic hydrastinine. The literature goes out of its way to point out that the belief MDMA was used to create appetite suppressants is wrong, suggesting that this is a widespread misconception. Nevertheless, it wasn’t until the 1950’s that MDMA was put through toxicological studies to determine its own merit. In 1953 and 1954, the CIA experimented on humans with compounds similar to MDMA, seeking a truth serum of sorts, and had to stop when one study participant died. Subsequently, the CIA conducted animal studies with MDMA and produced the first data on MDMA’s psychoactive properties.

This inauspicious beginning perhaps foreshadowed the dual nature of the drug. On one hand, MDMA creates a sensation of interconnectedness and trust, aiding with therapy such as that suggested for PTSD; on the other, it’s this same trusting effect that can be used to coerce subjects.

By the 1970s, enough was known about MDMA that a group of therapists had become interested in integrating its use into healing practices. 1976 marked the start of the ‘Boston Group’ and its influence in the world of psychedelic therapy. The group “consisted of a chemist, a few persons interested in spiritual development and psychotherapy, and others associated with the MIT Artificial Intelligence Lab” and distributed MDMA periodically throughout the Boston area.

At the time, MDMA — or “Adam” as some therapists had taken to calling it due to the perceived innocent state of people under its influence – was legal in the United States, even though similar compounds were already prohibited. It was only a matter of time before the FDA would stop the legal production of MDMA. From about 1976 to 1985, when ‘Adam’ was finally banned, notable figures such as chemist Alexander T. Shulgin and psychologist Leo Zeff were responsible for thousands of patients receiving MDMA-assisted therapy. Zeff had switched over from MDA after realizing MDA’s high toxicity and possibly lethal side effects. MDMA, by contrast, carries a much lower risk, and cases of overdosing on Ecstasy — a name often conflated with MDMA — are usually due to the product being mixed, or ‘cut’, with a variety of other drugs such as amphetamines or cocaine.

The 70s were Wild West days for pharmacology in some senses, as the FDA had not approved psychedelic treatments, yet networks of underground practitioners provided psychedelic sessions for their patients. During this time, protocols were developed that continue to be influential for researchers hoping to employ psychedelic-assisted therapeutic techniques. For example, the potential for abuse of patients under the influence was recognized, especially after two infamous cases of sexual abuse during sessions, and so psychedelic therapy now includes two therapists, one male and one female, in every session to ensure inappropriate behavior is kept to a minimum.

It wasn’t until the 1990s that the FDA officially approved the first human trial of MDMA’s therapeutic potential. By that time there were already scores of medical and anecdotal documents to draw from. Since then, it’s been a slow but steady struggle to establish the positive aspects of MDMA and restore the reputation of what is often seen as merely a party drug. Much of the information for this history lesson comes from scientific articles whose sole aim is to correct misconceptions about the drug. Even then, part of the difficulty of creating medicine for the mind is integrating personal experience into data sets that prove a certain drug or another is effective for treatment. The challenge is to create protocols with repeatable results and doses with provable efficacy so that industry, doctors, and the government can work together to unlock the full potential of MDMA.

How MDMA Works

 “Caution:” begins PsychedSubstance’s YouTube Video What MDMA Feels Like. “We do not promote the use of legal, or illegal psychoactive substances. This video has been created strictly for harm reduction purposes.” Adam, simply ‘Adam’ like ‘Cher’ or ‘Madonna’ (although I’m sure he doesn’t intend it that way), has taken many psychoactive substances, and in this video he opens up about the terrible effects of MDMA abuse. Although it is generally agreed that MDMA is not addictive in a chemical sense, the euphoria it brings about makes it psychologically tempting to return to often. And once the body habituates to the drug, which happens easily, many people, including Adam, report feeling profoundly suicidal without it. This is because the drug taxes the body’s serotonin receptors, and it may take months for the body to recover. Therefore, any implementation in a therapeutic setting will have to be sparing. At low doses and with enough time between uses the risk of adverse long-term effects becomes practically non-existent. The main concern becomes providing the proper ‘set’, or setting, for the participant to avoid a bad ‘trip’.

Adam has a disarming style of presentation and is a great resource for anyone wishing to understand what it feels like to use MDMA without having to do it. He outlines an order of events one is likely to experience when ‘rolling’ on MDMA, or ‘Molly’, its current street name (The name ‘Molly’ is used to distinguish a substance as pure MDMA crystals as opposed to ‘Ecstasy’ which has come to be expected to be ‘cut’ with other drugs, although there is no guarantee that street dealers will be honest when using said naming conventions).

It is common to experience initial anxiety before sensations begin to feel more pleasurable. Vision might become more vibrant, and a desire to talk begins to take over. There may be nausea or stomach upset. At a certain point, many users report an intense feeling of euphoria. Depending on dosage and sensitivity, a feeling of wholeness or “universal interconnectedness” may occur. Touching oneself or others can feel “over the top pleasurable,” and music sounds great. It sounds like a welcome reprieve for people living with PTSD. Yet, there are a minority of users who report feeling anxious throughout.

In terms of biology, the video MDMA (Ecstasy) | Mechanism of Action & Metabolism contains a simple to understand visual companion to explain the neurological processes that produce the ‘high’ MDMA is known for. In the simplest terms, the MDMA molecule resembles serotonin, dopamine, and norepinephrine in structure, fooling reuptake receptors to allow it into the cytoplasms containing the mood-altering chemicals. From there it disrupts the natural flow of chemicals from the cytoplasm to the synapse and back, meaning that the brain is flooded with serotonin, dopamine, and norepinephrine. This accounts for the wide spectrum of effects attributed to MDMA.

In the long term, psychedelics like MDMA seem to promote growth in the brain’s dendrites, branches that grow from a neuron to receive information. Psychedelics also affect the number of connections between neurons. This mechanism could account for the profound experiences reported while under the influence of psychedelics, leading to lifelong changes in perception.

The possibility for MDMA to turn gene expression ‘on’ or ‘off’ is also due to the molecule’s shape, this time binding to DNA and changing its behavior. With enough generations of cells reproducing the modified gene, changes could become permanent or passed on through generations. The type of insights a person experiences while on MDMA, then, becomes of crucial importance to long-term healing.

To help maximize positive outcomes, practitioners such as Ann Shulgin and Leo Zeff began creating strategies for their patients. While Zeff would create an atmosphere of isolation and introspection, Shulgin delved into discussion using work inspired by Carl Jung.

“One of the problems that most humans [sic] beings suffer from” she says, “is the suspicion that the core essence of who they are deep down is a monster… MDMA removes that fear… Once you get inside the demon, the first thing you experience is a lack of fear, and then you begin to recognize that this is also the survivor aspect of yourself. There’s a part that takes care of you. Then it begins to transform, and you recognize its quality of total selfishness—it’s going to take care of you and nobody else, right? —but it’s your ally. And then you begin to recognize its positive aspects.”

Modern methods include using cognitive behavioral therapy (CBT) in conjunction with MDMA. The commonality between all these approaches is addressing a major hurdle PTSD sufferers face when integrating traumatic experiences. Before a therapist can even begin to help a patient integrate, the patient must recall the traumatic event without experiencing uncontrollable trauma-related responses. The process of learning to control what feels like instinctual reactions to environmental triggers adds months or years to therapy and can discourage patients from continuing treatment. MDMA essentially bypasses this preliminary phase because the drug suppresses activity in the amygdala and hippocampus, parts of the brain responsible for the ‘fight or flight’ response. Without the worry of re-traumatizing the patient, therapists can help explore traumatic memories and create new pathways in the brain that decouple associations from the fear response. Psychedelics make the brain pliable singularly, allowing permanent changes to occur sometimes in a single session.

Although official documentation is relatively new, underground proponents of MDMA-assisted therapy lay the foundation for what could prove to be the leading form of therapy before the end of this decade. Once enough data is collected to validate anecdotal evidence, multiple pharmaceutical companies are set to fill the future market demand.

 Companies to Watch in Psychedelics

MDMA shows promise not only in treating PTSD, but various mood disorders as well. The work of various companies and non-profits such as the Multidisciplinary Association for Psychedelic Studies (MAPS) will form models of integrated healing. Here are some industry leaders exploring the full potential of MDMA.

Numinus Clinics are conducting clinical trials of MDMA for the treatment of PTSD. They also administer Ketamine for treatment-resistant depression and psilocybin-assisted therapy.

Xphyto Therapeutics Corporation has invested considerable resources towards developing industrial-size processes for the synthetization of psychedelics such as psilocybin and MDMA. They are also innovating drug delivery methods, such as oral and nasal applications. Their research will help ensure safe, dependable dosages.

Novamind, a company currently focused on Ketamine therapy distribution, is also researching the role of MDMA in treating eating disorders.

MindMed, a medical company, announced on April 5th, 2021 that it has published new data on personalized dosing of MDMA. Although MindMed doesn’t focus on PTSD, understanding what factors like weight and age do to MDMA users will be essential across the board. One of its projects involves combining MDMA and LSD to mitigate bad trips.

EHave is creating mental health informatics platforms that it is currently using as part of its Ketamine treatment program, but it hopes to extend its program once psychedelics hit the pharmaceutical market.

Mindset Pharma is developing therapies that use MDMA as part of its psychedelics program.

It can be intimidating trying to decide which psychedelics company to invest in. Companies with an MDMA program have the advantage of researching a compound that is gaining buzz in the realm of PTSD, and has a history of therapeutic use. This is merely a sampling of the companies interested in developing MDMA into a viable therapeutic drug. In the near future, don’t be surprised to see the number expand.