Professor David Nutt | DMT Stroke Consultant , Algernon Pharmaceuticals

April 30, 2021
Spotlight
David Nutt is a psychiatrist and the Edmond J. Safra Professor of Neuropsychopharmacology in Imperial College London. He has been president of the European Brain Council, the BAP, BNA, and ECNP. He is currently Founding Chair of the charity DrugScience.org.uk. David has published 35 books and over 1000 papers, including in Nature, Cell Lancet and New England Journal of Medicine. These define his many landmark contributions to psychopharmacology including GABA and noradrenaline receptor function in anxiety disorders, serotonin function in depression, endorphin and dopamine function in addiction and the neuroscience and clinical utility of psychedelics. Professor David Nutt is now involved with Algernon Pharmaceuticals as a consultant on their DMT Stroke Program.

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How is Algernon Pharmaceuticals different from other pharmaceutical companies and what made you decide to get involved with Algernon?

Algernon is focused on finding new uses for older known drugs, compared to a typical drug research company that is advancing new drug compounds, which I found to be quite interesting. They seem to be agile and can move quickly on projects. As it relates to working with them on their DMT stroke program, I think it’s a very good idea and wish I had thought of it myself.

What is your role at Algernon Pharmaceuticals and what do you hope to contribute to their drug development?

I have been retained as a consultant for their DMT stroke research program and I hope I can provide them with direction and advice on their clinical research program as it advances, based on my deep  expertise on the topic of psychedelic compounds and my direct experience as a scientist, researcher and clinician.

Can you talk about what you are investigating with DMT?

What we are going to be investigating with DMT is to see if it can help reduce the damage that occurs in the brains of patients who have suffered a stroke. DMT reduced the infarct volume in the brain (area of dead cells) and improved the recovery of motor function when given to rats who had the blood supply to one side of their brain tied off.  We are hoping to see the same or similar effects in humans who have suffered a stroke and have been given DMT.  We also intend to see if DMT can help a patient improve the outcome of their physical rehabilitation therapy,  which can begin as early as 24 hours after a stroke has occurred.

What early validation have you seen for DMT to be a potential therapeutic treatment for people who have suffered a stroke?

While there has been in-vitro research by Olsen showing how DMT can cause an increase in neurogenesis and neuroplasticity when exposed to cortical neurons, perhaps the most compelling is Nardai’s pre-clinical work last year from Hungary. Nardai conducted the rat stroke model that I referenced earlier, where the rats who had been made to suffer a stroke, had been given DMT and had a much better outcome than that rats who were in the untreated group.

What is AP-I88 and how do you hope to use it?

AP-188 is a new form of DMT that has been developed by Algernon. There are a lot of companies trying to compete in the psychedelic space and this is hard to do when most of the compounds, like DMT, are all naturally occurring. There are some very smart bio and organic chemists out there who can look at a molecule and make some slight changes to it that make it much easier to patent. This is the case with AP-188.

What is the importance of neuroplasticity in the treatment of stroke patients?

Neuroplasticity will occur when multiple brain cells regenerate, re-establish, and rearrange neural connections in response to the damage caused by a stroke. The brain in essence is doing a work around to help itself recover. Increasing this effect should result in better outcomes for patients.

For stroke patients, especially ischemic strokes, which occur when a blood clot blocks blood flow to the brain, it’s important to receive blood thinners or medication within a very short time window. Will this DMT program face a similar time constraint? If not, can you explain why?

That’s a good question…. Algernon is working to determine a number of things in their pre-clinical work and Phase 1 study, including confirming the correct dosage to achieve a sub-psychedelic effect of DMT, the best time to treat the stroke patient post insult and the duration of treatment. There are many unknowns and that is where the heavy lifting of early research comes in.

For these treatments, you’ll be working with a sub-hallucinogenic microdose of DMT. Can you talk about why it’s important, especially for stroke patients, to minimize the hallucinogenic effects of DMT?

I think it’s pretty intuitive that if you have suffered a stroke, sending someone on a psychedelic journey could be destabilizing and cause a negative effect with the patient. We already know how strokes can cause significant neurological damage including an impairment of one’s cognitive abilities. We don’t want to add to that burden.  A number of drugs that were being researched for stroke that ended up causing hallucinations were abandoned for this reason including NMDA receptor antagonists.

What other clinical trials have been done on DMT and how will those benefit Algernon’s research?

There have been a number of Phase 1 trials completed on DMT from the 1980’s led by Dr. Rick Strassman to recently, Small Pharma’s Phase 1 completed at Hammersmith. There is always much to learn from each study, however one of the key take aways is that DMT can be infused into a patient safely and without any serious toxic side effects. Over 34% of new drugs fail in their Phase 1 study due to safety reasons and so fortunately Algernon need not worry about DMT. This means it should be clear sailing into Algernon’s Phase 2 studies.

How will your experience and background help Algernon advance their clinical trials?

Proper clinical trial design can be exceedingly complex as well as understanding the data once a study is completed. I hope that my extensive experience in the field will help guide Algernon in the early planning stages and as the studies progress to help ensure the best possible outcome in hopes of discovering new treatments for stroke.
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