In brief
- A team at the University of California, Davis, dismantled the structure of LSD piece by piece to determine which fragments trigger the psychedelic experience and which support its therapeutic utility.
- They synthesized nine simplified versions of the ergoline molecular scaffold; two, dubbed UCD0094 and UCD0076, showed reduced 5-HT2A and 5-HT2B activity with preclinical interest; human cardiac safety was not established.
- In behavioral tests with mice, UCD0076 functioned as an antipsychotic. The release was dated September 7; PNAS/PMC index electronic publication on September 8 and remain preclinical research, far from any human application.
On September 7, a team from the Institute for Psychedelics and Neurotherapeutics at the University of California, Davis, shared results on LSD deconstruction from a PNAS paper indexed as electronically published on September 8. They designed nine variants of its molecular core, ergoline, to separate the parts of the molecule that trigger the hallucinogenic effect from those that support therapeutic effects. Two of these variants retained useful activity with lower hallucinogenic potential and lower 5-HT2B activation than LSD, without thereby establishing lower human cardiac harm.
Which piece triggers the trip
LSD acts on several serotonin receptors simultaneously. The 5-HT2A receptor is behind the hallucinogenic effect; the 5-HT2B receptor is associated with cardiac toxicity—the same mechanism that forced the withdrawal of other drugs like fenfluramine from the market—and the 5-HT2C receptor is linked to antipsychotic properties. The team, led by David E. Olson, removed rings and substituents from the four-ring LSD framework to see what survived in each version. They found that hallucinogenic activity follows the fragments of the molecule with a phenethylamine-type structure more closely than those of the tryptamine type, providing a concrete lead for those looking to design LSD-derived drugs without the trip. Those wishing to place this finding within the broader map of psychedelic substances will find the general context there.
Two candidates and an unexpected twist
Of the nine synthesized versions, two stood out: UCD0094 and UCD0076 showed lower hallucinogenic potential and lower 5-HT2B receptor activation, without losing the activity that makes them interesting as a pharmacological starting point. Furthermore, UCD0076 showed a preference for the 5-HT2C receptor and, in behavioral tests with mice, behaved as an antipsychotic—a striking twist for a molecule descended from a substance historically associated with the trip rather than calming it. The authors note that compounds activating 5-HT2C are also being explored for epilepsy and substance use disorders, although this study establishes antipsychotic-like activity in animal assays rather than clinical efficacy.
What this implies
This is textbook preclinical research: the results are in mice and laboratory assays, not people, and separating the trip from the therapeutic utility of a molecule requires years of subsequent work in synthesis, pharmacology, and safety before even considering a first clinical trial. Olson himself presents these compounds as starting points for medicinal chemistry, not as finished drugs. Neither of the two exists outside the laboratory, nor have they been tested in humans. For those who want to handle the actual LSD circulating today with more information and less risk, the harm reduction and responsible use page of Psiconáutica remains the starting point.
Source
- David E. Olson et al. Stripped-down LSD reveals structural features linked to hallucinogenic and therapeutic effects (Deconstruction of Lysergic Acid Diethylamide, PNAS). Phys.org, September 7, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
