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      • Record: found
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      New psychoactive substances of natural origin: A brief review

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          Abstract

          Plant-based drugs of abuse are as old as recorded human history. Although traditional addictive substances, such as opium, cannabis and coca, have been controlled by the United Nations anti-drug conventions, many, if not most, natural plants with addictive or abuse liability remain elusive. Therefore, the United Nations Office on Drugs and Crime (UNODC) has warned the emerging threat from new psychoactive substances (NPS), which are mostly derived or modified from the constituents of natural origin. For example, synthetic cannabinoids and synthetic cathinones are derived from the cannabis and khat plant, respectively. In this review, we briefly discussed the chemistry, pharmacology and toxicology of five common NPS of natural origin, i.e., khat, kratom, salvia, magic mushroom and mandrake. Through the review, we hope that professionals and general public alike can pay more attention to the potential problems caused by natural NPS, and suitable control measures will be taken.

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          Pharmacological characterization of designer cathinones in vitro.

          LD Simmler, TA Buser, M Donzelli … (2013)
          Designer β-keto amphetamines (e.g. cathinones, 'bath salts' and 'research chemicals') have become popular recreational drugs, but their pharmacology is poorly characterized. We determined the potencies of cathinones to inhibit DA, NA and 5-HT transport into transporter-transfected HEK 293 cells, DA and 5-HT efflux from monoamine-preloaded cells, and monoamine receptor binding affinity. Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and other entactogens. Cathinone, methcathinone and flephedrone, similar to amphetamine and methamphetamine, acted as preferential DA and NA uptake inhibitors and induced the release of DA. Pyrovalerone and 3,4-methylenedioxypyrovalerone (MDPV) were highly potent and selective DA and NA transporter inhibitors but unlike amphetamines did not evoke the release of monoamines. The non-β-keto amphetamines are trace amine-associated receptor 1 ligands, whereas the cathinones are not. All the cathinones showed high blood-brain barrier permeability in an in vitro model; mephedrone and MDPV exhibited particularly high permeability. Cathinones have considerable pharmacological differences that form the basis of their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is probably associated with a considerable risk of addiction. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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            Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist.

            K Baner, Paul Ernsberger, B Roth … (2002)
            Salvia divinorum, 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, S. divinorum 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 (3)H-bremazocine binding to cloned kappa 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 kappa opioid agonist at cloned kappa opioid receptors expressed in human embryonic kidney-293 cells and at native kappa opioid receptors expressed in guinea pig brain. Importantly, Salvinorin A had no actions at the 5-HT(2A) 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 kappa opioid receptors, kappa 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 kappa opioid receptors play a prominent role in the modulation of human perception.
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              Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study.

              John Huber, Peter M Benz, Ulrike Grimberg … (2004)
              Serotonin (5-Hydroxytryptamine, 5-HT) receptors play an important role in perception, affect regulation and attention. Pharmacological challenge with the 5-HT(2A) agonist psilocybin (PY) is useful in studying the neurobiological basis of cognition and consciousness. Investigation of dose-dependent effects of PY on psycho(patho)logical and physiological parameters. Eight subjects received placebo (PL), and 45 ("very low dose, VLD"), 115 ("low dose, LD"), 215 ("medium dose, MD"), and 315 ("high dose, HD") microg/kg body weight PY. The "Altered States of Consciousness Rating Scale" (5D-ASC), the "Frankfurt Attention Inventory" (FAIR), and the "Adjective Mood Rating Scale" (AMRS) were used to assess the effects of PY on psycho(patho)logical core dimensions, attention, and mood. A 24-h electrocardiogram (EKG) was recorded and blood pressure was measured. Plasma concentrations of thyroid-stimulating hormone (TSH), prolactin (PRL), cortisol (CORT), adrenocorticotropic hormone (ACTH), and standard clinical chemical parameters were determined. PY dose dependently increased scores of all 5D-ASC core dimensions. Only one subject reacted with transient anxiety to HD PY. Compared with PL, MD and HD PY led to a 50% reduction of performance in the FAIR test. "General inactivation", "emotional excitability", and "dreaminess" were the only domains of the AMRS showing increased scores following MD and HD PY. The mean arterial blood pressure (MAP) was moderately elevated only 60 min following administration of HD PY. Neither EKG nor body temperature was affected by any dose of PY. TSH, ACTH, and CORT plasma levels were elevated during peak effects of HD PY, whereas PRL plasma levels were increased following MD and HD PY. PY affects core dimensions of altered states of consciousness and physiological parameters in a dose-dependent manner. Our study provided no cause for concern that PY is hazardous with respect to somatic health.
              Article 0 comments Cited 111 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Food Drug Anal
                Journal ID (iso-abbrev): J Food Drug Anal
                Title: Journal of Food and Drug Analysis
                Publisher: Taiwan Food and Drug Administration
                ISSN (Print): 1021-9498
                ISSN (Electronic): 2224-6614
                Publication date (Electronic, collection): 2017
                Publication date (Electronic, pub): 18 April 2017
                Volume: 25
                Issue: 3
                Pages: 461-471
                Affiliations
                [a ]Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
                [b ]School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
                [c ]College of Pharmacy, Duksung Women's University, Seoul, South Korea
                [d ]Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, South Korea
                [e ]Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
                Author notes
                [* ]Corresponding author. School of Pharmacy and Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung City, 80708, Taiwan. Fax: +886 7 3210683.
                [** ]Corresponding author. Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, 99- Daehak-ro, Yuseongk-gu, Daejeon, 305-764, South Korea. Fax: +82 42 821 8541. E-mail addresses: hschung@ 123456cnu.ac.kr (H. Chung), jhlitox@ 123456kmu.edu.tw (J.-H. Li).
                Article
                Publisher ID: jfda-25-03-461
                DOI: 10.1016/j.jfda.2017.04.001
                PMC ID: 9328809
                PubMed ID: 28911631
                SO-VID: 5e888045-c1ea-43fd-ac7b-8711e955e138
                Copyright © © 2017 Taiwan Food and Drug Administration
                License:

                This is an open access article under the CC-BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 27 October 2016
                Date revision received : 16 March 2017
                Date accepted : 04 April 2017
                Funding
                Funded by: Ministry of Science and Technology, Taiwan
                Award ID: MOST 103-2923-B-037-001-MY2
                Funded by: Kaohsiung City Government
                Award ID: T105004
                This work was supported in part by grants from the Ministry of Science and Technology, Taiwan (MOST 103-2923-B-037-001-MY2) and Kaohsiung City Government (T105004).
                Categories
                Subject: Review Article

                Keywords: new psychoactive substances (nps),khat,kratom,salvia,magic mushroom,mandrake
                Data availability:
                Keywords: new psychoactive substances (nps), khat, kratom, salvia, magic mushroom, mandrake

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