The development of translational tasks for preclinical psychedelic research in psychiatry

Psychiatric disorders represent a particularly challenging area of medicine to study using non-human animals. They arise from a complex interaction between genetic and environmental factors and are diagnosed using clinical interviews and diagnostic criteria based largely on self-reported symptoms and with significant heterogeneity seen within patient populations. Anxiety and major depressive disorder are the most diagnosed psychiatric disorders, with prescriptions of antidepressants exceeding 80 million in the UK in 2024. Despite more than 70 years of research, we do not understand how antidepressants achieve their effects on mood. With a resurgence in interest in developing new treatments based on clinical advances in the psychedelic field, there is a pressing need for translational methods to study the underlying mechanisms and provide reliable predictions of clinical effects. Human studies are limited in terms of the resolution of current imaging methods and the depth of mechanistic interrogation which can be achieved. Studies involving non-human animals offer an important avenue to understand how psychedelics alter behaviour and the underlying mechanisms mediating these effects, as well as playing a critical role in the development of new drugs. However, the value of these studies in terms of delivering outcomes for patients will only be achieved if the methods used have clinical relevance. In this perspective article, I consider whether 'behavioural biomarkers', and their translation to animal tasks, could achieve this much-need approach.