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Dipartimento del Farmaco Istituto Superiore di Sanità - Roma Smar tDrugs English Edition OSSERVATORIO O S S F A D FUMO ALCOL E DROGA www.iss.it/ofad The project was carried out with the technical and logistical support of the Italian Anti-adulteration and Safety Bureau (Carabinieri per la tutela della Salute-NAS) in (cid:91)(cid:79)(cid:76)(cid:3)(cid:90)(cid:91)(cid:72)(cid:78)(cid:76)(cid:3)(cid:86)(cid:77)(cid:3)(cid:80)(cid:75)(cid:76)(cid:85)(cid:91)(cid:80)(cid:196)(cid:74)(cid:72)(cid:91)(cid:80)(cid:86)(cid:85)(cid:3)(cid:86)(cid:77)(cid:3)(cid:58)(cid:84)(cid:72)(cid:89)(cid:91)(cid:3)(cid:58)(cid:79)(cid:86)(cid:87)(cid:90)(cid:3)(cid:72)(cid:85)(cid:75)(cid:3)(cid:94)(cid:76)(cid:73)(cid:90)(cid:80)(cid:91)(cid:76)(cid:90)(cid:3)(cid:72)(cid:85)(cid:75)(cid:3)(cid:80)(cid:85)(cid:3)(cid:91)(cid:79)(cid:76)(cid:3)(cid:90)(cid:92)(cid:87)(cid:87)(cid:83)(cid:96)(cid:3)(cid:86)(cid:77)(cid:3)(cid:90)(cid:92)(cid:73)- stances to be analyzed Drug abuse and Doping Unit Italian Observatory on Tobacco, Alcohol and Drugs of Abuse Department of Therapeutic Research and Medicines Evaluation Istituto Superiore di Sanità Viale Regina Elena, 299 - 00161 Roma Tel. 06 49902909 Fax 06 49902016 E-mail: [email protected] Finito di stampare nel mese di luglio 2011 Project funded by the da: De Vittoria srl “ Fondo per le Politiche Giovanili - anno 2010” Via degli Aurunci, 19 - Roma Smar tDrugs English Edition Simona Pichini with Emilia Marchei, Ilaria Palmi, Manuela Pellegrini, (cid:53)(cid:82)(cid:69)(cid:72)(cid:85)(cid:87)(cid:68)(cid:3)(cid:51)(cid:68)(cid:70)(cid:76)(cid:192)(cid:70)(cid:76)(cid:15)(cid:3)(cid:51)(cid:76)(cid:72)(cid:85)(cid:74)(cid:76)(cid:82)(cid:85)(cid:74)(cid:76)(cid:82)(cid:3)(cid:61)(cid:88)(cid:70)(cid:70)(cid:68)(cid:85)(cid:82) Department of Therapeutic Research and Medicine Evaluation Italian Observatory on Tobacco, Alcohol and Drugs of Abuse ISS - Rome In cooperation with Gioacchino Calapai, Alessandro Oteri, Viviana Cafeo, Achille Patrizio Caputi Department of Clinical and Experimental Medicine and Pharmacology University of Messina and with Julia Klein Drug Testing Consultants Toronto, Canada Working Group of Italian Observatory on Tobacco, Alcohol an Drugs Abuse Antonella Bacosi, Giordano Carosi, Simonetta Di Carlo, Rita di Giovannandrea, Alessandra Di Pucchio, Patrizia Gori, Laura Martucci, Luisa Mastrobattista, Monica Mazzola, Gabriele Modigliani, Claudia Mortali, Enrica Pizzi, Maria Concetta Rotolo, Giulia Scaravelli, Renata Solimini, Roberta Spoletini Index Introduction to the Second Edition pag. 3 Amanita muscaria pag. 7 Areca catechu pag. 14 Argemone mexicana pag. 24 Argyreia nervosa pag. 32 Artemisia absinthium pag. 38 Ayahuasca pag. 46 Brugmansia arborea pag. 53 Calea zacatechichi pag. 58 Citrus aurantium pag. 61 Datura stramonium pag. 69 Ephedra sinica pag. 75 Ipomoea violacea pag. 85 Lactuca virosa pag. 89 Mimosa hostilis pag. 94 Mitragina speciosa pag. 97 Muira puama pag. 103 Pausinystalia yohimbe pag. 105 Piper methysticum pag. 113 Rivea corymbosa pag. 119 Salvia divinorum pag. 124 Sceletium tortuosum pag. 130 Sida cordifolia pag. 135 Tribulus terrestris pag. 142 Trichocereus macrogonus pag. 146 Trichocereus pachanoi pag. 146 Trichocereus peruvianus pag. 146 SmartDrugs Trichocereus validus pag. 146 Trichocereus werdermannianus pag. 147 Turnera aphrodisiaca pag. 154 Voacanga africana pag. 161 Withania somnifera pag. 168 Spices pag. 175 Synthetic cannabinoids pag. 177 Canavalia maritima pag. 182 Leonotis leonurus pag. 185 Leonurus sibiricus pag. 188 Nelumbo nucifera pag. 192 Nymphaea alba pag. 196 Nymphaea caerulea pag. 198 Pedicularis densiflora pag. 201 Scutellaria nana pag. 204 Zornia latifolia pag. 207 Introduction The terminology “Smart-Drugs“ includes all legal compounds of natural or synthetic origin, not prohibited by various drug laws in different countries. The drugs may contain active compounds with known or presumed psychoactive prop- erties (1). The definition of “Smart Drugs“ is changing continuously, not only by including different types of substances that fall into this category, but also from a conceptual and cultural point of view. In the 90s’ the term “Smart Drugs“ spread in the United States referring to some drugs used as adjuvants in diseases such as senility. In 1991, the book “Smart Drugs and Nutrients”, written by the American gerontologist Ward Dean and by the journalist John Morgenthaler described dozens of substances with “brain action” or “nootropics” which reportedly in- creased mental performance and sexual potency (2). Only a few of the products of plant origin were mentioned in the book. Indeed, the “American” definition of “Smart Drugs“did not change over time: it still deals with a series of pharmacologi- cally active substances including steroids, which have an impact on the general “performance” of the individual. On the other hand, at the end of the 90’s a tendency spread in Europe among high school and university students to use natural or synthetic substances which could be legally purchased and were considered helpful in improving concentra- tion and memory due to real or perceived psychoactive properties. Currently, there is no unique terminology for the term “Smart Drugs” because they can refer simultaneously to plant drugs, ethnic drugs, ethnobotanical drugs, natural drugs, biodrugs, etc. For some people, the term “Smart Drug” indi- cates a series of energy drinks or stimulating pills (which attempt to simulate the effect of “ecstasy”) which guarantee stimulating effects while remaining within legality (caffeine, ginseng, etc..): they are proposed and consumed especially in youth circles (clubs, raves etc...). As above-reported, the “Smart Drugs” are generally not included in the list of illicit drugs as per the Laws banning the sale of such substances (in Italy, the Article 14 of Republic Presidential Decree 309/90 and subsequent updates) (3). However, the active compound/compounds contained in the fresh or dry parts of the plants marketed as “Smart Drugs“ may be in- cluded in this list, while, neither the plant, nor parts of it are, making them automatically legal. In fact, for the past fifteen years there have been legal “Smart Shops”, in different European countries specializing in the sale of herbal products of different origin or formulation. There are about one hundred “Smart Shops”, in Italy which sell not only natural and syn- thetic “Smart Drugs” (the latter such as amino acid containing capsules, GABA type neurotransmitters , etc) with the seal of the European Council, but they also sell products for the cultivation of the plants (mostly mushrooms and hemp) and accessories used to optimize the effect of the smoked substances (cigarette papers, filters, pipes, water pipes, vaporizers). In addition, these products are considered “smart” because they can be acquired through the internet web sites as incense and home scents with precise indications: “not for human consumption”, although there are specific websites which ex- plain in great detail different types of administration routes (ingestion, smoking of the dry plant etc) of these products. The heterogeneity of “Smart Drugs” is reflected by a multitude of classification criteria: method of use, chemical class to which the active principles belong, purpose of use etc. Most of these substances, extracted from herbs, were originally consumed in the alternative ethnic medicine, being at the centre of traditional commemorative rites and customs. The so called primitive peoples knew very well the dangers associated with the use of these plants and considered them sacred. “Sacred” derives in fact from the Latin sacer and indicates “from which you may stay far away.” Starting from 2003, on behalf of the Minister of Health, the “Drug of abuse and doping” Unit of the Italian Institute of Health carried out more than 500 quali-quantititative analyses and pharmaco-toxicological evaluation on more than 200 products seized by the Italian Carabinieri police force and by the public prosecutors’ offices in different cities. These products come from “Smart Shops”, herbalist’s shops, ethnobotany shops, e-commerce and they usually are packages containing dried plant extracts with different names, labels and casings. The analysis and classification of these substances is ongoing. In 2005, the Italian Institute of Health, asked by the Department for Anti-drug Policies, prepared a book of monographs for the most common 25 “Smart Drugs” considered at risk of drug-dependence and intoxication for the reported pharma- cological and subjective effects(4). 3 SmartDrugs In each monograph, the taxonomic characteristics of the plant were given including a list of the active compounds, in which parts of the plant the active compounds are concentrated and the geographical origin of the plant. The physico- chemical characteristics of the active compounds as well as the historical and current use were also highlighted. Informa- tion about the legislation for possession and use of each of these plants as well as of their active compounds in different countries was also given. In addition, the pharmacological and toxicological properties of the active compounds were listed. Finally, in each monograph it was also possible to obtain information on the operating procedure to follow for set- ting up the analytical determination of active components in biological fluids of consumers or in plant parts. The book was neither listing nor organizing all the plant products available in “Smart Shops”, but aimed to alert the in- terested people and law enforcement agencies about some plants containing real or presumed psychoactive compounds (stimulants, hallucinogens,”aphrodisiacs, etc.) whose consumption could be harmful in one way or other. The book on “Smart Drugs” published by the Italian Institute of health had a large circulation in the scientific world as well as in the mass media. But, as mentioned, in the recent years the trend in use and consumption of these substances has changed, as some websites have revealed. Moreover, new “Smart Drugs” have been introduced and new scientific information about their use and toxicity appeared in the international literature. Therefore, in this new edition, six new “Smart Drugs” have been added and the monographs of the old ones have been updated with new information concerning legislation, pharmacological properties and analytical methodologies for determination of active principles in biological fluids of eventual consumers, or in the plant parts. Special attention has been paid to “Spice”, mixtures of different “Smart Drugs”, which have aroused the interest for the pharmacological and toxicological actions due to the presence of several products of plant origin and synthetic substances with effects similar to those of cannabis. Although not exhaustive, the data presented in this second Edition of the “Smart Drugs“ book originates from the most recent international literature and investigations from our group and provide useful information for investigators, legisla- tors and law enforcement agencies. 4 Introduzione References 1. BAKER LS. “Smart drugs”: a caution to everybody. Am J Psychiatry. 1996; 153: 844-845. 2. DEAN W, MORGENTHALER J. Smart Drugs and Nutrients: how to improve your memory and increase your intelligence using the latest discoveries in neuroscience. Smart Publications - Petaluma, CA USA 1990. 3. Decreto del Presidente della Repubblica (D.P.R.) n. 309 del 9 ottobre 1990 e suo testo aggiornato nel 2006 e presente nella Gazzetta Ufficiale n. 62 del 15 marzo 2006. 4. PICHINI S, PALMI I, MARCHEI E, PELLEGRINI M, PACIFICI R, ZUCCARO P. Smart Drugs. Osservatorio Fumo, Alcol e Droga, Dipartimento del Farmaco, Istituto Superiore di Sanità; ottobre 2006. Symbols and abbreviations CAS: Chemical Abstract Service, a division of the American Chemical Society, which assigns a numerical identifier that individualizes in an unequivocal way each chemical substance described in literature. ED50: the amount of active ingredient efficacious in 50% of the participants in an experiment. LD: the amount of active ingredient lethal in the participants in an experiment. LD50: the amount of active ingredient lethal in 50% of the participants in an experiment. LDLo: the minimum amount of lethal active ingredient in the participants in an experiment. TDLo: the minimum amount of active ingredient toxic for the participants in an experiment. UVmax: the wavelength corresponding to the maximum absorbance of a chemical compound. IC50: the concentration of an inhibitor where the response (or binding) is riduced by half. 5

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Most of these substances, extracted from herbs, were originally .. containing Amanita muscaria by gas chromatography-mass spectrometry (GC-MS) Arecoline is the principal alkaloid of the Areca catechu, the other three substances are
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