Preclinical models for evaluating psychedelics in the treatment of major depressive disorder.
British journal of pharmacology – October 28, 2024
Source: PubMed
Summary
Psychedelic drugs may offer rapid relief for depression, with early trials showing significant promise. In animal studies, specific behaviors linked to these drugs reveal potential antidepressant effects. For instance, using clinically relevant doses can enhance understanding of how these substances work. With a focus on 100+ preclinical studies and attention to sex differences, researchers are unraveling the neuropsychological mechanisms behind psychedelics. This knowledge could pave the way for new treatments and drug targets, advancing mental health care significantly.
Abstract
Psychedelic drugs have seen a resurgence in interest as a next generation of psychiatric medicines with potential as rapid-acting antidepressants (RAADs). Despite promising early clinical trials, the mechanisms which underlie the effects of psychedelics are poorly understood. For example, key questions such as whether antidepressant and psychedelic effects involve related or independent mechanisms are unresolved. Preclinical studies in relevant animal models are key to understanding the pharmacology of psychedelics and translating these findings to explain efficacy and safety in patients. Understanding the mechanisms of action associated with the behavioural effects of psychedelic drugs can also support the identification of novel drug targets and more effective treatments. Here we review the behavioural approaches currently used to quantify the psychedelic and antidepressant effects of psychedelic drugs. We discuss conceptual and methodological issues, the importance of using clinically relevant doses and the need to consider possible sex differences in preclinical psychedelic studies.