Advancing Psychedelic Compounds: From Preclinical Discovery to Translational Insight

Recent advances in psychedelic research are uncovering the potential of both traditional 5-HT2A-preferring hallucinogens (e.g., LSD, psilocybin) and non-hallucinogenic 5-HT2A receptor agonist compounds (e.g., 2-Br-LSD; BOL-148). These compounds may provide therapeutic benefits for conditions poorly managed by current treatments, such as treatment-resistant depression, obsessive-compulsive disorder (OCD) and substance use disorders. Although only suggested by preclinical studies, the promise of non-hallucinogenic agonists offers an opportunity for more accessible, scalable mental health interventions that remain effective while minimizing the intense subjective effects that can hinder clinical use.

2-Br-LSD (BOL-148) provides a valuable case study as a reference non-hallucinogenic 5-HT2A agonist. Structurally similar to LSD, 2-Br-LSD interacts with serotonin receptors (notably 5-HT2A) but does not elicit hallucinogenic effects. This significant distinction allows researchers to distinguish therapeutic mechanisms, such as receptor activation and neuroplasticity, from perceptual disturbances. These insights are essential for creating next-generation psychedelics that maintain clinical benefits while enhancing tolerability and safety.

Two useful preclinical tools in this effort are: drug discrimination (DD) and chronic social defeat (CSD). DD is a behavioral pharmacology technique historically used to evaluate the subjective effects of psychoactive compounds in animals, while CSD is a paradigm based on psychosocial stress. In the current psychedelic renaissance, both techniques are being leveraged to answer two pressing questions in drug discovery: (1) For reference psychedelics such as LSD, psilocybin, DMT and 5-MeO DMT, how do plasma concentrations needed to induce perceptual effects translate between rats and humans? and (2) Can these behavioural assays distinguish between classical hallucinogens and non-psychedelic 5-HT2A agonists?

This webinar will examine the role of DD and CSD techniques in mapping the pharmacological profiles of emerging psychedelics, claimed non-psychedelics and established psychedelics. Attendees will gain insights into how these findings may inform the development of safe, effective treatments for mental health disorders. The session will be particularly relevant to researchers and clinicians in psychopharmacology, neuroscience and drug development interested in the forefront of psychedelic science.

Register now to explore the latest in psychedelic development and psychiatry, including preclinical insights and novel therapeutic strategies.

Speakers

Guy Higgins, PhD, Global CSO, Transpharmation Ltd., Adjunct Professor, Department of Pharmacology & Toxicology, University of Toronto

Dr. Higgins has significant experience in CNS drug discovery and early clinical development, exemplified by contributions to over 15 NCEs entering the IND enabling phase, and three reaching the market. He is the listed inventor of more than 20 patents and has authored over 160 original research papers and review articles published in peer-reviewed journals spanning a 35-year period. Since 2008, he has focused on using this experience in the domain of contract research, supporting clients in their drug R&D efforts.

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Ewa Sokołowska, Director & Head, Transpharmation Poland

Ewa is the author of several publications and poster abstracts. Initially, she worked at Transpharmation Ireland Ltd, where she successfully established multiple preclinical studies and led a team of young scientists. For the last two years, she has led a team of scientists at the Transpharmation Poland site. Her research interests include all aspects of novel animal models with possible high clinical significance.

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