The First Study To Compare the Effects of LSD and Psilocybin Behind the Scenes

The First Study To Compare the Effects of LSD and Psilocybin Behind the Scenes ...

For the first time, a study revealed the effects of varied dosages ofpsilocybin and LSD. These two popular psychedelics have increased interest in clinical research. The study examined placebo, LSD (100 and 200 mg) and psilocybin (15 and 30 mg). MindMed, an established practitioner in the psychedelics medicine industry, has conducted a double-blinded, randomized and placebo-controlled group.

Barrow became the CEO of a clinical stage private pharmaceutical company before joining the Usona Institute in 2020. He says his vision for MindMed was to develop a holistic health care practice that can efficiently manage multiple assets. It''s an ambitious objective. In this interview, he discusses how this approach has been implemented in 2022.

How are the doses in psychedelic drugs determined and measured? Ruairi J Mackenzie (RM)

Dosing is one of the key features you need to fully characterize during your crucial phase III studies. Depending on whether or not you do, there are certain abilities that may influence dosing on an individual basis, and you''re likely to arrive at a dosage that you believe is going to support the patient''s clinical outcomes.

When we think about dosing with psychedelics, there has been, however, decades of research to quite understanding the pharmacokinetics and dynamics, and we have really well-known how the interactions work out.

If you want to sell a drug at an affordable rate, you can end up with a fixed dose program, unless there''s a particular concern, often more of a concern for safety. Generally, psychedelics are labeled for an efficacy or pharmacodynamic reason, but they''re generally labeled because of safety. At this point, we feel that we are confident in the safety that we intend to pursue a fixed dose program.

LSD has been launched in a phase IIb dose optimization experiment. That''s really to explore which of those fixed doses reliably provides you the activity that you''re looking to generate both acutely, but also more important, in terms of clinical outcomes over the course of several weeks.

In a recent study, you compared LSD and psilocybin doses. What were the most important findings?

RB: The key finding is that LSD is more powerful than psilocybin (which we previously knew) but that it does not appear to cause the same acute psychoactivity and perceptual effects as psilocybin. What we aren''t certain of is whether acute activity directly influences the clinical response. Whether acute and perceptual effects are directly linked to these molecules, however, this study provides a solid evidence base to enable us to read across the assets.

As we look at psilocybin data, we gain confidence that we can learn from those findings and that they would be applicable to LSD, for example. This gives us an enormous additional opportunity to learn from research outside of our own programs. It continues to de-risk our approach and provide us more opportunities for expansion of our label and where we might go with marketing one day if these therapies are approved.

RM: Are you surprised by these results?

RB: Given the thousands of patients who have been administering LSD and psilocybin, and anecdotally, you can certainly look at the evidence and say, these are going to behave similarly. However, it''s important to definitively establish these things. At the end of the day, it''s not particularly surprising that there''s quite a similar activity.

What you need to know about LSD''s differences between LSD and psilocybin, and whether or not it is more reliably inducing a certain response at a given dose? In terms of clinical activity, there''s still a lot to be discovered about that translation.

In a population with a diagnosis, this was not done. It''s important to understand if there''s a similar response in the clinic, or how they differ. Among the many observations we have from our staff who have worked with LSD for a long time, is that it may be even better at managing the clinical outcomes. Now, we must prove that.

RM: Recent discussion on blinding in clinical trials has erupted. Participants were able to guess if they were taking a medication or a placebo 96% of time. What are the options they may adopt to mitigate these problems?

RB: It''s a fascinating topic, and I''ve had a lot of interest from both researchers and the FDA in this matter. While the FDA and other researchers are discussing this topic, we''ve found that while niacin has been offered up many times, and that clinical trials have used diphenhydramine. It''s likely to be difficult to completely blind LSD or psilocybin in a two-arm study, however, it''s going to be very difficult.

It''s also important to not forget that this is not a unique problem to psychedelics. Very often, there is a clear perceptual effect that will make it difficult to blind.

In the esketamine database, you should consider ketamine, which is a dissociative agent. If you look at the adverse event tables for esketamine versus placebo in the esketamine database, you can see that the esketamine group is one of the two molecules that made up the racemic mixture of ketamine and was approved for treatment resistant depression in 2019, the dissociation rate in the esketamine arm was significantly higher than in the placebo group.

RM: After two years in psychedelics research, how do you feel that MindMed has shifted towards your goals of increasing high-throughput research in the past?

RB: The organization has grown significantly over the last year. We''ve got about ten employees, and now we''re at around six times that. pharma, like us, who understand how to handle big organizations and how to handle complex tasks in a scalable manner, and handle multiple tasks at the same time. We have been very successful in this process, particularly since recently. We are still working on a number of new initiatives and projects, as well as in the future.

As we look out for the next year or two years, there will be a variety of data sets that will be very helpful to us and the world''s large public, revealing where LSD is possible and where we believe other molecules might fit into the pipeline.

In the second half of last year, we added a program called the MDMA R-enantiomer for treatment of autism spectrum disorder. We''re keeping an eye on what we''ve already seen, but we continue to see a huge opportunity that extends beyond a single asset and a single indication, and we continue to make advancements across all our programs to achieve this goal.

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