Some psychedelic substances that carry the N-benzyl phenethylamine (NBOMe) structure can activate the µ opioid receptor (MOR), an off-target effect confirmed by two different assays. This activation was blocked by the opioid antagonist naloxone, indicating these NBOMes bind to the same opioid binding pocket as conventional opioids. Molecular docking showed plausible interactions of 25I-NBOMe with MOR similar to those of opioids. However, MOR activation occurred only at high concentrations, making relevant opioid toxicity in vivo unlikely at physiologically relevant levels. Small modifications to the NBOMe structure could yield more potent MOR agonists with dual MOR/5-HT2A activation potential.
The synthetic stimulant 2-Cl-4,5-MDMA, an NPS linked to severe intoxications, increased dopamine and serotonin levels in the nucleus accumbens shell and medial prefrontal cortex of rats in a dose-, brain area-, and age-dependent manner. In adult rats, dopamine rose more markedly in both brain areas, while adolescent rats showed a greater serotonin increase in the nucleus accumbens shell. The drug stimulated locomotion and stereotyped activity more in adolescents but did not trigger 50-kHz ultrasonic vocalizations, suggesting no positive affective properties. These findings indicate age-dependent neurochemical and behavioral effects, helping to assess health risks from human use.