Essential/precursor chemicals and drug consumption: impacts of US sodium permanganate and Mexico pseudoephedrine controls on the numbers of US cocaine and methamphetamine users.

BACKGROUND AND AIMS: In December 2006 the United States regulated sodium permanganate, a cocaine essential chemical. In March 2007 Mexico, the United States' primary source for methamphetamine, closed a chemical company accused of illicitly importing 60+ tons of pseudoephedrine, a methamphetamine precursor chemical. US cocaine availability and methamphetamine availability, respectively, decreased in association. This study tested whether the controls had impacts upon the numbers of US cocaine users and methamphetamine users. DESIGN: Auto-regressive integrated moving average (ARIMA) intervention time-series analysis. Comparison series-heroin and marijuana users-were used. SETTING: United States, 2002-14. PARTICIPANTS: The National Survey on Drug Use and Health (n = 723 283), a complex sample survey of the US civilian, non-institutionalized population. MEASUREMENTS: Estimates of the numbers of (1) past-year users and (2) past-month users were constructed for each calendar quarter from 2002 to 2014, providing each series with 52 time-periods. FINDINGS: Downward shifts in cocaine users started at the time of the cocaine regulation. Past-year and past-month cocaine users series levels decreased by approximately 1 946 271 (-32%) (P < 0.05) and 694 770 (-29%) (P < 0.01), respectively-no apparent recovery occurred through 2014. Downward shifts in methamphetamine users started at the time of the chemical company closure. Past-year and past-month methamphetamine series levels decreased by 494 440 (-35%) [P < 0.01; 95% confidence interval (CI) = -771 897, -216 982] and 277 380 (-45%) (P < 0.05; CI = -554 073, -686), respectively-partial recovery possibly occurred in 2013. The comparison series changed little at the intervention times. CONCLUSIONS: Essential/precursor chemical controls in the United States (2006) and Mexico (2007) were associated with large, extended (7+ years) reductions in cocaine users and methamphetamine users in the United States.

US federal cocaine essential ('precursor') chemical regulation impacts on US cocaine availability: an intervention time-series analysis with temporal replication.

BACKGROUND AND AIMS: Research shows that essential/precursor chemical controls have had substantial impacts on US methamphetamine and heroin availability. This study examines whether US federal essential chemical regulations have impacted US cocaine seizure amount, price and purity-indicators of cocaine availability. DESIGN: Autoregressive integrated moving average (ARIMA)-intervention time-series analysis was used to assess the impacts of four US regulations targeting cocaine manufacturing chemicals: potassium permanganate/selected solvents, implemented October 1989 sulfuric acid/hydrochloric acid, implemented October 1992; methyl isobutyl ketone, implemented May 1995; and sodium permanganate, implemented December 2006. Of these chemicals, potassium permanganate and sodium permanganate are the most critical to cocaine production. SETTING: Conterminous United States (January 1987-April 2011). MEASUREMENTS: Monthly time-series: purity-adjusted cocaine seizure amount (in gross weight seizures < 6000 grams), purity-adjusted price (all available seizures), and purity (all available seizures). DATA SOURCE: System to Retrieve Information from Drug Evidence. FINDINGS: The 1989 potassium permanganate/solvents regulation was associated with a seizure amount decrease (change in series level) of 28% (P < 0.05), a 36% increase in price (P < 0.05) and a 4% decrease in purity (P < 0.05). Availability recovered in 1-2 years. The 2006 potassium permanganate regulation was associated with a 22% seizure amount decrease (P < 0.05), 100% price increase (P < 0.05) and 35% purity decrease (P < 0.05). Following the 2006 regulation, essentially no recovery occurred to April 2011. The other two chemical regulations were associated with statistically significant but lesser declines in indicated availability. CONCLUSIONS: In the United States, essential chemical controls from 1989 to 2006 were associated with pronounced downturns in cocaine availability.

Hazardous birthday drinking among young people: population-based impacts on emergency department and in-patient hospital admissions.

BACKGROUND AND AIMS: There is growing concern about the possible adverse health impacts of binge drinking during birthday celebrations among adolescents and young adults. We estimate the impacts of birthday alcohol use on adolescent and young adult in-patient/emergency department (ED) hospital admissions. DESIGN: We employed Autoregressive Integrated Moving Average (ARIMA) intervention analysis to assess whether the rate of ICD-10 alcohol-use-disorder (AUD) events per 1000 in-patient/ED admissions increased significantly during birthday weeks. SETTING: All in-patient/ED admissions in Ontario, Canada from 1 April 2002 to 31 March 2007. PARTICIPANTS: Individuals aged 12-30 years. MEASUREMENTS: AUD events per 1000 in-patient/ED admissions by age in weeks. FINDINGS: Multiple increases were found. The largest occurred during the birthday week of 19 years of age, the beginning of the minimum legal drinking age (MLDA) in Ontario: AUD admission rates increased (spiked) by 38.30 per 1000 total admissions [95% confidence interval (CI) = 34.66-41.94] among males (a 114.3% increase over baseline), and by 28.13 (95% CI = 25.56-30.70) among females (a 164.0% increase). Among both genders, the second largest birthday-week spikes occurred during ages 20-22 years, followed by somewhat lower but still pronounced birthday-week spikes during ages 23-26 years and 30 years (all these spikes: P < 0.05). Birthday-week spikes occurred as early as age 16 years for males and 14 years for females (both spikes: P < 0.05). CONCLUSIONS: There appears to be an increase in alcohol-related adverse events from drinking around the time of one's birthday among young adults in Canada.

Essential ("precursor") chemical control for heroin: impact of acetic anhydride regulation on US heroin availability.

BACKGROUND: To reduce heroin availability, the United Nations (UN) has encouraged nations to control acetic anhydride, an essential ("precursor") chemical typically necessary to the drug's production. This effort, a major environmental prevention policy, has received little evaluation. The United States, per the UN's lead, implemented acetic anhydride regulation in 11/1989. The present study examines whether the US regulation impacted US heroin availability. METHODS: Monthly series of three heroin availability indicators-heroin purity, heroin price, and amount of heroin seized-were constructed for the conterminous United States, the US Southwest (supplied predominantly with Mexican-produced heroin), and the US Northeast (supplied predominantly, at the time, with Southeast Asian-produced heroin). Data came from the System to Retrieve Information from Drug Evidence (01/1987-04/2011). Impacts were assessed using ARIMA-intervention time series analysis. RESULTS: In each US area, heroin purity and amount seized rose and price decreased throughout the pre-intervention period. All of the indicators then reversed course at the time of the regulation. In the conterminous United States, the US Northeast, and the US Southwest, purity decreased (-40%, -25% and -50%, respectively); amount seized decreased (-27%, -37% and -39%, respectively); and price rose (+93%, +102% and +296%, respectively). Impacts lasted 2-5 years. CONCLUSION: US heroin availability decreased in association with the US acetic anhydride regulation. The impacts in the US Southwest and US Northeast suggest that heroin production in Mexico and Southeast Asia, respectively, was constrained. This study lends support to the contention that essential ("precursor") chemical control can be used to help address heroin.

Mexico's precursor chemical controls: emergence of less potent types of methamphetamine in the United States.

BACKGROUND: This study examines whether Mexico's controls on ephedrine and pseudoephedrine, the two precursor chemicals that yield the most potent form of methamphetamine, d-methamphetamine, impacted the prevalence/availability of less potent types of methamphetamine in the United States-types associated with the alternative precursor chemical P2P. METHOD: Using ARIMA-intervention time series analysis of monthly drug exhibits (a prevalence/availability indicator) from the System to Retrieve Information from Drug Evidence (STRIDE), we tested whether Mexico's controls, which began in 2005, were associated with growth/decline in d-methamphetamine and growth/decline in P2P-associated, less potent l-methamphetamine, racemic methamphetamine (a 50:50 ratio of d- and l-isomers), and mixed isomer methamphetamine (an unequal ratio of d- and l-isomers). Heroin, cocaine and marijuana exhibits were used for quasi-control (01/2000-04/2011). RESULTS: Mixed-isomer exhibits constituted about 4% of the methamphetamine exhibits before Mexico's controls, then rose sharply in association with them and remained elevated, constituting about 37% of methamphetamine exhibits in 2010. d-Methamphetamine exhibits dropped sharply; l-methamphetamine and racemic methamphetamine exhibits had small rises. d-Methamphetamine exhibits partially recovered in the US West, but little recovery occurred in the US Central/South. Quasi-control series were generally unaffected. CONCLUSION: The US methamphetamine market changed. Widespread emergence of less potent methamphetamine occurred in conjunction with Mexico's controls. And prevalence/availability of the most potent type of the drug, d-methamphetamine, declined, a partial recovery in the West notwithstanding. Granting that lower potency drugs typically engender less dependence and attendant problems, these findings suggest that, following Mexico's controls, the potential harm of a sizeable amount of the US methamphetamine supply decreased.

Changing over-the-counter ephedrine and pseudoephedrine products to prescription only: impacts on methamphetamine clandestine laboratory seizures.

BACKGROUND: Clandestine laboratory operators commonly extract ephedrine and pseudoephedrine-precursor chemicals used to synthesize methamphetamine-from over-the-counter cold/allergy/sinus products. To prevent this activity, two states, Oregon in 07/2006 and Mississippi in 07/2010, implemented regulations classifying ephedrine and pseudoephedrine as Schedule III substances, making products containing them available by prescription only. Using simple pre-regulation versus post-regulation comparisons, reports claim that the regulations have substantially reduced clandestine laboratory seizures (an indicator of laboratory prevalence) in both states, motivating efforts to implement similar regulation nationally. This study uses ARIMA-intervention time-series analysis to more rigorously evaluate the regulations' impacts on laboratory seizures. METHODS: Monthly counts of methamphetamine clandestine laboratory seizures were extracted from the Clandestine Laboratory Seizure System (2000-early 2011) for Oregon, Mississippi and selected nearby states (for quasi-control). FINDINGS: Seizures in Oregon and nearby western states largely bottomed out months before Oregon's regulation, and changed little thereafter. No significant impact for Oregon's regulation was found. Mississippi and nearby states generally had elevated seizures before Mississippi's regulation. Mississippi experienced a regulation-associated drop of 28.9 seizures (50.2%) in the series level (p<0.01), while nearby states exhibited no comparable decline. CONCLUSIONS: Oregon's regulation encountered a floor effect, making any sizable impact infeasible. Mississippi, however, realized a substantial impact, suggesting that laboratories, if sufficiently extant, can be meaningfully impacted by prescription precursor regulation. It follows that national prescription precursor regulation would have little impact in western states with low indicated laboratory prevalence, but may be of significant use in regions facing higher indicated prevalence.

Mexico's methamphetamine precursor chemical interventions: impacts on drug treatment admissions.

AIMS: To help counter problems related to methamphetamine, Mexico has implemented interventions targeting pseudoephedrine and ephedrine, the precursor chemicals commonly used in the drug's synthesis. This study examines whether the interventions impacted methamphetamine treatment admissions-an indicator of methamphetamine consequences. DESIGN: Quasi-experiment: autoregressive integrated moving average (ARIMA)-based intervention time-series analysis. INTERVENTIONS: precursor chemical restrictions implemented beginning November 2005; major rogue precursor chemical company closed (including possibly the largest single drug-cash seizure in history) March 2007; precursor chemicals banned from Mexico (North America's first precursor ban) August 2008. SETTINGS: Mexico and Texas (1996-2008). MEASUREMENTS: Monthly treatment admissions for methamphetamine (intervention series) and cocaine, heroin and alcohol (quasi-control series). FINDINGS: The precursor restriction was associated with temporary methamphetamine admissions decreases of 12% in Mexico and 11% in Texas. The company closure was associated with decreases of 56% in Mexico and 48% in Texas; these decreases generally remained to the end of the study period. Neither intervention was associated with significant changes in the Mexico or Texas quasi-control series. The analysis of Mexico's ban was indeterminate due largely to a short post-ban series. CONCLUSIONS: This study, one of the first quasi-experimental analyses of an illicit-drug policy in Mexico, indicates that the country's precursor interventions were associated with positive impacts domestically and in one of the Unites States' most populous states--Texas. These interventions, coupled with previous US and Canadian interventions, amount to a new, relatively cohesive level of methamphetamine precursor control across North America's largest nations, raising the possibility that the impacts found here could continue for an extended period.

Proximity to the US-Mexico border: a key to explaining geographic variation in US methamphetamine, cocaine and heroin purity.

AIMS: Although illicit drug purity is a widely discussed health risk, research explaining its geographic variation within a country is rare. This study examines whether proximity to the US-Mexico border, the United States' primary drug import portal, is associated with geographic variation in US methamphetamine, heroin and cocaine purity. DESIGN: Distances (proximity) between the US-Mexico border and locations of methamphetamine, cocaine and heroin seizures/acquisitions (n = 239,070) recorded in STRIDE (System to Retrieve Information from Drug Evidence) were calculated for the period of 1990-2004. The association of drug purity with these distances and other variables, including time and seizure/acquisition size, was examined using hierarchical multivariate linear modeling (HMLM). SETTING: Coterminous United States. FINDINGS: Methamphetamine, cocaine and heroin purity generally decreased with distance from the US-Mexico border. Heroin purity, however, after initially declining with distance, turned upwards-a U-shaped association. During 2000-04, methamphetamine purity also had a U-shaped association with distance. For each of the three drugs, temporal changes in the purity of small acquisitions (<10 g) were typically more dynamic in areas closer to the US-Mexico border. CONCLUSIONS: Geographic variance in methamphetamine, cocaine and heroin purity throughout the coterminous United States was associated with US-Mexico border proximity. The U-shaped associations between border-distance and purity for heroin and methamphetamine may be due to imports of those drugs via the eastern United States and southeast Canada, respectively. That said, areas closer to the US-Mexico border generally had relatively high illicit drug purity, as well as more dynamic change in the purity of small ('retail level') drug amounts.

Impact of Canadian federal methamphetamine precursor and essential chemical regulations on methamphetamine-related acute-care hospital admissions.

BACKGROUND: In response to its domestic methamphetamine problems and an emerging international consensus that methamphetamine precursor and essential chemicals should be controlled, Canada regulated its import/export of ephedrine and pseudoephedrine (precursor chemicals) in January 2003, its domestic distribution of those chemicals in July 2003, and its import/export and manufacturing of essential chemicals (e.g., toluene) in January 2004. This study examines the regulations' impact on the problem of methamphetamine-related hospital admissions in Canada. METHODS: ARIMA-based intervention time-series analysis was used to assess impacts on monthly counts of Canada's methamphetamine-related acute-care hospital admissions (04/1996 to 03/2005). Cocaine-, heroin/opioid-, and alcohol-related hospital admissions were examined as quasi-control time-series. RESULTS: No impact was found for the January 2003 regulation. The July 2003 and January 2004 regulations were associated with 20% and 21% increases, respectively, in methamphetamine-related admissions. No impacts on the quasi-control time-series were found. CONCLUSIONS: This study indicates that Canada's regulations were not associated with reductions in methamphetamine-related hospital admissions. The January 2003 regulation's focus on imports/exports rather than domestic distribution may help explain its lack of impact. In contrast, the two other regulations had salient domestic foci--domestic precursor sales (July 2003) and domestic essential chemical manufacturing (January 2004). Both regulations, however, were associated with increases in admissions, rather than declines. Government reports indicate that a shift in methamphetamine production, from smaller-scale operators to more sophisticated crime organizations (groups better able to circumvent the regulations), occurred around the times of the regulations. Such a shift could increase supply and possibly admissions.

Impact of US and Canadian precursor regulation on methamphetamine purity in the United States.

AIMS: Reducing drug purity is a major, but largely unstudied, goal of drug suppression. This study examines whether US methamphetamine purity was impacted by the suppression policy of US and Canadian precursor chemical regulation. DESIGN: Autoregressive integrated moving average (ARIMA)-intervention time-series analysis. SETTING: Continental United States and Hawaii (1985-May 2005). Interventions US federal regulations targeting precursors, ephedrine and pseudoephedrine, in forms used by large-scale producers were implemented in November 1989, August 1995 and October 1997. US regulations targeting precursors in forms used by small-scale producers (e.g. over-the-counter medications) were implemented in October 1996 and October 2001. Canada implemented federal precursor regulations in January 2003 and July 2003 and an essential chemical (e.g. acetone) regulation in January 2004. MEASUREMENTS: Monthly median methamphetamine purity series. FINDINGS: US regulations targeting large-scale producers were associated with purity declines of 16-67 points; those targeting small-scale producers had little or no impact. Canada's precursor regulations were associated with purity increases of 13-15 points, while its essential chemical regulation was associated with a 13-point decrease. Hawaii's purity was consistently high, and appeared to vary little with the 1990s/2000s regulations. CONCLUSIONS: US precursor regulations targeting large-scale producers were associated with substantial decreases in continental US methamphetamine purity, while regulations targeting over-the-counter medications had little or no impact. Canada's essential chemical regulation was also associated with a decrease in continental US purity. However, Canada's precursor regulations were associated with purity increases: these regulations may have impacted primarily producers of lower-quality methamphetamine, leaving higher-purity methamphetamine on the market by default. Hawaii's well-known preference for 'ice' (high-purity methamphetamine) may have helped to constrain purity there to a high, attenuated range, possibly limiting its sensitivity to precursor regulation.

Methamphetamine suppression and route of administration: precursor regulation impacts on snorting, smoking, swallowing and injecting.

AIMS: The route of drug administration affects risk for dependence and medical harm. This study examines whether routes used by methamphetamine treatment participants were impacted by a major drug suppression policy-federal regulation of the methamphetamine precursor chemicals ephedrine and pseudoephedrine. DESIGN: Autoregressive-integrated moving average (ARIMA) intervention time-series analysis. SETTING: California (1992-2004). INTERVENTIONS: Ephedrine single-ingredient products regulation, implemented August 1995; ephedrine with other active medicinal ingredients regulation, implemented October 1996; pseudoephedrine products regulation, implemented October 1997. MEASUREMENTS: Monthly counts of non-coerced methamphetamine treatment admissions reporting snorting, smoking, swallowing or injecting. Findings After rising sharply, snorting, smoking, swallowing and injecting admissions dropped 50%, 43%, 26% and 26%, respectively, when the 1995 regulation was implemented. Snorting also dropped 38% at the time of the 1997 regulation. Snorting, swallowing and injecting remained at lower levels to the end of the study period. Smoking resurged (40%) at the time of the 1996 regulation and continued rising. CONCLUSIONS: Precursor regulation was associated with changes in the administration of methamphetamine. Injecting, the route with the greatest health risk, entered a long-term reduction. So, too, did snorting and swallowing, two routes with lower risk for dependence. In contrast, smoking, which has a relatively high risk for dependence, dropped, then rebounded and entered a long-term rise. A possible explanation is that injecting, snorting and swallowing were largely linked with US domestic methamphetamine production, which has yet to recover from the regulations. While Mexican production, which was impacted only temporarily by the regulations and has supplanted domestic production, may have helped to diffuse smoking, a route with which it is historically correlated.

Impact of methamphetamine precursor chemical legislation, a suppression policy, on the demand for drug treatment.

Research is needed to help treatment programs plan for the impacts of drug suppression efforts. Studies to date indicate that heroin suppression may increase treatment demand. This study examines whether treatment demand was impacted by a major US methamphetamine suppression policy -- legislation regulating precursor chemicals. The precursors ephedrine and pseudoephedrine, in forms used by large-scale methamphetamine producers, were regulated in August 1995 and October 1997, respectively. ARIMA-intervention time-series analysis was used to examine the impact of each precursor's regulation on monthly voluntary methamphetamine treatment admissions (a measure of treatment demand), including first-time admissions and re-admissions, in California (1992-2004). Cocaine, heroin, and alcohol treatment admissions were used as quasi-control series. The 1995 regulation of ephedrine was found to be associated with a significant reduction in methamphetamine treatment admissions that lasted approximately 2 years. The 1997 regulation of pseudoephedrine was associated with a significant reduction that lasted approximately 4 years. First-time admissions declined more than re-admissions. Cocaine, heroin, and alcohol admissions were generally unaffected. While heroin suppression may be associated with increased treatment demand as suggested by research to date, this study indicates that methamphetamine precursor regulation was associated with decreases in treatment demand. A possible explanation is that, during times of suppression, heroin users may seek treatment to obtain substitute drugs (e.g., methadone), while methamphetamine users have no comparable incentive. Methamphetamine suppression may particularly impact treatment demand among newer users, as indicated by larger declines in first-time admissions.

Impacts of federal precursor chemical regulations on methamphetamine arrests.

AIMS: The US government regulated precursor chemicals, ephedrine and pseudoephedrine, multiple times to limit methamphetamine production/availability and thus methamphetamine problems. Research has found that the regulations reduced methamphetamine hospital admissions, but authors have argued that other problems were unaffected. This study examines whether the regulations impacted methamphetamine arrests. DESIGN: ARIMA-intervention time-series analysis with control series. SETTING: California (1982-2001). MEASUREMENTS: Dependent variable series: monthly methamphetamine arrests. Control series: monthly marijuana arrests and cocaine/heroin arrests. INTERVENTIONS: Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. Pseudoephedrine products: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines)-used mainly by small-scale producers: regulated October 1996. FINDINGS: The regulation targeting small-scale producers (1996) had no significant impact. In contrast, methamphetamine arrests stopped rising and dropped 31% to 45% each of the three times precursor chemicals used by large-scale producers were regulated. Within 3 years of the bulk powder regulation (1989) and again within 2 years of the ephedrine single ingredient regulation (1995), arrests fully rebounded. During the 4 years following the last regulation (pseudoephedrine products, 1997) arrests only partially rebounded. These effects parallel those reported on hospital admissions. The control series were generally unaffected. CONCLUSIONS: Precursor regulations targeting large-scale producers impacted methamphetamine arrests, a criminal justice problem, much as they impacted the public health problem of methamphetamine hospital admissions. Ongoing research is needed to determine whether these problems eventually fully rebound from the last regulation.

Impacts of federal ephedrine and pseudoephedrine regulations on methamphetamine-related hospital admissions.

AIMS: To determine whether the federal regulation of ephedrine and pseudoephedrine, precursors used in illicit methamphetamine production, reduced methamphetamine-related acute care hospital admissions. DESIGN: ARIMA-intervention time-series analysis. SETTING: California (1983-2000), Arizona and Nevada (1991-2000), USA. MEASUREMENTS: Monthly counts of methamphetamine-related acute care hospital admissions. INTERVENTIONS: Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. Products containing pseudoephedrine: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines), used mainly by small-scale producers: regulated October 1996. FINDINGS: In California, the bulk powder regulation stopped a 7-year rise in admissions (1983-89) and reduced them by 35% (P < 0.01). The single ingredient ephedrine regulation stopped a 4-year rise (1992-95) in California, Arizona and Nevada, with 48% (P < 0.01), 71% (P < 0.01) and 52% (P < 0.01) reductions, respectively. The pseudoephedrine products regulation stopped a 2-year rise (1996-97) in California, Arizona and Nevada, with 38% (P < 0.01), 41% (P < 0.05) and 61% (P < 0.01) reductions, respectively. Admissions rose at the end of the study period but were still well below peak 1990s levels. The regulation of ephedrine combined with other active medicinal ingredients had no significant impact in any of the three states. CONCLUSIONS: Regulations targeting precursors used by large-scale producers reduced admissions substantially during the study period. However, the regulation of precursors used primarily by small-scale producers had little, if any, effect.