In pursuit of psychedelics

Eleusis publishes preclinical research revealing long lasting antidepressant-like effects of psychedelics when compared to ketamine in animals

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LONDON & NEW YORK—Eleusis Ltd., a company established to develop the therapeutic potential of psychedelics, has announced the publication of its sponsored preclinical research in the American Chemical Society’s journal Chemical Neuroscience.
The research suggests that psychedelics may have more persistent antidepressant therapeutic efficacy than ketamine. The study also indicates that the antidepressant effect of psychedelics is both biological and context-dependent, and that the subjective existential experience often associated with psychedelics may be correlated with, but not cause, the persisting antidepressant effect.
“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,” said Meghan Hibicke Ph.D., a postdoctoral researcher at Louisiana State University (LSU) Health Sciences Center, Pharmacology and Experimental Therapeutics, and the study’s lead author. “We believe these results further support the promising research and development of psychedelics as therapeutic medicines.”
The publication, entitled “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. Only the lowest dose of ketamine evaluated (5.0 mg/kg) was efficacious in decreasing depressive-like behaviors. 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 that research animals were exposed to in the days immediately following treatment with psilocybin shaped the nature of the antidepressant-like and anti-anxiety outcomes. This suggests that contextual experiences following drug treatment were important factors in determining overall responses. The research notes that this may be due to enhanced learning of new coping behaviors as a result of psilocybin or LSD administration. This was an effect not observed in animals treated only with ketamine, or saline.
“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,” stated Charles Nichols Ph.D., the director of the study and professor of Pharmacology at LSU. “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. 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,” added Shlomi Raz, chairman and founder of Eleusis.
Back in December, Eleusis also announced results from their Phase 1 clinical trial of orally administered low doses of Lysergic Acid Diethylamide (LSD). The results, published in Psychopharmacology, include positive data on the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy older volunteers over a 3-week period.
“We are encouraged by the study results, which reveal that regular administration of low dose LSD to healthy older volunteers is well-tolerated, and that the frequency of adverse events associated with LSD is similar to placebo,” said Neiloufar Family, the study’s lead investigator and director of research at Eleusis.
Historically, LSD has been observed to exert clinically relevant therapeutic effects in patients afflicted by depression, anxiety and substance abuse. Prior research suggests that low dose LSD may have significant potential in treating Alzheimer’s disease. This trial was the first registered modern clinical trial on low doses of LSD.
The article, entitled “Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Low Dose Lysergic Acid Diethylamide (LSD) in Healthy Volunteers” provides data on a double-blind, placebo-controlled, randomized trial conducted in London, England. The trial enrolled 48 older volunteers (mean age 62.9 years old), who were randomly assigned to four dose groups: 5 µg, 10 µg and 20 µg of LSD, and placebo. Each received their assigned dose on six occasions (i.e. every 4 days) over three weeks and had a follow up visit at one month. Safety and tolerability measures included adverse event monitoring, blood pressure, heart rate, ECG measurements, clinical laboratory evaluations, balance, proprioception, cognition, subjective response measures, and psychiatric and physical health exams.
“Our research with serotonin 5-HT2A receptor agonists, such as LSD, suggest that they may represent a new strategy to treat diseases associated with chronic inflammation,” said Charles Nichols, co-author of the study and Professor of Pharmacology at LSU. “LSD’s unique polypharmacology may serve to enhance its capacity to simultaneously modulate multiple key pathological processes in the brain associated with Alzheimer’s disease, including neuroinflammation, that are implicated in its progression from mild cognitive impairment.”
Clinical review revealed no deviations from baseline or abnormalities on either safety or cognitive outcome measures. A minor and expected clinical difference between placebo and active treatment groups was the number of headaches reported. These were described as either mild or moderate in intensity. This suggests that at a sub-perceptual microdose level, LSD would not impede day to day activities.
“We are excited to share the results of this groundbreaking Phase 1 trial and believe it will serve as the foundation for the promising therapeutic development of LSD and other psychedelic drugs as subperceptual therapeutics,” added Raz in a press release. “We are committed to unlocking the therapeutic potential of psychedelics at subperceptual, non-psychoactive doses, to safely address the most urgent unmet needs in public health, and look forward to advancing both LSD into Phase 2 trials for Alzheimer’s disease, and our lead ophthalmology candidate, ELE-02, into trials for retinal disease.”
“The study provides reassuring safety data and opens the door for larger scale clinical trials to evaluate the potential therapeutic effects of LSD,” added Robin Carhart-Harris, head of the Centre for Psychedelic Research at Imperial College London.

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