The lysergamide 1P-AL-LAD is characterized and tested in vitro and in mice. In pooled human liver microsomes, 1P-AL-LAD converts to AL-LAD as the most abundant metabolite, supporting the idea that it acts as a prodrug. Fourteen metabolites are detected, including hydroxylation and deacylation products. In mice, 1P-AL-LAD produces a dose-dependent increase in head twitch response, a behavioral proxy for human hallucinogenic effects, with an inverted U-shaped dose-response curve. Its median effective dose is 491 nmol/kg, almost three times less potent than AL-LAD (174.9 nmol/kg). The prodrug mechanism likely explains its activity despite N1-substitution disrupting 5-HT2A receptor activation.
6-APB, a recreational drug similar to MDMA, produces effects at very low doses (0.01 and 0.1 mg/kg) in mice, while impairing short-term fear memory and long-term context memory at 5 mg/kg. It also causes modest locomotor sensitization and may produce addiction. Reduced shock reactivity appears due to ataxia rather than analgesia. The behavioral profile broadly resembles MDMA, but amnesic effects emerge at higher doses than MDMA, and there is a larger gap between potential therapeutic doses and doses causing cognitive deficits. These findings suggest 6-APB may not be a low-risk therapeutic alternative to MDMA.
Serotonergic psychedelics such as LSD, psilocybin, and MDMA significantly alter neural activation in several regions of the cerebral cortex and basal ganglia. Some effects are common across these drugs, while others are unique to each substance. This meta-analysis combined functional MRI studies of both clinical and healthy participants, using multilevel kernel density analysis with ensemble thresholding. The findings clarify the functional neuroanatomy associated with these drugs and may guide future research into their therapeutic and adverse effects, particularly for emerging psychiatric treatments.