Autism spectrum disorder (ASD) involves social communication deficits and repetitive behaviors, with no approved drugs for its core symptoms. Existing medications like aripiprazole and risperidone treat irritability but can cause side effects such as weight gain and sedation. Drugs with pro-social effects, including MDMA and its analogue MBDB, may help address social anxiety and avoidance in ASD. This review examines the pharmacology of methylenedioxy amphetamine analogues (MDXX drugs), focusing on their binding sites, metabolism, and structure-activity relationships. It emphasizes how individual stereoisomers and their racemic mixtures shape drug effects. The authors propose that MDXX compounds offer a promising chemical space for developing safer, more effective treatments for ASD.
A single dose of the psychedelics LSD or DOI did not reduce opioid consumption or withdrawal signs in mice that had become dependent on fentanyl analogs. Mice drinking water avoided the bitter taste of quinine, but mice consuming fentanyl solutions continued drinking despite the adulteration, a behavior unchanged by psychedelic treatment. Fifteen days later, neither LSD nor DOI altered naloxone-precipitated jumping or restlessness, but both drugs lessened withdrawal-associated heightened sensitivity to heat. These results do not support a single psychedelic exposure as a treatment for opioid use disorder, though they suggest possible persistent effects on pain perception during withdrawal.
Novel arylcyclohexylamine (ACX) analogs of PCP, PCE, and ketamine, which appear on the illicit market, show PCP-like abuse liability and varied toxicities. In mice, PCP-like ACXs were more effective locomotor stimulants than amphetamines, while ketamine-like ACXs were less effective. Adding -Cl, -OH, or -OMe at the 3-position did not affect locomotor effectiveness, but 4-OMe reduced it. Drugs with -OH at the 3-position or -OMe at the 3- or 4-position induced lethal effects. All novel ACXs partially substituted for PCP in rats, and PCP and 3-Cl-PCP caused dose-dependent psychosis-like neurocognitive deficits not seen with cocaine or morphine.