Behavioral and genetic analysis of the effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) in C. elegans.
bioRxiv : the preprint server for biology – May 23, 2025
Source: PubMed
Summary
Scientists discovered that a psychedelic compound strongly affects feeding behavior in microscopic worms, but through unexpected pathways. Using the simple organism C. elegans, researchers found that while the drug DOI didn't impact movement or reproduction, it significantly reduced feeding - surprisingly without involving serotonin receptors, the usual target of psychedelics. This reveals new possibilities for how these compounds work.
Abstract
Psychedelics show promise in treating depression, PTSD, and substance use disorder, prompting research into their mechanisms of action. Most studies use rodent models, but genetic tools can be challenging to apply. Invertebrate models, like C. elegans , offer a cost-effective alternative with short generation times and genetic tractability. This study examined the worm's response to the psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) by assessing four serotonergic behaviors. Effects of DOI exposure on locomotion speed, swimming frequency, and egg-laying were undetectable but DOI strongly inhibited feeding. Interestingly, this effect was independent of serotonin receptors, suggesting DOI may act through alternative pathways. These findings indicate C. elegans can serve as a useful model for studying psychedelic drug effects, potentially revealing novel mechanisms beyond the serotonergic system. Further research could help clarify these pathways, improving our understanding of the therapeutic potential of psychedelics and refining their efficacy in treating neuropsychiatric disorders.