Appraisal of the validity of preclinical investigations to predict the efficacy of psychedelic drugs as fast-acting antidepressants.

Each incident of failure of a novel drug to translate from preclinical experiments into the clinic increases the pressure to justify the use of animals in these experiments and for the interpretation of findings to be valid and convincing. This is especially the case with research of psychedelics, because they have already been tested extensively in humans. One reason for failure to translate is that preclinical research findings and conclusions are rarely, if ever, confirmed independently. Another is an incautious interpretation of the validity of the animal models that are used, in respect of their relevance to the human disorder of interest and its treatment. This article discusses both these points in the context of preclinical investigations of psychedelics as fast-acting antidepressants, but the generic points are relevant to other human disorders as well.