PsychExchange Podcast

Imagine this - you’re in the lab and you’ve just discovered a novel psychedelic compound. It shows promising results in treating depressive symptoms with minimal side effects  in your mouse model of depression. You may be on the brink of a groundbreaking therapeutic discovery and aspire to commercialize your finding into a biotech startup. But before diving forward, there’s a catch - the world of intellectual property and patents. In today’s episode, we delve into the complex yet crucial world of psychedelic intellectual property. What exactly patents, why are they essential in safeguarding your innovations? How do they compare with data exclusivity in protecting your technology?  There’s no better person to guide us through this maze than our guest expert, Gretchen Temeles, Ph.D, J.D. Dr. Temeles is an experienced intellectual property attorney with extensive experience in counseling clients in the psychedelics and cannabis space in formulating comprehensive global IP strategies. She has also advised universities, startups, mid market companies, and multinational corporations, and is also a thought leader, serving on the Scientific Advisory Board of Palo Santo VC, a psychedelic therapeutics investment fund.  Dr. Temeles combines her legal expertise with her scientific background as a former group leader in a biotech company focused on small molecule drug discovery in therapeutic areas that included neurological disorders, inflammation, cancer and infectious disease. This unique blend of skills makes her an ideal guide to understanding the importance of robust intellectual property protection, especially in the burgeoning field of psychedelic therapeutics.

The term “neuroplasticity” has become inextricably linked to the concept of how psychedelics may give rise to their therapeutic effects. But what really is neuroplasticity, and how can scientists measure it in the lab? How does pre-clinical research on rodent models permit a deeper understanding into the underlying mechanisms of how psychedelic treatments work? How does the primary psychotropic compound in psilocybin, commonly referred to as “Magic Mushrooms,” affect neuroplasticity, and may this be linked to adaptive behaviors? Tune in as Dr. Alex Kwan, Associate Professor at Cornell University, discusses how his laboratory has leveraged key techniques in cellular, circuit, and behavioral neuroscience to help uncover the neuroplastic mechanisms of psilocybin in preclinical models of psychiatric disease. __________________ Dr. Kwan’s bio: “I am an associate professor in the Meinig School of Biomedical Engineering at Cornell University. I received a Ph.D. in Applied Physics from Cornell University, where I worked on nonlinear optical microscopy in the laboratory of Watt Webb. For postdoctoral studies, I was a Croucher Fellow studying cortical microcircuits with Yang Dan at the University of California, Berkeley. Before joining the Cornell faculty in 2022, I was an associate professor in the Department of Psychiatry at Yale School of Medicine. The Kwan lab applies systems neuroscience and neuroengineering approaches to the study of mental health. We develop optical imaging techniques to visualize neural dynamics in awake mice. We design quantitative decision-making paradigms to characterize behavior. We often complement the imaging and behavioral experiments with other molecular, electrophysiological, optogenetic, and computational methods. Current effort in the lab is directed towards two topics: (1) Drug action in the brain: Psychiatric drugs exert powerful effects in humans characterized by altered perception, cognition, and mood. The lab studies the action of psychoactive drugs, including ketamine and serotonergic psychedelics such as psilocybin, on the function and connectivity of neurons in the frontal cortex. (2) Decision-making: Animals use past choice and reward history to guide their current decisions. We are interested in how neural circuits may implement reinforcement learning, and whether reward learning dysfunctions may be a useful metric to quantify neuropsychiatric conditions.” - engineering.cornell.edu. Further reading: Recent publications from the Kwan lab: A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics. Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Ketamine disinhibits dendrites and enhances calcium signals in prefrontal dendritic spines. Shared and distinct brain regions targeted for immediate early gene expression by ketamine and psilocybin. Upcoming publications: The neural basis of psychedelic action. Kwan AC, Olson DE, Preller KH, and Roth BL. Psychedelics and neural plasticity: therapeutic implications. Grieco SF, Castrén E, Knudsen GM, Kwan AC, Olson DE, Zuo Y, Holmes TC, and Xu X.

The opioid epidemic both arises from and perpetuates a global crisis in pain treatment: How can we effectively treat pain while reducing the impact of addiction on individuals and society? Is ketamine the answer? In this episode, Dr. Jeffrey Becker, the CSO of Bexson Biomedical discusses their novel insulin pump-inspired delivery system for ketamine, ketamine’s application to chronic pain, and what inspired him to explore the clinical applications of psychedelics. “Dr. Becker has over 20 years of research and clinical experience in NMDA-receptor pharmacology and clinical use. He was one of the first MDs in U.S. administering and documenting ketamine for depression in the clinic, and is a world recognized speaker and expert in the clinical use of ketamine. His expertise led to development of an effective nutraceutical product addressing NMDA-receptor abnormalities. He received his B.S. from UC Berkeley and M.D from UCLA. He maintains a clinical practice focused in Functional Psychiatry and novel treatment approaches to mental health challenges.” - bexsonbiomedical.com Further reading: Bexson Biomedical’s patent application: https://patents.justia.com/patent/10973780 Ketamine in the pain clinic: Peri-operative ketamine reduces post-operative opioid requirements. A review of impact of ketamine on pain perception and one’s relationship towards pain. A meta-analysis of clinical studies investigating the efficacy of ketamine for chronic pain.

Dr. Cameron, postdoctoral scholar at Stanford, discusses her seminal work characterizing DMT and the non-hallucinogenic psychoplastogen tabernanthalog during her PhD in the David Olson Lab at UC Davis. To understand how psychedelics work, we use models of the human brain to systematically isolate effects on cells, circuits, and behaviors. These models include animal models - “in vivo,” commonly mice or rats, when behavior is particularly important - and cell cultures of lab-grown neurons - “in vitro,” when the molecular and cellular signaling mechanisms are particularly important. But what’s the point of giving animals and dishes of disembodied neurons psychedelics? After all, it’s unlikely they could “trip” like humans “trip.” How does this translate to the clinic? Ultimately, what even is the point of preclinical research? In this episode, Stanford postdoctoral fellow Dr. Lindsay Cameron discusses her pioneering work as a doctoral student in the laboratory of Dr. David Olson at UC Davis, where she authored multiple game-changing papers. In two papers, Dr. Cameron characterizes the effects of the short-lasting, but extremely potent psychedelic DMT on behavior and neurophysiology in the rodent model. In 2021, she authored a paper characterizing an analog of the non-classical psychedelic ibogaine developed in the Olson laboratory called tabernanthalog (TBG). This paper is a case-in-point argument for the importance of preclinical research: based on what we know about the effects of the hallucinogenic, cardiotoxic, and anti-addictive drug ibogaine, Dr. Cameron progressively tests their novel compound in increasingly complex models of the brain - from plated cells, to zebrafish, to rodents - to demonstrate the potentially non-hallucinogenic, non-cardiotoxic, yet still anti-addictive properties of TBG. Because of the tests Dr. Cameron and her colleagues ran, we now have reason to think TBG could be a much safer and less costly alternative to plant/fungus derived psychedelics, which nonetheless preserves their neuroplastic and clinically useful properties. TBG is one of the proprietary compounds of Delix Therapeutics. Dr. Cameron is currently a postdoctoral fellow in the laboratories of Dr. Robert Malenka and Dr. Karl Deisseroth at Stanford University. A selection of Dr. Cameron’s publications: First author: Cameron & Olson 2022 “The evolution of the psychedelic revolution.” Neuropsychopharmacology. Cameron LP, et al. 2021 “A Non-Hallucinogenic Psychedelic Analog with Therapeutic Potential.” Nature. Cameron LP, et al. 2019 “Chronic, Intermittent Microdoses of the Psychedelic N,N-Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents.” ACS Chemical Neuroscience. Cameron LP, et al. 2018 “Effects of N, N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression.” ACS Chemical Neuroscience. Cameron & Olson, 2018 “Dark Classics in Chemical Neuroscience: N, N-Dimethyltryptamine (DMT).” ACS Chemical Neuroscience. Other: Unger et al. 2020 “Directed Evolution of a Selective and Sensitive Serotonin Sensor via Machine Learning.” Cell. Ly et al. 2018 “Psychedelics Promote Structural and Functional Neural Plasticity.” Cell Reports.

In this episode, your hosts Adrienne and Sophie share what drew them to neuroscience and how they developed a shared passion for psychedelic research. Sophie summarizes the current state of psychedelic research in academia, while Adrienne explains the role of drug discovery & development in bringing these discoveries to the public. Tune in if you're interesting in exploring a general background of psychedelic science and biotech before jumping into our interviews, or if you simply want to meet your hosts!