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Key points
- An FDA advisory panel votes against MDMA psychedelic science, but its approval remains a possibility.
- A new study of ketamine therapy for PTSD, awaiting peer review, shows high efficacy and safety for PTSD.
- There’s much to learn about psychedelic safety from how we currently deliver ketamine.
As a Drug Enforcement Administration (DEA)-licensed medical doctor who has administered ketamine nearly 10,000 times to people with mental health conditions, my team and I are frequently asked how ketamine compares to methylenedioxy-methylamphetamine (MDMA) and other psychedelic therapies for post-traumatic stress disorder (PTSD). In recent years, there’s been major momentum and enthusiasm for emerging therapies like MDMA for PTSD. But a meeting of Food and Drug Administration (FDA) advisors recently created new uncertainty for the field, as the non-regulatory, independent advisors cast a decisive “no” vote on the safety and efficacy of MDMA therapy,
These results came as a surprise to many, given the strong data on MDMA published across multiple studies in the top science journal Nature. Meanwhile, Australia has recently authorized MDMA and psilocybin as medicine—and in Switzerland, MDMA and psilocybin have been prescribable by registered physicians for over 10 years. Clearly, there is reason to believe that MDMA and other psychedelics show strong promise for individuals seeking new options.
Many of the FDA advisors’ issues had more to do with how we design clinical trials for these complicated substances than with the therapy itself; it is difficult to “blind” a study when the agent under investigation produces such distinctive effects. Ultimately, the FDA may still approve MDMA as soon as August. The situation is not unprecedented; in one-third of instances when FDA advisors vote no, the agent is nevertheless approved for use.
Given the recent uncertainty about the fate of MDMA, it’s a question with a significant impact; in today’s mental health crisis, nearly one in ten Americans will suffer from PTSD, and existing treatment options are ineffective for approximately 50% of people. While there is not one solution that's right for everyone, we must educate the public in anticipation of new approvals while also paying careful attention to the options already accessible today.
As co-founder and chief medical officer of Nushama Psychedelic Wellness, a center that is now the largest provider of in-person IV ketamine therapy in New York City, I am happy to share what my team and I have learned about ketamine therapy for PTSD.
Effectiveness: Ketamine vs. MDMA
Recently, we documented strong results using IV ketamine for PTSD, so we were inspired to publish our data, currently in the preprint stage while it’s undergoing peer review. Here’s what we learned:
- The largest real-world outcomes study of IV ketamine for treatment-resistant PTSD showed large and lasting symptom reductions.
- Of 117 participants who received IV ketamine for PTSD, 88 (75.21%) symptom measures showed clinically meaningful improvement, and 72 (61.54%) suggested remission of symptoms.
- These results are on par with MDMA and emerging therapies for PTSD, and they strongly exceed outcomes seen with standard selective serotonin reuptake inhibitors (SSRIs) and talk therapy.
- Ketamine therapy offers unique flexibility and safety for individuals taking other psychiatric medications.
- Long-term mental health benefits do not come from psychedelics alone; they are most effective in combination with a psychedelic therapy framework.
In this study, individuals received ketamine-assisted therapy in a highly supportive environment, with a psychedelic therapy approach—sensory immersion with music and eyeshades (to facilitate inward experience), intention setting, preparation and integration therapy, a supportive care team, and moderately high doses.
Lead study author Henry MacConnel, MSW, notes, “These results mark a turning point, as they show how a real-world, psychedelic therapy approach to IV ketamine may substantially improve PTSD outcomes compared to past research.”
Additionally, MacConnel shared, “These data allowed us to show for the first time that IV ketamine’s PTSD effects were significantly greater in participants who received ongoing psychotherapy.”
Ketamine Today
IV ketamine is an anesthetic agent developed in the late 1960s with a 50-year track record of safety in medically supervised settings. Ketamine administration doesn’t usually affect a person’s respiratory drive, cardiac function, or gag reflexes. Over the years, the medicine was found to be effective for mood disorders, especially treatment-resistant mood disorders. Ketamine is most commonly used in the ER on children as anesthesia and is given in much higher doses than in psychedelic therapy.
Ketamine is a dissociative anesthetic, although not in the typical sense of the word; it's more of an ego-dissociative. When used in sub-anesthetic doses, IV ketamine allows us to move away from our usual sense of self to see and appreciate our experiences from a different perspective.
Unlike MDMA, ketamine does not interfere with psychiatric medications like SSRIs, which a vast majority of individuals seeking treatment take daily. SSRIs can pose significant complications when people are attempting to taper off long-term use.
While ketamine is known to increase blood pressure, we screen for people with hypertension, uncontrolled high blood pressure, and other potential contraindications with a complete medical and psychiatric intake. In comparison, MDMA is a stimulant drug that places greater stress on the heart; in unmonitored recreational settings, such as hot dance clubs, overheating can, in rare cases, be lethal. Further, as FDA advisors recently noted, many patients with cardiac conditions may still be unsuitable candidates for MDMA therapy, even in monitored clinic settings, due to these stimulant effects. In contrast, the more benign cardiac effects of ketamine could be more safely tolerated.
MDMA Tomorrow?
There’s much to learn about psychedelic safety from how we deliver ketamine in a safe and medically supervised psychedelic framework. Ketamine has been extensively researched and utilized in various medical settings, offering valuable insights into how we can safely provide it as therapy. Here are key lessons that can inform how MDMA is administered:
1. Structured Clinical Environment. Ketamine therapy is conducted in a controlled clinical environment with medical supervision. This ensures that people are monitored throughout, from medical consults to post-treatment follow-up. The presence of trained medical professionals helps manage adverse reactions promptly and effectively, ensuring safety at all times. This structured approach can be applied to other psychedelics, including MDMA, to provide a high level of security and care.
2. Medical and Psychiatric Intake. Before starting ketamine therapy, participants undergo a full medical and psychiatric evaluation to determine their eligibility for treatment. This includes screening for contraindications such as uncontrolled hypertension or certain cardiac conditions. Implementing rigorous screening protocols for other psychedelics can help identify individuals who may be at higher risk and ensure that only those who are deemed safe receive treatment.
3. Preparation and Integration Therapy. Ketamine therapy is most effective when combined with therapeutic preparation and integration. The supportive environment at our clinic includes preparation sessions, intention setting, and integration therapy, which help people process and make sense of their experiences. This holistic approach enhances therapeutic outcomes, ensuring people glean key takeaways to implement into their daily lives, and can complement MDMA and other psychedelic treatments.
4. Monitoring and Managing Physiological Effects. While ketamine can increase blood pressure, this effect is well-understood and can be managed through careful monitoring and pre-treatment screening. By understanding and anticipating the physiological effects of ketamine, clinicians can ensure safety throughout the treatment process. This knowledge is transferrable to other psychedelics, where close monitoring of vital signs and preparedness to manage potential side effects can similarly enhance safety.
5. Continuous Data Collection and Research. At Nushama, ongoing data collection and research are vital in refining treatment protocols and improving outcomes. Similar to how we collected data regarding IV ketamine for PTSD, by documenting and analyzing real-world outcomes, clinicians can identify best practices to inform the broader psychedelic therapy field. Continual data collection for MDMA and other psychedelics will help build a robust understanding of their potential.
Costs and Barriers
As with any therapeutic process, an investment of time and money is often unavoidable. Ketamine is FDA-approved for chronic pain and anesthesia but prescribed off-label as a mental health treatment. Given ketamine’s status as a generic drug, insurance does not commonly cover its highly established, data-driven use as an off-label medicine. However, momentum continues building for broader insurance coverage. Moreover, ketamine’s cousin, esketamine, distributed as the nasal spray Spravato, is a valuable option for individuals to consider when insurance coverage is top of mind. We recently started offering Spravato in person at Nushama to increase access to the therapeutic benefits of ketamine.
Meanwhile, outside reviewers have begun to estimate the treatment cost of MDMA. In the event of approval, insurance coverage will remain highly limited at first and could exceed $25,000 for a full round of treatment. We’re encouraged that individuals can access ketamine at a fraction of that cost, with many financing and insurance options to drive affordability.
In Conclusion
Like a psychedelic journey itself, we’re on a path into the unknown: It remains to be seen whether MDMA will become a legal psychedelic therapy option in the United States outside of clinical trials. Meanwhile, after 50 years of research and 10,000-plus sessions in our center alone, we know a great deal about the promise, safety, and efficacy of ketamine for PTSD and many other mental health conditions.
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