{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:51:40Z","timestamp":1793105500313,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,9,3]]},"abstract":"<jats:p>\n                    <jats:italic>Salvia divinorum<\/jats:italic>\n                    , whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently,\n                    <jats:italic>S. divinorum<\/jats:italic>\n                    extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that Salvinorin A potently and selectively inhibited\n                    <jats:sup>3<\/jats:sup>\n                    H-bremazocine binding to cloned \u03ba opioid receptors. Salvinorin A had no significant activity against a battery of 50 receptors, transporters, and ion channels and showed a distinctive profile compared with the prototypic hallucinogen lysergic acid diethylamide. Functional studies demonstrated that Salvinorin A is a potent \u03ba opioid agonist at cloned \u03ba opioid receptors expressed in human embryonic kidney-293 cells and at native \u03ba opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    serotonin receptor, the principal molecular target responsible for the actions of classical hallucinogens. Salvinorin A thus represents, to our knowledge, the first naturally occurring nonnitrogenous opioid-receptor subtype-selective agonist. Because Salvinorin A is a psychotomimetic selective for \u03ba opioid receptors, \u03ba opioid-selective antagonists may represent novel psychotherapeutic compounds for diseases manifested by perceptual distortions (e.g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that \u03ba opioid receptors play a prominent role in the modulation of human perception.\n                  <\/jats:p>","DOI":"10.1073\/pnas.182234399","type":"journal-article","created":{"date-parts":[[2002,9,3]],"date-time":"2002-09-03T15:58:55Z","timestamp":1031068735000},"page":"11934-11939","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":694,"title":["Salvinorin A: A potent naturally occurring nonnitrogenous \u03ba opioid selective agonist"],"prefix":"10.1073","volume":"99","author":[{"given":"Bryan L.","family":"Roth","sequence":"first","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Baner","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Westkaemper","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Siebert","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenner C.","family":"Rice","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SeAnna","family":"Steinberg","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Ernsberger","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Rothman","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health Psychoactive Drug Screening Program, and Departments of Biochemistry, Psychiatry, Neurosciences, and Pharmacology and Nutrition, Case Western Reserve University Medical School, Cleveland, OH 44106; Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224; Department of Medicinal Chemistry, Medical College of Virginia, Richmond, VA 23298; The Salvia divinorum Research and..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,8,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.1994.10472441"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0379-0738(00)00180-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-8741(94)90116-3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","unstructured":"Koreeda M. 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