Eleusis, a clinical stage life science company established to develop the therapeutic potential of psychedelics, today announced the publication of its sponsored preclinical research in the American Chemical Society’s journal Chemical Neuroscience, which suggests that psychedelics may have more persistent antidepressant therapeutic efficacy than ketamine. The study also indicates that the antidepressant effect of psychedelics are both biological and context-dependent, and the subjective existential experience or “mystical experience” often associated with psychedelics may be correlated with, but not cause, the persisting antidepressant effect.
The publication, titled "Psychedelics, but not ketamine, produce persistent antidepressant-like effects in a rodent experimental system for the study of depression" is the first direct preclinical comparison of the antidepressant efficacy of psychedelics and ketamine. The research reveals that both psilocybin and lysergic acid diethylamide (LSD) significantly reduce depressive-like behaviors five weeks after a single administration, while only the lowest dose of ketamine evaluated (5.0 mg/kg) was efficacious in decreasing depressive-like behaviors, and that the associated antidepressant-like effects of a single treatment with ketamine were transient compared to those observed in the psilocybin and LSD-treated rats and lasted less than two weeks.
The environment research animals were exposed to in the days immediately following treatment with psilocybin shaped the nature of the antidepressant-like and anti-anxiety outcomes, suggesting that contextual experiences following drug treatment were important factors in determining overall responses. The research suggests this may be due to enhanced learning of new coping behaviors as a result of psilocybin or LSD administration, an effect not observed in animals treated only with ketamine, or saline.
“Our research is the first direct comparison of the degree and duration of antidepressant-like effects of psychedelics and ketamine in animals, and the first to demonstrate that what the animal experiences the first week after drug administration influences its long-term behavioral outcome. We believe these results further support the promising research and development of psychedelics as therapeutic medicines.” said Meghan Hibicke Ph.D., the study’s lead author and Postdoctoral Researcher at LSU Health Sciences Center, Pharmacology and Experimental Therapeutics.
“Prior to our study, the scientific premise of whether or not a profound subjective existential experience is necessary for psilocybin to have antidepressant effects had not been evaluated either clinically, or preclinically,” said Charles Nichols Ph.D., the director of the study and Professor of Pharmacology at Louisiana State University. “Based on our findings, we believe that the robust antidepressant effects of psychedelics are intrinsically linked to a biological response, which may be correlated with, but not dependent on, the profound subjective experiences associated with psychedelics.”
“These intriguing findings suggest that continued research will yield new understandings of the basic mechanisms giving rise to the robust and enduring effects of psychedelics,” said Shlomi Raz, Chairman and founder of Eleusis. "These study results, and other ongoing research directed by Eleusis, further confirm the vast therapeutic potential of psychedelics, and are serving to accelerate our company’s ongoing efforts to transform psychedelics into medicines.”