Pharmacological reviews
June 1, 2011
Christopher W Cunningham, Richard B Rothman, Thomas E Prisinzano
109 citations
Salvinorin A, the psychoactive compound in the Salvia divinorum plant, activates kappa-opioid receptors (KOP) to produce its intense hallucinogenic effects, making it the first known non-nitrogenous opioid receptor agonist. Unlike classic hallucinogens such as LSD and mescaline, its effects do not involve the 5-HT(2A) receptor. Research into its structure has yielded receptor probes and tools to study its psychological effects. Salvinorin A shows therapeutic potential for treating pain, mood disorders, substance abuse, and gastrointestinal disturbances, and suggests that nonalkaloid compounds can serve as scaffolds for developing drugs targeting aminergic G-protein coupled receptors.
Pharmacological reviews
April 23, 2025
Benjamin R Cummins, Gerald B Billac, David E Nichols et al.
62 citations
Serotonin 5-HT2A receptors are found throughout the body and are most dense in brain cortical layer V. They are involved in normal physiology and neuropsychiatric diseases like schizophrenia. Atypical antipsychotics block these receptors, while psychedelic drugs such as psilocybin, dimethyltryptamine, and lysergic acid diethylamide activate them to produce lasting therapeutic effects in clinical trials for major depression and substance use disorders. The three main agonist scaffolds—tryptamines, ergolines, and phenylalkylamines—engage different amino acid residues in the receptor binding pocket, leading to functionally selective outcomes. Understanding these ligand-receptor interactions guides future drug discovery for optimized therapeutics.
Pharmacological reviews
October 1, 2022
Anna U Odland, Jesper L Kristensen, Jesper T Andreasen
23 citations
Psychedelic-assisted psychotherapy shows promise for treating mental health disorders, and research on 5-HT2AR agonist psychedelics has grown rapidly. In humans, these compounds alter consciousness and affect emotional, social, and self-referential information processing. The translational value of animal behavior studies is debated. In rodents, acute psychedelic treatment produces head twitches, disrupts sensorimotor gating, stimulates motor activity, inhibits exploration, and shows anxiolytic-like effects while inhibiting repetitive behavior. Effects on depression-like behaviors, cognitive function, and social interaction are discrepant. Lasting effects are sensitive to experimental protocols. Improving animal studies by assessing lasting effects, publishing negative findings, and relating behaviors to neuroplastic changes will enhance translational value.
Pharmacological reviews
May 1, 2025
Merel Dagher, Catherine M Cahill, Anne M Andrews
10 citations
Antidepressant use during pregnancy has limited adverse effects on fetal health and child development, particularly for SSRIs and SNRIs, while untreated maternal depression carries well-researched harms. Pregnancy alters drug disposition and metabolism, affecting both mother and fetus. The FDA advises caution due to a lack of safety studies, as pregnant individuals are often excluded from clinical trials. The review asserts that individuals should be counseled on risks and benefits of treatment, as withholding treatment has possible negative outcomes. Newer therapeutics like ketamine and κ-opioid receptor antagonists warrant further investigation for use during pregnancy.