Simple Analogs of the LSD D-Ring: A Consideration of Structure-Activity Relationships and Their Potential as Therapeutics.
ACS Chemical Neuroscience November 5, 2025 DOI: 10.1021/acschemneuro.5c00695 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Population | Rodents |
| Topics | LSD |
| Keywords | Animals Humans Hallucinogens Structure-activity relationship Therapeutics Psychedelic D-ring Structure−activity relationships sar Nonhallucinogenic |
| Citations | 1 |
| Key points | Argues that simple D-ring analogs of LSD are nonhallucinogenic, nontoxic in testing to date, and can block the behavior-disrupting effects of psychedelics in rodents, but that these mature data warrant reinvestigation with current tools; further testing of binding, plastogenic effects, and psychiatric utility is needed, and D-ring structural changes may enhance other LSD-related analogs in clinical trials. |
Abstract
Psychedelic drugs have begun to show therapeutic promise. However, there is a growing research effort focused on creating nonhallucinogenic analogs of these substances. The goal is to develop new treatments for an expanding list of psychiatric and neurodegenerative disorders, while eliminating the complications and costs of treatment engendered by the subjective psychedelic experience. Structure-activity relationships (SAR), particularly for LSD (d-lysergic acid diethylamide), have guided many of these efforts. This perspective examines the historical development and behavioral testing of several simple analogs of LSD's D-ring, which, while nonhallucinogenic and nontoxic within the context of their testing to date, can block the behavior-disrupting effects of psychedelics administered to rodents. However, these data are quite mature. D-ring analogs of LSD may have therapeutic potential but require further testing to examine binding, plastogenic effects, and potential utility in psychiatry and neuromedicine, and are ripe for reinvestigation with current tools, approaches, and concepts. Further, the SAR data strongly suggest that the incorporation of several changes to the structural elements of the D-ring may enhance the effects of other LSD-related analogs currently undergoing clinical trials.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 2
Cites 35
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and 30 more in the library