12-Methoxy-LSD


12-Methoxy-LSD is a drug of the ergoline and lysergamide families and a derivative of lysergic acid diethylamide. In terms of chemical structure, 12-methoxy-LSD is to LSD as 5-MeO-DMT is to dimethyltryptamine, with 12-methoxy-LSD notably containing 5-MeO-DMT within its conformationally constrained structure. Both 12-methoxy-LSD and its analogue 12-hydroxy-LSD have been described as non-hallucinogenic in humans. However, in other more recent reports, 12-hydroxy-LSD produced psychedelic-like effects in rodents and was said to have similar activity as LSD in humans.

Pharmacology

It has been reported that 12-methoxy-LSD does not produce hallucinogenic effects in humans. However, it is nonetheless pharmacologically active in animal studies. The drug's effects in rabbits include antiserotonergic activity and hyperthermia. In addition, like LSD, it is highly potent in terms of lethality, with a median lethal dose of 0.1mg/kg in rabbits. 12-Methoxy-LSD also produces LSD-like electroencephalogram changes in rabbits.
Presumably 12-methoxy-LSD acts as an agonist of serotonin and dopamine receptors, as with LSD and other related lysergamides, but its pharmacology has not been studied with modern techniques.

Chemistry

Synthesis

The chemical synthesis of 12-substituted lysergamides is described as being very difficult.

Analogues

An analogue of 12-methoxy-LSD is 12-hydroxy-LSD, which would be structurally akin to bufotenin. As with 12-methoxy-LSD, it has been reported that 12-hydroxy-LSD is inactive as a psychedelic in humans. Contrary to this report however, Michael Valentine Smith claimed in his 1981 book Psychedelic Chemistry that 12-hydroxy-LSD has "about the same activity as LSD". In addition, 12-hydroxy-LSD has been found to substitute for LSD in rodent drug discrimination tests with about 20% of its potency.

History

12-Methoxy-LSD was first described in the scientific literature by 1967. Subsequently, it was further described in the 1970s and 1980s.