REVIEW doi:10.1111/j.1360-0443.2011.03582.x A systematic review of methamphetamine precursor regulationsadd_3582 1..14 Rebecca McKetin1,2, Rachel Sutherland2, David A. Bright2 & Melissa M. Norberg2 Centre for Mental Health Research,The Australian National University, Canberra, Australia1 and National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia2 ABSTRACT Aims To assess the effectiveness of methamphetamine precursor regulations in reducing illicit methamphetamine supply and use. Methods A systematic review of 12 databases was used to identify studies that had evaluated the impact of methamphetamine precursor regulations on methamphetamine supply and/or use. The guidelines of the Effective Practice and Organization of Care Group (EPOC) of The Cochrane Collaboration were used to determine which study designs were included and assess their quality. Results Ten studies met the inclusion criteria. These studies evaluated 15 interventions (13 regulations and two related interdiction efforts), all of which were located in North America. Interventions had consistent impacts across various indicators of methamphetamine supply and use. Seven of the 15 interventions produced reductions in methamphetamine indicators (ranging from 12% to 77%). Two of the largest impacts were seen following interdiction efforts, involving the closure of rogue pharmaceutical companies. There was no evidence of a shift into other types of drug use, or injecting use, although the impact on the synthetic drug market was not examined. Null effects were related largely to the existence of alternative sources of precursor chemicals or the availability of imported methamphetamine. Conclusions Methamphetamine precursor regulations can reduce indicators of methamphetamine supply and use. Further research is needed to determine whether regu- lations can be effective outside North America, particularly in developing countries, and what impact they have on the broader synthetic drug market. Improved data on precursor diversion are needed to facilitate the evaluation of precursor regulations. Keywords amphetamine, law enforcement, methamphetamine, precursors, regulations, substance use, supply. Correspondence to: Rebecca McKetin, Centre for Mental Health Research, ANU College of Medicine, Biology and Environment, Building 63, Eggleston Road, The Australian National University, Canberra ACT 0200 Australia. E-mail: [email protected] Submitted 16 December 2010; initial review completed 15 March 2011; final version accepted 28 June 2011 INTRODUCTION of chemicals, many of which have legitimate uses, and which can be obtained from various sources (e.g. falsify- Methamphetamine is a highly addictive drug that affects ing import licences, theft from chemical companies, somewhere between 14 and 53 million people globally purchasing large quantities of cold-and-flu tablets from [1]. World-wide production of methamphetamine has pharmacies) [2,4,5]. The most common precursor been estimated at 290 tons per year, with a retail value of chemicals are pseudoephedrine and ephedrine, which around US$28 billion [2]. Less than 10% of this supply is are used as decongestants in various cold-and-flu medi- believed to be interdicted [1]. One of the difficulties con- cations. Other popular chemical starting points include trolling methamphetamine supply is the ease with which phenylpropanolamine (PPA) and phenyl-2-propanone the drug can be manufactured using readily available (P2P or phenylacetone) [4]. Precursor regulations also chemicals, and the lucrative nature of such ventures cover a range of so-called ‘essential chemicals’ that [1,3–5]. are needed in the manufacturing process [5]. The aim A major strategy to reduce methamphetamine supply of precursor regulations is to prevent the diversion of involves regulating the chemicals used in its manufacture chemicals from their legitimate uses into clandestine [4]. Methamphetamine can be synthesized from a range drug manufacture. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction Addiction 2 Rebecca McKetin et al. Recent research suggests that precursor regulations relevance by one author (R.S.). The eligibility of full-text can be effective, but the evidence is marred by inconsis- papers was subsequently assessed independently by two tencies [6–12]. Inconsistencies may arise because regu- authors (R.M. and D.B.), including those papers where lations are evaluated against different outcomes (e.g. relevance was unclear. Ties were broken by R.S. Unpub- arrests, hospital admissions, price, availability) [13], they lished papers were excluded. Studies also needed to meet vary in their nature (e.g. wholesale versus retail regula- minimum quality criteria (see ‘Quality assessment’). tions) [11] or there may be contextual factors that impact on their effectiveness (e.g. the availability of imported Quality assessment methamphetamine) [14]. Also, the impact of regulations is impermanent, being undermined by drug manufactur- The quality of each study was assessed independently ers’ propensity to seek out alternative sources of precur- by two authors (R.M. and D.B.) using the guidelines of sor chemicals [14]. Therefore, study designs need to be the Cochrane Effective Practice and Organization of sensitive to the transient impacts produced by precursor Care Group (EPOC) of The Cochrane Collaboration [16]. regulations [15]. Where necessary, authors were contacted to clarify This systematic review examines the evidence around the methodology of the study. Differences were resolved the effectiveness of methamphetamine precursor regula- though discussion and consensus. tions in reducing illicit methamphetamine supply and Studies were excluded from the analysis if they did not use, and it makes recommendations for future research meet the minimum inclusion criteria for an EPOC review in this area. [16]. That is, studies must have been a randomized controlled trial, a controlled clinical trial, a controlled before–after study or an interrupted time–series study. METHOD Interrupted time–series studies needed to have a clearly Search strategy defined point in time when the intervention occurred and at least three data points both before and after the Twelve electronic databases were searched with the assis- intervention [16]. tance of a librarian (CINCH-Health, Criminal Justice EPOC guidelines were also used to assess the quality Abstracts, EconLit, EMBASE, Google Scholar, JSTOR, of included studies. For interrupted time–series designs LegalTrac, MEDLINE, PAIS International, Project these guidelines covered the appropriateness of the Cork, PsychINFO, Scopus). All searches combined three analysis, the number of data points pre- and post- concept areas: methamphetamine or amphetamine, intervention, specification of the intervention shape, precursor chemicals and regulations. Search strategies assessment of the primary outcome, completeness of the were adapted for each database. When available, subject data set, reliability of the outcome measure, protection headings were exploded and combined. For example, against detection bias and protection against secular the MEDLINE search was: ‘methamphetamine’ (exp), changes. ‘amphetamine’ (exp), ‘amphetamines’ (exp); AND ‘precursor$’, ‘precursor chemical$’, ‘pre precursor$’, ‘proto precursor$’, ‘production$’, ‘ephedrine’ (exp), Data extraction ‘pseudoephedrine’ (exp), ‘phenylpropanolamine’ (exp); Study details were extracted using a standardized form AND ‘government regulation’ (exp), ‘legislation’ [17] covering study design, location, outcome measures, (exp), ‘drug legislation’ (exp), ‘law enforcement’ (exp), sample size, analysis, results and limitations. Data were ‘drug and narcotic control’ (exp). The search was extracted separately for each intervention and outcome restricted to English language articles published between measure. January 1970 and October 2010. We also hand-searched the latest editions of key journals and the reference lists of papers that were included in the review.The full search Intervention effects strategy and review protocol are available from the The strength of the evidence for interventions was based authors on request. on study quality, the number of outcome measures and the consistency of results for different outcome measures, Inclusion criteria the lack of change in comparison series and the size To be eligible for inclusion, studies must have examined of the intervention effect. The size of the intervention the impact of a regulation pertaining to chemicals used effect was described in a relative sense as being small in the manufacture of methamphetamine or amphet- (up to 20%), moderate (around 30–40%) or large amine. Outcomes needed to relate to methamphetamine (50+ %). Post-regulatory changes were as reported by use or supply. Article titles/abstracts were screened for the study authors. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction Addiction Methamphetamine precursor regulations 3 RESULTS • Precursor regulations were embedded within broader drug control legislations which often included sub- Quality assessment sidiary drug laws that may have contributed to inter- Twenty relevant studies were identified, of which only 10 vention effects. met the minimum EPOC inclusion criteria [6–12,18–20] • Regulations often had several implementation dates (Fig. 1). The two grey literature studies [21,22] were (for different aspects of the regulation) or they were excluded because these reports did not contain