Lykos Therapeutics, formerly MAPS Public Benefit Corporation, has announced it has received FDA acceptance and priority review for a New Drug Application (NDA) concerning its MDMA-assisted therapy for PTSD.

The FDA has accepted Lykos’s NDA for MDMA capsules used in combination with psychological intervention. This intervention includes psychotherapy and other supportive services provided by a qualified healthcare provider for individuals with PTSD. 

Lykos has stated that the FDA has granted the application priority review and has assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 11, 2024. Current statistics show that 89% of applications that meet their PDUFA deadline are approved. If this application is approved, it would make this the first MDMA-assisted therapy and psychedelic-assisted therapy.

In a press statement, Amy Emerson, chief executive officer of Lykos Therapeutics, commented: “Securing priority review for our investigational MDMA-assisted therapy is a significant accomplishment and underscores the urgent unmet need for new innovation in the treatment of PTSD.

“We remain focused on working with the FDA through the review process and preparing for a controlled launch with an emphasis on quality should this potential treatment be approved.”

The NDA submission was supported by results from several studies on the therapy, including two Phase 3 studies that looked at the efficacy and safety of the therapy. Both of these studies met their primary endpoints, which were a change in PTSD symptom severity and an improvement in functional impairment associated with PTSD. 

While no serious adverse events were reported in the MDMA group in either study, Lykos highlights that the safety and efficacy of MDMA-assisted therapy have not been established for the treatment of PTSD.

The news has been welcomed across the pond by European campaign groups advocating for access to psychedelic-assisted therapy. 

In a press statement, campaign group PAREA commented: “Innovation in mental health has stagnated for decades. In the past three years, Europe has approved only one new psychiatric treatment, compared to 68 in oncology. 

“While the U.S. is on the brink of approving the first psychedelic-assisted therapy, Europe significantly lags behind. This is primarily because the current incentives and rewards for companies to conduct large-scale pivotal trials on psychedelics are insufficient in Europe, highlighting the need for enhanced support and incentives to advance novel mental health treatments.”

While the US makes strides in advancing psychedelic healthcare, Europe is now beginning to take note of this scientific development, with the European Medicines Agency (EMA) set to hold a multi-stakeholder workshop on medical psychedelics in April 2024.

The workshop aims to establish regulatory guidelines for the development and therapeutic use of psychedelic substances in Europe.

The continent also made a recent historic advancement in the field of psychedelic research. In January 2024, the European Union announced €6.5 million in funding for research into psychedelic therapy as part of its Horizon Europe programme. 

The funding has been awarded to a consortium of 19 partners from nine different European countries for a clinical trial – the PsyPal trial – which will study psilocybin-assisted psychotherapy for psychological and existential distress in people who are diagnosed with either chronic obstructive pulmonary disorder (COPD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) or atypical Parkinson’s disease (APD). 

Doctors have raised a warning against so-called “trip killers” that are used to end challenging psychedelic experiences on compounds such as LSD or psilocybin.

The doctors have published the warning in a letter in the Emergency Medicine Journal. In the letter, an analysis of relevant Reddit threads is provided that show drugs such as benzodiazepines and antipsychotics recommended to help end these challenging psychedelic experiences. However, the doctors emphasise that these recommendations rarely include information about potential side effects.

A total of 128 Reddit threads created were discovered that were created between 2015 and 2023, yielding a total of 709 posts. With 440 recommendations, amounting to nearly half – 46% – of all the ‘trip-killers’ mentioned in posts, were various benzodiazepines, followed by several different antipsychotics at 171%.

The team found that one in 10 recommendations were for antidepressants, while one in 20 were for alcohol. Opioids, antihistamines, herbal remedies, such as camomile and valerian, and prescribed sleeping pills, attracted 3% each, with cannabis and cannabidiol at 2%.

Trip-killers were mostly discussed in reference to countering the effects of LSD (235 recommendations), magic mushrooms (143), and MDMA (21). Only 58 posts mentioned potentially harmful side effects.

The authors write: “The popularity of benzodiazepines raises concerns. Benzodiazepines are addictive and have been repeatedly implicated in overdose deaths. 

“The doses described on Reddit risk over-sedation, hypotension [low blood pressure], and respiratory depression [stopping breathing or shallow breathing].”

Doses of one of the recommended antipsychotics, quetiapine, were also high the authors note, with only a few posts differentiating between fast and slower release formulations.

“Information on trip-killers isn’t available through drug advice services, despite the probable risks they pose,” highlight the authors.

Dr Peter Sjöstedt-Hughes, Lecturer at Exeter University, has proposed incorporating metaphysical philosophy into psychedelic therapy to help improve therapeutic outcomes.

Sjöstedt-Hughes suggests that psychedelic therapy may gain more advantage by extending its scope into metaphysics, helping patients better integrate and understand psychedelic-induced metaphysical experiences.

Such improved outcomes may be seen if patients undergoing this therapy “are provided with an optional, additional, and intelligible schema and discussion of metaphysical options at the integrative phase of the therapy.” 

In the paper, Sjöstedt-Hughes puts forward this schema as the “Metaphysics Matrix” and an accompanying “Metaphysics Matrix Questionnaire (MMQ)” which can be utilised by therapists and researchers as a tool for the quantitative measurement of a psychedelic experience.

The paper ‘On the need for metaphysics in psychedelic therapy and research’ has been published in Frontiers in Psychology.

What is metaphysics?

While mysticism deals with understanding the universe through direct experience, such as revelation, metaphysics is a branch of philosophy that deals with understanding the fundamental nature of reality through logic/argument.

Sjöstedt-Hughes writes that “metaphysics is not mysticism” but there is overlap: “[…] metaphysics is broader and its positions can be logically deliberated — as such metaphysics can encompass mystical experiences induced by psychedelic intake yet metaphysics can also ground those experiences in a manner that can be more intelligible, comprehensive, viable, and acceptable to participants than that which the framework of mysticism alone can offer.”  

The Metaphysics Matrix

A number of clinical trials investigating psychedelic-assisted psychotherapy for the treatment of mental health conditions, such as anxiety and depression, report that participants who undergo a “mystical experience” during a psychedelic session often have higher levels of sustained therapeutic outcomes.

In clinical trials, mystical experiences are measured by different scales including the Mystical Experience Questionnaire (MEQ), the Hood Mysticism Scale (HMS), the Hallucinogen Rating Scale (HRS), the Five Dimensions Altered State of Consciousness Questionnaires (5D-ASC) and Eleven Dimensions Altered State of Consciousness Questionnaires (11D-ASC).

Sjöstedt-Hughes writes: “Data derived in this manner is obviously limited and abstract not only because psychedelic experience need not be “mystical,” but also because the definition of “mystical” could be expanded to include other criteria […] 

“With regard to psychedelic-assisted psychotherapy […] speaking about mystical experience per se will not be sufficient to provide a meaningful explanation of the significance of such experience to a person, for the simple reason that mystical experience is the phenomenon to be explained — mystical experience is the explanandum rather than the explanation. 

“It is metaphysics that is the means of explanation, the explanans of the mystical explanandum.”

The Metaphysics Matrix has been designed to provide a “menu” of metaphysical options that may help people to “frame, make sense of, and give significance to, their experiences”, and would be another tool in the belt of therapists to better understand these experiences.

Image provided by Dr Peter Sjöstedt-Hughes.

Such experiences could be understood through metaphysical systems such as Neutral Monism, Pantheism, Panpsychism, Animism, Substance Dualism, and Idealism, says Sjöstedt-Hughes. 

Some examples provided include the common experience of the Universe being God – which can be understood in the context of Pantheism – or of all matter having a basic form of sentience – such as plants having a basic drive or process – which can be understood in the context of Panpsychism. 

Image provided by Dr Peter Sjöstedt-Hughes.

Additionally, enabling people who have had these experiences to understand them within these frameworks may make them less likely to dismiss the experiences as delusional, says Sjöstedt-Hughes.

“ […] Relatedly, that the worldview hitherto adopted by the participant is but one metaphysical position amongst others,” he writes. 

Sjöstedt-Hughes commented: “This is a conjecture that hasn’t been tested but can be tested – offering a patient an additional and optional discussion in the integrative phase of psychedelic-assisted psychotherapy. 

“Giving them this Metaphysics Menu for integration may extend the long-term benefits of psychedelic therapy and beyond because there’s a number of studies that seem to show that certain peak psychedelic experiences have the longest and most beneficial health outputs results.

“If in the integrative phase [of therapy] one looks at that experience and starts to frame it intelligibly, then the conjecture is that the participant will not in a few weeks after that, think it must have been a delusion – they will say that we don’t know what reality is. 

“Therefore, we can’t dismiss something as a delusion necessarily. By doing that it might extend the significance of that experience for the person.

“When we use Mysticism Scales, by definition, mystery can’t explain itself. Metaphysics, however, incorporates those experiences and offers an explanation to what they mean. For example, the relation between oneself and the universe.”

Sjöstedt-Hughes points out that in practice, one of the immediate issues is the practical issue of implementation of Metaphysics Integration, suggesting this could be supported through resources such as a handbook or practitioner training.

He further concludes the integration would need to be “further bridged by the therapist to the participant’s life, concerns, values, aims, and outlook.”

The Metaphysics Schema is already being utilised in studies taking place at Ohio State University, US, and Exeter University, UK.