N S N O O O N N N N O N DRUG ADULTERANTS AND N N THEIR EFFECTS ON THE O N HEALTH OF USERS: A CRITICAL REVIEW N N O CICAD Luis Almagro Farah Urrutia Secretary General Secretary for Multidimensional Security Organization of American States Organization of American States Nestor Mendez Adam E. Namm Assistant Secretary General Executive Secretary Organization of American States Inter-American Drug Abuse Control Commission Organization of American States OAS Cataloging-in-Publication Data Inter-American Drug Abuse Control Commission. Inter-American Observatory on Drugs. Adulterantes de las drogas y sus efectos en la salud de los usuarios: una revisión crítica / [Observatorio Interamericano sobre Drogas (OID) de la Comisión Interamericana para el Control del Abuso de Drogas (CICAD]. v. ; cm. (OAS. Documentos oficiales ; OEA/Ser.L/XIV.6.71) ISBN 978-0-8270-6872-8 1. Drug abuse--Health aspects. 2. Substance abuse--Health aspects. 3. Drug adulteration. 4. Psychotropic drugs. 5. Designer drugs. I. Title. II. Organization of American States. Secretariat for Multidimensional Security. III. Series. OEA/Ser.L/XIV.6.71 COPYRIGHT© (2019) Organization of American States. All the rights reserved under International and Panamerican Conventions. No portion of the content of this material may be reproduced or transmitted in any form, nor by any electronic or mechanical means, totally or partially, without the express consent of the Organization. Prepared and published by the Inter-American Drug Abuse Control Commission (CICAD), Organization of American States (OAS), Report on Drug Use in the Americas 2019, Washington, D.C., 2019. Comments on the report are welcome and can be sent to: [email protected] The contents expressed in this document are presented exclusively for informational purposes and do not necessarily represent the opinion or official position of the Organization of American States, its General Secretariat or its member states. DRUG ADULTERANTS AND THEIR EFFECTS ON THE HEALTH OF USERS: A CRITICAL REVIEW Overall coordination of the document: M.H.S. Marya Hynes. Head of the Inter-American Observatory on Drugs (OID) of the Inter-American Drug Abuse Control Commission (CICAD), Organization of American States (OAS). Thom Browne. CEO, Colombo Plan Secretariat. Primary author: Dr. Antonio Pascale Prieto, M.D., Specialist in Clinical Toxicology. Associate Professor of Clinical Toxicology, Montevideo, Uruguay. Member of REDLA (Network of Latin American Drug Researchers). Consultants for Brazil (tables and summaries of selected studies): Dr. Alice A. da Matta Chasin, Ph.D. in Toxicology from the University of São Paulo. Full Professor of Toxicology in the Oswaldo Cruz School; Expert in Forensic Toxicology, 1976-2004; Visiting Professor at the University of São Paulo, 2003-2014; Representative of TIAFT in Brazil, 1995-2018. Natália Giancotti Ferreira, Criminal Expert of the state of São Paulo, Brazil. Degree in Pharmacy and a Master of Science from the Postgraduate Program in Toxicology, Ribeirão Preto School of Pharmaceutical Sciences of the University of São Paulo. Consultant for bibliographical search and tables: Dr. Federico Pose Mazzella, M.D., Resident in Clinical Toxicology, Montevideo, Uruguay. Conflict of interest: The authors of this paper hereby state that they have no conflict of interest. DRUG ADULTERANTS AND THEIR EFFECTS ON THE HEALTH OF USERS: A CRITICAL REVIEW KEY POINTS: • The purity of drugs is highly variable and depends on the region or epidemiological context. Evidence shows that there is a broad spectrum of adulterants in the drugs that are most prevalent worldwide. • Drug adulteration is constantly changing, with an overall trend toward a decline in the purity of most drugs over the past 10 years. Some adulterants enhance the psychoactive effects of a drug and may contribute to its addictive potential. • Some adulterants are associated with a significant increase in the risk of overdose and death due to acute poisoning (e.g., fentanyl in cocaine or heroin, adulterants in MDMA and LSD, adulterations of new psychoactive substances or NPS); others are related to complications that appear following chronic use in subjects who may be genetically predisposed (e.g., levamisole in cocaine). • Deaths in the studies examined appear to be related to the drugs involved, to poly-drug use, and to the dose consumed. • Considering the gaps in knowledge, it would seem necessary to conduct a standardized analysis of chemical composition and expand it to include a broader spectrum of substances, using similar protocols with more representative samples in the various countries and regions, to obtain a complete chemical characterization of the drugs analyzed. • The quality of the information and evidence available on the harms to health caused by some adulterants varies widely. While the most common adulterations of some substances are well known, the emergence of NPS has led to gaps in knowledge about the drugs being used and their composition. • Coordination among supply control agencies and those organizations that have access to samples obtained directly from users appears to be needed to achieve common objectives. Early warning systems in the different countries are fundamental to such coordination. • In the current context of legalization or regularization of the marijuana market in a number of countries, more rigorous research must be conducted on possible 1 contamination by pesticides used on crops, and their possible effects on cannabis use -- particularly smoked cannabis, given current evidence linking adulterations of marijuana with respiratory disease. • Studies of the toxic health effects of adulterants and their association with the drug that is used are based on experimental studies, and essentially on case reports and case series. Epidemiological context, clinical presentation, complications (as seen clinically and in histopathology), and analytical confirmation are the basic pillars in analyzing the toxicity of an adulterant or an adulterant/drug combination. • Health professionals, the community, and most importantly drug users should be aware of the risks inherent in the adulterations of the drugs they are using, as well as the potential chronic, long-term toxic effects that may be attributable to the presence of one or more adulterants. • Hospitals need to have trained personnel, the necessary material resources, and the means to communicate immediately with local laboratories to identify the adulterants. Early diagnosis makes for better treatment and reduces morbidity and mortality. • To address this public health problem, it is necessary to develop research and action protocols and to strengthen networks involving government agencies (e.g., early warning systems), clinical and forensic laboratories, and nongovernmental organizations with access to users, as well as universities and toxicology centers. 2 Contents 1. INTRODUCTION ......................................................................................................................... 5 2. OBJECTIVES OF THIS STUDY ...................................................................................................... 7 2.1. Overall objective: ............................................................................................................... 7 2.2. Specific objectives: ............................................................................................................. 7 3. METHODOLOGY ........................................................................................................................ 7 3.1. Systematic review .............................................................................................................. 8 3.2. Descriptive review .............................................................................................................. 9 4. ADULTERANTS FOUND IN THE DRUGS TESTED ....................................................................... 11 4.1. Cocaine and its derivatives (cocaine hydrochloride, smokable cocaines) ....................... 11 4.1.1. Presence of adulterants in South America ................................................................ 12 4.1.2. Studies and analyses reported in Europe .................................................................. 31 4.1.3. Analysis of seizures in Africa ..................................................................................... 36 4.1.4. Alerts to presence of fentanyl and derivatives in seizures of cocaine ...................... 36 4.2. Amphetamine-type stimulants (ATS) and NPS ................................................................. 36 4.2.1. The situation in Europe ............................................................................................. 39 4.2.2. United States ............................................................................................................. 41 4.2.3. South America ........................................................................................................... 41 4.2.4. Asia and Oceania ....................................................................................................... 43 4.3. Derivatives of opium, heroin, synthetic opioids (fentanyl and derivatives) .................... 44 4.3.1. Opium ........................................................................................................................ 44 4.3.2. Analysis of samples of heroin .................................................................................... 45