2-Oxo-LSD

2-Oxo-LSD, also known as 2-oxy-LSD or 2-keto-LSD, or more fully as 2-oxo-2,3-dihydro-LSD, is a lysergamide and metabolite of the psychedelic drug lysergic acid diethylamide. It is a metabolite of LSD in both humans and various animal species, although there are important differences in LSD metabolism and relative proportions of metabolites between species.

Metabolism

2-Oxo-LSD is formed directly from LSD in the body and is also possibly an intermediate in the generation of LSD's major metabolite 2-oxo-3-hydroxy-LSD, which is present in urine at concentrations 4 to 40times those of LSD in humans. However, O-H-LSD may also form from other metabolites, such as 3-hydroxy-LSD. The specific enzymes responsible for the generation of individual LSD metabolites like 2-oxo-LSD are largely unknown. However, several cytochrome P450 enzymes were investigated and implicated in the formation of O-H-LSD in 2019.

Pharmacology

2-Oxo-LSD showed absence of various pharmacological effects in animals. In contrast to LSD and certain other metabolites like 13-hydroxy-LSD, 2-oxo-LSD failed to produce LSD-like electroencephalogram changes in rabbits. 2-Oxo-LSD at a dose of 300μg orally produced no psychoactive effects in a human subject who had previously responded to 30μg LSD. It was concluded that 2-oxo-LSD shows no LSD-like activity in the central nervous system and hence is inactive. 2-Oxo-LSD's derivative O-H-LSD showed profound loss of activity at the serotonin 5-HT₂ receptors compared to LSD in vitro. 2-Oxo-LSD is said to readily enter the brain.

Chemistry

2-Oxo-LSD contains most of the clinically used dopamine D₂-like receptor agonist and antiparkinsonian agent ropinirole within its chemical structure.

History

2-Oxo-LSD was first described in the scientific literature by Julius Axelrod and colleagues in 1957.