How is Ketamine Different Than MDMA?

MDMA has become a beacon of psychedelic medicine advancement recently, and for good reason. Largely due to the work of MAPS (Multidisciplinary Association of Psychedelic Science) pushing MDMA for post-traumatic stress disorder (PTSD) through clinical review trials, and it is currently moving through Phase 3 clinical trials with a “Breakthrough Therapy” designation from the FDA.

The early results and potential have many potential psychedelic therapy candidates asking what the difference is. Why might someone choose MDMA over ketamine for psychedelic medicine work? What are the subjective and biological differences between the experiences and the compounds?

This resource will explore the differences between Ketamine and MDMA when used in the context of psychedelic therapy and as psychedelic medicines.

Exploring MDMA

MDMA is known as “Molly” or “Ecstasy” in recreational circles, and “3,4-Methyl​enedioxy​methamphetamine” in the scientific and clinical communities. It was first synthesized in 1912 by Merck laboratories, and subsequently popularized and released by Sasha Shulgin, a legendary chemist, biologist, and early pioneer of MDMA and other psychedelic compounds. Before becoming a Schedule 1 substance, it was used therapeutically under the supervision of clinicians/therapists from the mid 1970’s-80’s.

MDMA is often included in the list of psychedelic therapy medicines, though it may be better described as an empathogen or entactogen. This means focused on emotions, feelings of empathy, and/or connection with self, others, and the world. This is because the subjective experience of MDMA differs in kind from the traditional definition of a psychedelic medicine, and does not include the hallmarks of a psychedelic/mystical experience.

MDMA comes with its own list of contraindications and considerations, as any psychedelic medicine does. There is ongoing research and study into the neurotoxicity of MDMA, though when working within clinical and therapeutic contexts, this does not seem to be a major concern. MDMA carries a body load, or physical sensations, and has implications for heart health, blood pressure, and resting heart rate when screening candidates.

The experience someone has with MDMA varies based on the set, setting, intentions, and dosing protocol that is used. MDMA has gained a reputation in the recreational party/rave scene, but as new science is showing, it also has profound potential when used to help individuals heal, turn inward, and cultivate new levels of self-love and respect.

As it stands at the time of this writing, MDMA is currently an illicit, illegal, and scheduled substance in most of the world. However, clinical trials are underway to prove the efficacy and potential of MDMA when combined with psychotherapy, particularly directed towards the treatment of PTSD.

MDMA Neurobiology

MDMA works primarily in the brain by acting on the serotonin system, activating these pathways and preventing the reuptake of serotonin. By increasing the levels of serotonin (and also norepinephrine) in the system, this leads to the subjective and hallmark experiences of MDMA: increase in energy, increase in empathy, mood elevation, and altered sensory experiences such as more vivid colours and sensitivity to physical touch.

It does have an impact on the 5HT2A receptor, which is classically used to define psychedelic compounds neurobiologically, however it is not the central activating force, and this is why the classification of MDMA as a classical psychedelic is commonly debated.

Some of the effects of MDMA include:

• Euphoria: general well-being and positive affect
• Increased empathy towards self and others
• Relaxation and reduced anxiety
• Enhanced sensation, perception, & sexuality
• Mildly altered sense of time
• Dampened fear/safety response
  

Some of the potential side-effects of MDMA include:

• Dehydration
• Hyperthermia
• Increased wakefulness (potentially insomnia)
• Increased heart rate/blood pressure
• Loss of appetite
• Erectile dysfunction
• Mild (and rare) auditory or visual hallucinations
  

Where MDMA becomes such a strong psychotherapeutic agent is its ability to help quiet down the fear and safety mechanisms of the brain, such as lowered activity in the amygdala, the fear centre of the brain.

When used in combination with traditional psychotherapy, this effect allows clients to revisit past experiences, memories, or traumas that may normally be blocked from accessing or feeling. They’re then able to and revisit these experiences with more compassion, more openness, and more love for themselves and others involved. This revisiting of pain and trauma allows individual narratives to be rewritten, for clients to come to a more holistic framing of the event, and determine the healing steps to take forward from there.

From the neurobiological perspective, the differences between MDMA and Ketamine become more apparent and obvious. They are separate compounds with different mechanisms of action, and with different impacts on neurochemistry, ultimately leading to separate and distinct phenomenological experiences.

MDMA Phenomenology

MDMA as an empathogen and entactogen is often considered “heart-opening.” It commonly leads to embodied experiences centered around compassion and empathy for self, others, and the world.

The experience does not contain most of the hallmarks of a classic psychedelic experience, such as distortions of time and space, out of body experiences, novel insights or connections.

The experience follows a predictable time arc, with first sensations noticeable around 30-45 minutes after ingestion, and in the psychotherapeutic containers a “booster dose” is offered after an hour or so. The experience tends to last about 3.5 hours, with a calm “comedown” window of a few hours after that. Individuals tend to be present and available throughout the experience, complimented by the amphetamine component present within MDMA.

This combination of presence, energy, openness, and compassion is what makes the MDMA experience conducive to challenging psychotherapeutic work. The client and clinician are able to explore territory that may previously have been inaccessible due to fear, regressions, or an emotional inability to revisit, discuss, and explore those experiences or memories.

Many clients remain present and coherent throughout the experience, which when paired with a trained psychotherapist, create a calm, open space to discuss the individual's life, and revisit and reframe historical experiences that may still be active in the individual at the moment.

The experiences often involve feelings of love, connection, and empathy, and sensory sensitivity to lights, sounds, smells, and touch.

Differences Between Ketamine & MDMA

There are a few core distinctions to make between MDMA and Ketamine in the context of psychedelic therapy. This is not a debate as to which medicine is better, but they are both uniquely suited to address specific conditions within appropriate treatment plans.

Some of the key distinctions include:

MDMA is a non-traditional psychedelic

Of course, the first is that MDMA does not include a classic psychedelic experience. There is value in the psychedelic experience, though it is not the only way healing occurs, oftentimes, the open-loving state produced by MDMA is sufficient to explore challenging or haunting memories/experiences and make considerable progress.

They act on different neurobiological mechanisms

MDMA, Ketamine, and other psychedelic medicines all have different neurobiological mechanisms of action. Ketamine largely addresses the Glutamate system, whereas MDMA works primarily on the Serotonin system.

MDMA is particularly effective for trauma/PTSD

As mentioned, MDMA appears to be uniquely well-equipped to help individuals, alongside a practicing therapist, to work through complex and deep-rooted PTSD. This is the medical and clinical application currently moving through Phase 3 clinical trials.

MDMA compliments traditional therapeutic modalities

Due to the length and accessibility of the experience, MDMA works well within traditional psychotherapeutic contexts. Unlike experiences with psilocybin or LSD, which can run anywhere from 6-12 hours in length, MDMA is more approachable, and indeed works better when combined with traditional talk therapy modalities. It can fit within standard working hours, and allows deeper progress to be made for both the individual and the clinician.

The discussion of distinctions between psychedelic medicines may seem trite or nuanced, but will increase in importance over time. Ketamine and MDMA are both powerful and healing medicines, and they come with their own lists of strengths, contraindications, and considerations.

Noticing these distinctions helps clinicians and clients maximize the healing process, and allows individuals to re-center themselves around their families, friends, and work that they love.

The Future of MDMA-Assisted Psychotherapy

As mentioned, MAPS is currently spearheading clinical trials of MDMA for PTSD and is currently moving into Phase 3 trials —the final trial step before approval from the FDA to make MDMA therapy a legitimate and legal clinical treatment modality.

Given the ongoing support of the FDA (due to the “Breakthrough Therapy” designation), and the promising results from the previous Phase 1/2/3 trials, the landscape looks promising to have MDMA-assisted psychotherapy available for eligible clients by 2023.

This would be the second psychedelic medicine (after Ketamine) to be legally and clinically available to serve those in need. This in itself is exciting, and would mark a significant step forward in making psychedelic therapy available and accessible to those who need it.

An important point that Rick Doblin, founder of MAPS, points to is the fundamental importance of psychotherapy as the necessary and central part of this healing process. MDMA is used as a catalyst to open up in the individual, imbue a sense of trust and safety in themselves and with the therapist. But it is the psychotherapy that is the demonstrated driver of enduring positive change over time. An important clarification is that MDMA-assisted psychotherapy is going through clinical trials right now, rather than simply allowing individual dosing sessions of MDMA without additional support.

This is another beautiful potential for the future of psychedelic medicine and MDMA as a medicine overall: continued improvements, refinements, and new studies around the best dosing protocols, the right set & setting, and appropriate levels of ongoing integration and preparation support throughout the experience. Progress through research benefits the psychedelic medicine space, and the future of MDMA-assisted psychotherapy looks bright. MDMA is becoming a recognized medicine, along with bringing new information to the entire psychedelic therapy space at large.

Conclusion

As the field of psychedelic therapy grows, and the legality of psychedelic medicines increases, the discussion around which medicines are best suited to address which conditions and clients will become more pronounced and more nuanced.

What’s important is that individuals receive the right treatment at the right time. More of these medicines are moving through regulatory requirements, and doing what they do best —helping people heal.

MDMA is still a substance classified as illegal, but there is promise and hope that MDMA for PTSD will become a clinically-available treatment in the coming years, bringing hope and healing to those directly affected and in need of this medicine.

If you are considering psychedelic medicine and would like to get started, ketamine treatment is available, and you can determine your eligibility for treatment by taking our client intake survey.