Why Methylone Is Chosen Over MDMA for Psychedelic Therapy

In 2017, after reading Michael Pollan's "How to Change Your Mind," a book that made the New York Times' 10 Best Books of the Year list, the speaker had a significant shift in perspective regarding psychedelics. Despite never having considered or tried them before, the book convinced him that these substances could be medically beneficial, citing academic research on their potential to treat PTSD, depression, and anxiety.

At the time, he was on the board of Yale and became aware of the foundational work being done there, including that of John Crystal on ketamine and Ben Kendi. He became a significant donor to the Yale Center for Psychedelic Research, believing that psychedelics would become very effective and important, a realization he felt most people had yet to grasp.

Transition to a For-Profit Model

By 2021, in discussions with Ben Kendi, a professor and "superstar" in the field, the speaker concluded that the next phase for psychedelic research and development needed to be a for-profit one. This decision was driven by the substantial cost of getting a single compound through the FDA approval process, estimated at $200-$250 million. Such an amount, he argued, could not be raised through non-profit donations alone.

This led to the idea of starting a company. Working with Ben Kendi and Blake Mandel from his team, they developed the concept for a new venture focused on methylone. Blake Mandel eventually spun out of the speaker's existing company, Alcorp, to become the CEO of this new psychedelic company.

The Choice of Methylone

The decision to focus on methylone was strategic, aiming for a compound that was not widely known but showed promising preliminary results. The speaker highlighted several advantages of methylone over MDMA, despite acknowledging MDMA's therapeutic and recreational benefits.

Key advantages of methylone include:

• Less Toxicity: Methylone is less toxic and depletes serotonin less than MDMA, allowing for more frequent use. While MDMA is often recommended for use no more than four times a year to maintain its "magic" and avoid resistance, methylone could potentially be taken once a week in trials.
• Reduced "Downer" Effect: Users of methylone tend to experience less of the "downer" or negative after-effects sometimes associated with MDMA.
• Shorter Duration: Methylone has a shorter duration of action, making it more compatible with existing healthcare models and easier to integrate into therapeutic settings.

The company initiated the process of conducting double-blind studies for methylone, and the initial results were described as "incredible."

Indications and Patent

The company holds a patent for methylone's use in treating PTSD, depression, and anxiety, granting them exclusive rights for 20 years in these categories. However, due to the high cost of FDA approval for each indication ($200 million per indication), they had to prioritize. They began with one indication, likely PTSD, given the challenging fundraising environment for psychedelics two years prior, often referred to as the "desert period."

Learning from Ecosystem Challenges

The speaker acknowledged the difficulties in the psychedelic space, including stigma and fundraising challenges. He also noted common mistakes made by early ventures:

• Scalability of Long-Duration Treatments: The difficulty of scaling treatments that last four to six hours, requiring extra staff and significantly increasing costs, making them potentially "out of reach."
• Bundling Psychotherapy: The issue of combining psychotherapy with psychedelic treatments. The FDA advisory committee struggled to evaluate or standardize psychotherapy, leading to difficulties in approval.

The speaker emphasized the importance of learning from these "unforced errors," likening their approach to the saying, "The early bird gets the worm, but the second mouse gets the cheese." This implies that observing and adapting to the challenges faced by earlier entrants allowed them to refine their strategy and avoid similar pitfalls.