Speaker Bio
Gabriël Jacobs (1977) was trained as a general adult psychiatrist and clinical pharmacologist at the Leiden University Medical Center (LUMC) and Centre for Human Drug Research (CHDR) in Leiden. He obtained his PhD on the clinical pharmacology/neuroendocrinology of the Hypothalamic-Pituitary-Adrenal axis (HPA) from Leiden University in 2010, after which he completed his clinical residency in psychiatry. From 2013 to 2016, he held a position as consultant psychiatrist at the department of general hospital psychiatry at the VU Medical Center in Amsterdam. He currently holds the position of Research Director Psychiatry at CHDR and Consultant Psychiatrist at the Department of Psychiatry of the LUMC. In addition, he supervises an internship in Clinical Psychopharmacology for residents in psychiatry at CHDR, which is recognised by the Dutch national Training Programme.
ICPR 2024 Abstract
First-in-Human Studies with Novel Psychedelic Compounds: Pharmacological Characterization Based on the Question-Based Drug Development (QBDD) Approach
The clinical development of novel psychedelic compounds can benefit from the so-called Question-Based Drug Development (QBDD) approach 1. To illustrate this, we present two studies conducted with the prototypical NMDA receptor antagonist ketamine and the classical 5-HT2A agonist dimethyltryptamine (DMT). Central nervous system (CNS) biomarkers that had previously been demonstrated to be sensitive to CNS penetrating compounds, were implemented in these studies to objectify these compounds’ pharmacodynamic (PD) profiles. These included measures for arousal and vigilance, alertness, attention, psychomotor function, subjective psychomimetic effects, neuroendocrine hormones, and changes in quantitative electro-encephalography (qEEG) power. At the same time, the pharmacokinetics (PK) were extensively characterized in order to establish PK-PD relationships. The QBDD approach allowed for detailed characterization of the safety, PK and PD of ketamine and DMT in healthy volunteers. Also, PK characterization elucidated PK-PD relationships that might inform dose selection for future trials. Together, QBDD can be applied in studies with novel psychedelic compounds to characterize their safety, PK and PD profiles, which in turn is expected to facilitate benchmarking to previously characterized compounds with similar or more selective mechanisms-of-action, and ultimately, inform rational dose selection in subsequent clinical development phases.
1 Cohen AF, Burggraaf J, van Gerven JMA, Moerland M, Groeneveld GJ. The Use of Biomarkers in Human Pharmacology (Phase I) Studies. Annual Review of Pharmacology and Toxicology. 2015 Jan 6;55(1):55–74. ”