Frontiers in pharmacology
January 1, 2023
Leah M Salinsky, Christina R Merritt, Joshua C Zamora et al.
14 citations
Opioid misuse and overdose deaths are a major public health problem involving prescription opioids and potent fentanyl derivatives. Repeated overdose events indicate opioid use disorder (OUD). Opioids reduce pain by activating µ-opioid receptors (MOR) in the central nervous system, and dysregulation of reward circuitry underlies OUD. Serotonin (5-HT) contributes to opioid pharmacology and OUD. There is renewed interest in psychedelic compounds acting through the 5-HT2A receptor (5-HT2AR) for treating substance use disorders. Emerging data suggest MOR and 5-HT2AR crosstalk at cellular levels and in OUD circuitry, offering opportunities for novel pharmacological intervention. This review discusses the opportunities and challenges of using 5-HT2AR agonists as therapeutics for OUD.
Psychopharmacology
August 1, 2025
Leah M Salinsky, Christina R Merritt, Erik J Garcia et al.
8 citations
A single dose of the psychedelic compound (-)-DOI, which activates the 5-HT2A serotonin receptor, reduced cocaine intake and motivation for cocaine in male rats. The drug made cocaine less rewarding and made rats more sensitive to price increases, effectively devaluing the drug. Blocking the 5-HT2A receptor with M100907 eliminated these effects, confirming the receptor's role. The findings suggest that 5-HT2A receptor-acting psychedelics may hold promise for reducing cocaine use, warranting further preclinical research into their effects on intake and relapse.
Addiction biology
March 1, 2026
Leah M Salinsky, Kyra C Diaz, Joshua L Fox et al.
1 citation
Polysubstance use of opioids and stimulants is common, but most research examines each drug alone. In rats, the effects of fentanyl and methamphetamine—alone or combined—on movement sensitization and social behavior depended on drug class, drug history, and sex. After withdrawal, social deficits emerged. A single dose of the psychedelic DOI reversed those social deficits and even boosted social interaction in females. The findings suggest psychedelics might help treat social impairments linked to withdrawal from combined opioid and stimulant use.
Research square
April 23, 2026
Leah M Salinsky, Joshua L Fox, Kyra C Diaz et al.
Withdrawal from repeated use of methamphetamine and fentanyl together reduces social preference in rats, confirming earlier findings that polysubstance withdrawal impairs social behavior. A single dose of psilocybin did not restore sociability within 24 hours. In the medial prefrontal cortex, psilocybin had opposite effects on CRHR1 gene expression depending on drug history: it decreased expression in control rats but increased it in polysubstance-treated rats. In the nucleus accumbens, polysubstance treatment reduced CRHR1 expression. OPRM1 expression was sex-dependent, with a marked reduction in the nucleus accumbens of females after polysubstance treatment and sex-dependent effects in the medial prefrontal cortex.