In brief
- A team at the University of Arkansas for Medical Sciences (UAMS) tested four LSD analogs circulating in the gray market as legal alternatives: 1A-LSD, 1P-LSD, 1B-LSD, and 1cP-LSD.
- While all four showed lower affinity for serotonin receptors in test tubes, they fully substituted for LSD in animal behavioral tests.
- Blood tests revealed LSD levels similar to those found after taking LSD itself, indicating the body transforms these compounds into LSD.
- A fifth compound tested, LSZ, did not convert into LSD; it acts on the same receptors independently.
- The study, published in July 2026, was conducted on rats; caution is required when extrapolating these findings to humans.
A study published in July in the Journal of Pharmacology and Experimental Therapeutics provides a key piece of evidence regarding LSD analogs sold as legal substitutes for the classic substance: at least four of them—1A-LSD, 1P-LSD, 1B-LSD, and 1cP-LSD—are converted into pure LSD once inside the body. The findings, authored by Michael Berquist, William Fantegrossi, and their team at UAMS, help explain why substances that theoretically behave differently end up producing virtually identical effects.
Four molecules, one result
Analogs with a substitution on the indole nitrogen (the N1 position) of the LSD molecule began circulating years ago as a way to circumvent prohibition. By slightly modifying the structure, they avoid being listed as controlled substances while promising a similar experience. The researchers compared five of these compounds with original LSD on three fronts: their affinity for 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C serotonin receptors; their ability to substitute for LSD in a behavioral discrimination test with rats trained to recognize it; and their presence in the blood following injection.
In test tubes, the four N1-substituted analogs showed lower affinity or weaker efficacy than LSD at these receptors. Even so, in live animals, all four fully substituted for LSD: the rats recognized them as if they were the substance they had been trained to identify.
Blood reveals the reason
The answer emerged when analyzing the animals’ blood after injection: at the times relevant to the behavioral test, the levels of LSD detected were similar regardless of which analog had been administered. The body removes the chemical group added to the N1 nitrogen and releases LSD. In practice, these four analogs act as prodrugs for LSD.
The exception was LSZ, an analog with a substitution on the diethylamide portion rather than the indole nitrogen. This compound showed affinity for serotonin receptors similar to that of LSD itself, did not transform into LSD after injection, and produced its effects as an independent molecule.
Implications
This data has practical value for those who choose to use these analogs instead of LSD: if the body converts them into the same substance, the equivalent dose and duration of effect should be similar to those of LSD. However, the rate of this conversion may vary from person to person based on individual metabolism, which may help explain why some users describe experiences that are more intense or longer-lasting than expected with the same amount of product. Understanding these mechanisms, rather than just the brand name of what is being purchased, is part of harm reduction applied to a market that constantly evolves to dodge the law.
The research team notes the study’s limitations: it was conducted on rats using systemic injection rather than oral or sublingual administration, which is how these products are typically consumed in real-world settings. While metabolic conversion into LSD is well-established in the animal model, its exact magnitude in humans remains to be confirmed.
Source
- Berquist MD, Gannon BM, Honeywell KM, et al. Interoceptive effects of N1-substituted lysergamides in rats: role of agonist affinity at 5-hydroxytryptamine receptors and in vivo metabolism to lysergic acid diethylamide. Journal of Pharmacology and Experimental Therapeutics, July 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.
