- Email: [email protected]
Twin epidemics: The surging rise of methamphetamine use in chronic opioid users
Drug and Alcohol Dependence 193 (2018) 14–20
Contents lists available at ScienceDirect
Drug and Alcohol Dependence journal homepage: www.elsevier.com/locate/drugalcdep
Full length article
Twin epidemics: The surging rise of methamphetamine use in chronic opioid users
T
⁎
Matthew S. Ellis , Zachary A. Kasper, Theodore J. Cicero Washington University, Department of Psychiatry, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO 63110 USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Methamphetamine Opioids Polysubstance use
Background/aims: Recent supply-side efforts enacted to curb the opioid epidemic have had both positive (i.e., prescription opioid abuse is on the decline) and negative outcomes (i.e., shifts to other drugs). Given methamphetamine is notably increasing in use across the United States, we sought to understand whether use of methamphetamine has increased among opioid users and whether there is an association between these two epidemics. Methods: Patients (N = 13,521) entering drug treatment programs across the United States completed an anonymous survey of drug use patterns from 2011 to 2017. A subset of these patients (N = 300) was also interviewed to add context and expand on the structured survey. Results: Past month use of methamphetamine significantly increased among treatment-seeking opioid users (+82.6%, p < .001), from 18.8% in 2011 to 34.2% in 2017. The Western region had the greatest increase in past month methamphetamine use (+202.4%, p < 0.001) and the highest prevalence rate in 2017 (63.0%). Significant increases (p < .001) in methamphetamine use were seen among males (+81.8%), females (+97.8%), whites (+100.6%), urban residents (+123.0%) and rural residents (+93.7%). Conclusions: Our studies show that there has been a marked increase in the past month use of methamphetamine in individuals with a primary indication of opioid use disorder. Qualitative data indicated that methamphetamine served as an opioid substitute, provided a synergistic high, and balanced out the effects of opioids so one could function “normally”. Our data suggest that, at least to some extent, efforts limiting access to prescription opioids may be associated with an increase in the use of methamphetamine.
1. Introduction The United States is currently in the midst of an opioid epidemic initiated by the proliferation of opioid prescriptions, starting in the late 1990s, and the subsequent diversion and abuse of these drugs (Guy et al., 2017; International Narcotics Control Board, 2009; Maxwell, 2011; McHugh et al., 2015; Wilkerson et al., 2016). Recently, prevention and intervention efforts have been enacted to curb the supply of these analgesics, including prescription monitoring programs (Brady et al., 2014), legislation limiting the reach of rogue physicians and pill mills (Soelberg et al., 2017), physician education programs (Alford, 2016), and the development of abuse-deterrent formulations (ADF) which are designed to make the inhalation or injection of prescription opioids more difficult (Cicero and Ellis, 2015). While recent downward trends in prescription opioid abuse suggest that these efforts may be having a significant impact (Dart et al., 2015a, b), there have also been unanticipated effects of these prescription-centered, supply-side
⁎
interventions. Studies have shown that treatment-seeking prescription opioid users, faced with a shortage of preferred prescription opioids, shifted to less tamper-resistant prescription opioids, or more ominously, to the far cheaper and more accessible heroin (Cicero et al., 2014; Cicero and Ellis, 2015; Compton et al., 2016). Indeed, while prescription opioid abuse has been noted to be decreasing, overdoses involving opioids, particularly heroin and illicit fentanyl, continues to increase, with over 60,000 deaths in 2016 alone (O’Donnell et al., 2017). While shifts in opioid use patterns as a function of supply reduction efforts have been noted, there is very little data on how these interventions have affected the use of non-opioid psychotomimetic substances. Since polysubstance use is well-established among drug users, it is reasonable to postulate that increases in the use of non-opioids, particularly those easily accessible, may occur as a result of decreasing accessibility of preferred opioid drugs. Furthermore, given that co-ingestion or co-occurring use of opioids and a number of other substances has the potential to increase the risk for a number of adverse health
Corresponding author. E-mail address: [email protected] (M.S. Ellis).
https://doi.org/10.1016/j.drugalcdep.2018.08.029 Received 1 June 2018; Received in revised form 17 August 2018; Accepted 18 August 2018 Available online 10 October 2018 0376-8716/ © 2018 Elsevier B.V. All rights reserved.
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Wal-Mart gift card and a self-addressed stamped envelope which, after completion, was used by the respondent to mail the survey (identified by a unique case number) directly to Washington University in St. Louis (WUSTL). All protocols were approved by the WUSTL Institutional Review Board.
outcomes, particularly overdose fatalities (DuPont, 2018), focusing on changes in the wide spectrum of drugs of abuse seems to be a timely and important research topic. However, most opioid research minimizes the role of polysubstance use, or if it is noted, it is most often as a pointprevalence statistic, with little data on how or why use has changed over time. In particular, there have been media reports that the use of methamphetamine is surging across the country and developing into its own epidemic (Montemayor, 2018; Robles, 2018). Seemingly supporting these anecdotal reports, the Centers for Disease Control and Prevention has noted significant increases in overdose deaths for psychostimulants (i.e., methamphetamine) (Seth et al., 2018), seizures of methamphetamine by U.S. Customs and Border Protection has tripled since 2012 (U.S. Customs and Border Protection, 2018), treatment admissions for methamphetamine has been increasing since 2011 (U.S. Department of Justice, 2017), and the Drug Enforcement Agency has noted that methamphetamine’s purity averages above 90 percent while remaining low-cost (U.S. Department of Justice, 2017). However, according to the 2014 National Survey of Drug Use and Health report, methamphetamine use has remained stable from 2002 to 2014 across all age groups, and more recent data (2015–2016) indicates this trend to be holding steady among the general population (Center for Behavioral Health Statistics and Quality, 2015; National Institute on Drug Abuse, 2018). This suggests that reported increases may be isolated, or may not be captured until further into the future. In either case, little is understood about the relationship, if one exists, between the opioid epidemic and its associated interventions, and methamphetamine-associated outcomes. The purpose of this study was to determine whether there have been significant increases over time in the use of methamphetamine in treatment-seeking opioid users, and to understand the relationship between methamphetamine and opioid use. Such information would be of critical importance for those involved in substance use prevention, intervention and health outcomes management. A two-step strategy was developed to investigate co-occurring methamphetamine and opioid use utilizing data sources from the post-marketing opioid surveillance system, the Researched Abuse Diversion and Addiction Related Surveillance (RADARS®) System: first, to retrospectively identify any significant increases in non-opioid psychotomimetic use in a robust sample (N = 13,521) of individuals entering drug treatment programs for opioid use disorder; and second, using a subset of this sample (N = 300) to prospectively gather both quantitative and qualitative data on motivations and patterns related to any observed increases.
2.2. RAPID sample The Researchers and Participants Interacting Directly (RAPID) Program consists of a subset of participants from the ongoing nationwide Survey of Key Informants’ Patients (SKIP) Program (Study 1) who indicated by a mail-in postcard provided with the SKIP survey that they were willing to give up their anonymity and, following completion of a registration that included written consent, participate in the RAPID Program. RAPID participants complete online surveys (hosted by SurveyMonkey®) with both direct, quantitative questions based on SKIP analyses and prior literature on the topic, as well as open-ended, qualitative essay-style questions in order to explain, in greater detail, responses to quantitative questions. Data for this study were collected from a RAPID survey that ran from April to May 2017 that asked a series of questions on methamphetamine and opioid use patterns and motivations. Participants in the RAPID program were compensated with a $20 Wal-Mart gift card. All protocols were approved by the WUSTL Institutional Review Board (IRB). 3. Data analysis 3.1. Temporal changes in past month use of methamphetamine SKIP respondents (N = 13,521) were asked to identify all substances – tobacco, alcohol (more than 4 times in one day), marijuana, MDMA (ecstasy), cocaine or crack, methamphetamine, prescription stimulants, hallucinogens, anti-anxiety medications, prescription sleep medications, muscle relaxants and anti-depressants – used in the past month for “recreational use, to get high or for any other non-medical reason.” The data for methamphetamine was analyzed yearly from 2011 (2q-4q) to 2017 (1q only). To determine significant changes over time, a bivariate logistic regression was used with the endorsement of methamphetamine (1/0) as the response variable and the year of endorsement as the predictor variable, with the significance level set at 0.01 to account for the large sample size. Data are reported with the percent change from 2011 to 2017 with the associated odds ratios and p-value. Endorsements of past month methamphetamine use were then analyzed as a function of several demographic variables – gender (male/female), race (white/non-white), self-reported urbanicity of residence (urban, suburban, rural) and regionality (Census Bureau-defined Northeast, South, Midwest And West, extrapolated by participant’s 3-digit zip code). In addition, we analyzed past month methamphetamine use alongside the type of opioid(s) used in the past month: prescription opioid(s) only, prescription opioid(s) and heroin, and heroin only. To determine significant changes over time, a bivariate logistic regression was used with the endorsement of a drug (1/0) as the response variable and the year of endorsement as the predictor variable within each specific demographic population, with the significance level set at 0.01 to account for yearly sample size. Data are reported with the percent change from 2011 to 2017 with the associated odds ratios and p-value.
2. Study samples 2.1. SKIP sample This report utilized data from the ongoing nationwide Survey of Key Informants’ Patients (SKIP) Program, a key element of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System, a mosaic of programs that collect and analyze post-marketing data on the abuse and diversion of prescription opioid analgesics and heroin (Dart et al., 2015a, b; Cicero et al., 2007). The SKIP Program consists of a Key Informant network (mean of 172 participating public and private treatment centers per year from 2011 to 2017; range 154–198), with a reasonable representativeness of the four census areas (Region [SKIP %, 2014 Census%]; Midwest [27.9%,21.2%], Northeast [15.5%,17.6%], South [33.6%,37.6%] and West [23.0%,23.6%]). Key Informants were asked to recruit clients (eighteen years and older) who were newly entering their substance abuse treatment program (in order to minimize the potential for repeat surveys) with a primary diagnosis of opioid use disorder, as defined by DSM-IV or V criteria, depending on the time of completion. Clients were asked to complete an anonymous paper survey centered on opioid abuse patterns and related behaviors, with an 85% response rate attained. The survey packet included a $20
3.2. Understanding increases and motivations for opioid + methamphetamine use To explore the patterns and reasons underlying the large increase in methamphetamine use, we gathered both quantitative and qualitative data from a sub-sample of the SKIP study population that participated in an internet-based follow-up survey known as the Researchers and 15
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
4. Results
Supplementary Table 1 contains the detailed annual prevalence rates along with outcomes from the logistic regression analyses. As can be seen in Fig. 2, there were statistically significant positive increases in past month methamphetamine use across all but one demographic category: suburban residents (p = 0.728). As can be seen, the Western region had not only the greatest increase in past month methamphetamine use (+202.4%, p < 0.001), but by far the highest prevalence rate in 2017 so far (63.0%). Aside from the regional differences, use among both males and females nearly doubled, with females having a slightly higher increase (+97.8%, p < 0.001) and prevalence rate in 2017 (39.1%) than males (+81.8% and 31.9%, respectively). Whites had nearly a four-fold increase in methamphetamine use over nonwhites (+100.6%, p < 0.001 vs. + 28.0%, p < 0.002), and while urban residents showed the greatest increase over time (+123.0%, p < 0.001), 2017 prevalence rates were higher in rural areas (34.9% vs. 45.7%, respectively). In terms of age, the greatest increase was among 35–44-year old’s (+120.5%, p < 0.001), with a near equal prevalence rate in 2017 among 18–24 (34.3%), 25–34 (38.8%) and 35–44 (35.6%) year old’s. In terms of opioid user groups, while the greatest user increase was among those who only used heroin (+358.6%, p < 0.001) in the past month, this rate in 2017 was similar to that of those who used prescription opioids only (24.1% vs. 29.3%, respectively) and less than those who used both prescription opioids and heroin (41.5%).
4.1. Temporal changes in past month use of methamphetamine
4.2. Characteristics of SKIP and RAPID samples
Past month use of methamphetamine had the largest increase among treatment-seeking opioid users (+82.6%, p < .001), from 18.8% of respondents reporting past month use in 2011 compared to 34.2% in 2017. Compared to other substances surveyed, increases only occurred for three other substances and to a much smaller degree than that of methamphetamine: prescription stimulants (+14.6%), marijuana (+5.8%) and tobacco (+4.5%). Fig. 1 shows that the increase in the prevalence of past month methamphetamine use was a fairly steady trend when presented by year from 2011 to 2017. Fig. 2 shows the past month use of methamphetamine from 2011 to 2017 stratified by gender, ethnicity, urbanicity, and regionality.
As indicated in Table 1, both SKIP and RAPID samples had nearly equal proportions of males and females (47.7% vs. 54.7%, respectively), although it should be noted the RAPID sample, compared to the SKIP sample, had a lower proportion of non-whites (9.4% vs. 20.3%) and younger participants (4.4% under 25, vs. 21.1%)
Participants Interacting Directly (RAPID) Program to gather both qualitative and quantitative data. Data were analyzed for 300 RAPID participants who completed an online survey from April to May 2017 on patterns and motivations of co-occurring methamphetamine and opioid use, along with their views as experienced substance users on motivations and patterns of methamphetamine use in their localized areas. Descriptive statistics were calculated for discrete variables. Open-ended responses to two questions, “Why did you use methamphetamine AND opioids (prescription opioids OR heroin)?” and, for those who indicated they had observed increases in methamphetamine, “In your opinion, WHY has methamphetamine use increased recently among opioid users in your area?”, were entered into NVivo 10 and coded using a descriptive coding scheme. Two independent researchers participated in the coding process, which included establishing codes and meanings and cross-checking code choices. Regular discussions were held between the coders that yielded insights to refine the coding scheme and facilitate agreement on code choices. Finally, the final set of codes and their meanings were transformed into longer and more descriptive themes. The primary themes and representative quotes are included below, verbatim; the total numbers of corresponding responses are shown in parentheses. Quantitative data were analyzed using IBM SPSS Statistics v24.
4.3. Motivations for opioid + methamphetamine use Among RAPID participants, 65.0% (n = 195/300) had a lifetime history of methamphetamine use, with 76.4% of these (N = 149/195) indicating they used methamphetamine in the same time period they
Fig. 1. The percent of SKIP respondents (N = 13,521) who endorsed past month use of methamphetamine by year from 2011, quarters 2–4, to 2017, quarter 1. 16
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Fig. 2. The percent of SKIP respondents who endorsed past month use of methamphetamine by year from 2011 to 2017 by A) gender, B) race, C) urbanicity, and D) region.
energy provided by methamphetamine offset the sedation provided by opioids so that they could function and be productive, or that opioids were used to come down (e.g., sleep) from the stimulation produced by methamphetamine. It was also noted by 15.2% that if opioids were not available, then methamphetamine was used as a substitute, often as a way of managing withdrawal symptoms.
Table 1 Demographics of SKIP and RAPID samples. Group
Variable
SKIP (n = 13,521)
RAPID (n = 300)
Gender
Male Female White Nonwhite 18-24 25-34 35-44 45+
52.3% 47.7% 79.7% 20.3% 21.1% 42.7% 20.6% 15.6%
45.3% 54.7% 90.6% 9.4% 4.3% 37.5% 35.1% 23.1%
Ethnicity Age
4.4. Understanding increases in methamphetamine use We also asked RAPID participants who responded ‘Yes’ to being knowledgeable about the current drug culture/market in their area (N = 97) whether methamphetamine use had increased in recent years among opioid users in their area. Over three-fourths of the sample (76.3%, n = 74/97) indicated use had increased, and we asked them to elaborate, in their own words, the reasons behind such increases. Table 3 shows that the most common responses (N = 72; 2 provided no response) were that methamphetamine was easily accessible (38.9%) and/or cheap (30.6%), in part because it was noted to be inexpensive to make at home. Interestingly, several participants noted that it was becoming easier to find than opioids due to “restrictions” on opioids and, hence, it was used to provide some form of sought-after euphoria produced by either opioids or methamphetamine. The second most common response was that people were purposively seeking out the high of methamphetamine and opioids together because co-occurring use had become popular (37.5%) among social groups as a means of balancing the highs and lows of these two dichotomous drugs so that they could function more effectively.
were using opioids. When this latter group was asked to define their typical pattern of co-occurring methamphetamine and opioid use, the vast majority (79.9%, n = 119/149) used both substances on the same day, either ‘at the same time’ (38.9%); ‘immediately before or immediately after’ one another (9.4%); or on the ‘same day, but at different times’ (31.5%). To determine the frequency of use, RAPID participants were asked how many days in an average month they used methamphetamine while they were using opioids. The mean number of days of co-occurring use was 14.6 days per month ( ± 11.2 SD). Table 2 outlines the qualitative themes provided when participants (N = 145; 4 provided no response) were asked to describe their motivations for using both methamphetamines and opioids. While the most frequent motivator (51.0%) was the high produced by co-occurring use (i.e., a roller coaster or synergistic high), the balance these two drugs offered one another played an important role for over a third of the sample (38.6%). For example, most of these individuals noted the 17
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Table 2 Motivations for co-occuring use of methamphetamine and opioids (N = 145). Coded responses
N (%)
Representative quotes
High-seeking
74 (51.0)
Balance of effect
56 (38.6)
(1) (2) (3) (1) (2)
Availabile as Opioid Substitute
22 (15.2)
Escape from life/ Numbness
14 (9.7)
Addiction
13 (9.0)
Social Setting
9 (6.2)
(3) (4) (1) (2) (3) (1) (2) (3) (1) (2) (1) (2)
The high was like a roller coaster I enjoyed the synergetic effect I was told that it was a fabulous high, so I tried it and loved it I could function on them together I used meth to give me the rush & to have energy. I used heroin to numb myself or to get the high from the opioids. If i used too much meth id use heroin to calm down; Cause I was trying to get allot of work done energy with no pain make you be able to get stuff done Use meth sometimes to counter the drowsiness from opiods So when i couldn't use opioids because of money or availability, i used methamphetamine I would use meth when I had ran out. When I was really sick from the withdrawal and I couldn't find opioids, I would use methamphetamine Just feel numb n not worry about my problems Because I hated to be fully aware and have to percieve my surroundings, situations and life. When I was high it was like walking around in a dream state. I was numbed Escape from the reality of life Because I'm a drug addict and would do anything I could to avoid being sober. I would use any excuse I could to justify use of different drugs Because I'm a addict and it didn't matter how I got high just that I did. Initially it was just to party with socially then became addicted and had to use daily The pupil dilation and other signs that would make it obvious that I was high would be less noticable as well. Made it a lot easily to hide from people around me.
5. Discussion
elsewhere, the effects provide some relief from certain life stressors (Cicero et al., 2017; Lipari et al., 2017). Finally, more than a few participants noted that methamphetamine helped alleviate opioid withdrawal symptoms, most likely because of their dual action on dopamine reward systems in the brain (Mori et al., 2016). The precise mechanisms involved in this seemingly paradoxical effect – an excitatory drug being used to treat an opioid withdrawal syndrome which by its nature is also excitatory needs to be further examined. What is unclear from our research is why the sudden growth in the use of methamphetamine given that co-occurring use of stimulants and opioids has been noted for years (e.g., speedballs)? The most plausible explanation, as noted by many participants, is that methamphetamine is now freely available at low cost, with participants noting increases in homemade methamphetamine, contrary to media reports that this method has been replaced with Mexican methamphetamine, and accessibility to it through their opioid sources (i.e., dealers). While homemade methamphetamine was noted, some of this increase in accessibility is still likely due to the fact that Mexican drug cartels recognized a market and became a ready resource for the synthesized drug, often known as “ice” or crystal meth. Thus, inexpensive (relatively) drugs from Mexico have not only decreased the dangerous process of self-made meth but provided high-grade drugs at a very affordable rate (Loza et al., 2016; Meacham et al., 2016; U.S. Department of Justice, 2017). This sourced drug from Mexico likely explains some of the geographical specificity we observed – meth was more prevalent in the west than in the east, although there seems to be some growth in use from west to east. A second possibility to explain the increase in the
These studies indicate that there has been a marked increase in the past month use of methamphetamine in individuals with a primary indication of opioid use disorder. From 2011 to 2017, methamphetamine use nearly doubled from 18.8% in 2011 to 34.2% of all opioid users in 2017 entering a drug treatment program. Of note, among those using both methamphetamine and opioids, such use was not separated but often linked together, with the majority using both drugs within the same day, and even more concerning, doing so for nearly half the days of an average month. What makes these findings of timely importance is that they may help explain the contradiction between media reports of increases in methamphetamine use and a lack of significant change among rates reported by national surveys such as NSDUH (Center for Behavioral Health Statistics and Quality, 2015; National Institute on Drug Abuse, 2018); increases in methamphetamine use may be an issue unique to certain populations such as ours. There are two aspects of this outcome which need to be further addressed: First, what motivated couse; and second, why the steady escalation of methamphetamine uses from 2011 to 2017 and is this likely to continue to increase? With respect to co-use of opioids and methamphetamine, most users indicated that they either liked the synergistic high (i.e., the roller coaster effect) or used the drugs to balance out the effects of each other so that they could function as normally as possible. In addition to this relatively straightforward conclusion, many of our users stated that such use was a function of their addiction, noting that specific drugs were less important than use in general, or as reported here and
Table 3 Participant explanations of increases in methamphetamine use in their local areas (N = 72). Coded responses
N (%)
Representative quotes
Increased Accessibility
28 (38.9)
Increased Popularity
27 (37.5)
Low cost
22 (30.6)
Opioid restrictions
10 (13.9)
Dealer supply
8 (11.1)
(1) (2) (3) (1) (2) (3) (1) (2) (1) (2) (1) (2)
It has increased because it is so easy to make. Because it's home made, easier to get, more around. Meth has become more readily available and is cheaper in the area where I'm from. Many people can make it. Many people enjoy the effects of mixing opioids and meth. Because people are figuring out the effects of prolonging euphoric effects of meth and opiates at the same time. Meth makes it easier to be a fuctioning addict. Affordability and availability. Prices have gone from $200/gram to $80–100/g in recent years Opiods have become so expensive, whereas method can be made at home with fairly inexpensive products bought at the drug store. Opiate manufacturers making it harder to manipulate the drugs to get high, so people are looking for ways to enhance the opiates The stricter laws on opioid prescriptions (3) Due to more restrictions on pharmaceutical opioids Because most dealers sell both When the drugs people want are not readily availible they turn to drugs that are availible & drug dealers selling both kinds of drugs.
18
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Role of funding source
use of meth by those with an opioid use disorder could be related to a shortage in the supply of opioids due to supply reduction efforts, as several participants noted. Opioid users, faced with opioid withdrawal and/or their inability to get high with opioids may turn to the next best thing, so to speak. Thus, the end-point would seem to be to get high, no matter how this was achieved. It should also be noted that although one may posit that methamphetamine use is associated most strongly with heroin use, co-occurring use increased regardless of which opioid was used, a prescription opioid or illicit heroin. Our initial hypothesis which gave rise to these studies was that the supply-reduction efforts for prescription opioids (i.e., abuse-deterrent formulation, prescription monitoring programs, legislation, etc.) might lead to increased use of not only other opioids (e.g., heroin), but nonopioid euphorigenic substances. Although our results do, in fact, show a rapid escalation in methamphetamine use, attributable primarily to increases in accessibility and popularity due to the perceived high, there was some relationship to the lack of availability of opioids. These data suggest that the experience of euphoria may play a role in the selection of other opioid or non-opioid drugs if the preferred drug of choice is less accessible as it was previously. Thus, in the context of polysubstance use, it appears that the so-called “balloon theory” applies to not just to opioids but perhaps the entire use of euphorigenic drugs: decreases in use of opioids may stimulate the use of other drugs of abuse. It needs to be stressed that this remains a hypothesis and there are other possible explanations of our results. Specifically, an increase of supply of methamphetamine and “word of mouth” touting the pleasure experienced by the synergistic high produced by methamphetamines and opioids may be the simplest answer. Clearly, additional studies need to be carried out to more definitively test these competing hypotheses, but it is nevertheless clear that over a third of chronic opioid users have discovered the “benefits” of dual use of methamphetamines and opioids. Such co-occurring use of methamphetamine and opioids highlights the need for more research and understanding of polysubstance use, particularly its role in furthering prevention and treatment efforts that often are siloed into a particular drug of interest. Interventions focusing solely on opioids may not be effective for those who may engage or have already engaged in experimentation with multiple drugs of abuse. For instance, in terms of treatment, the clinical guidelines for buprenorphine indicate that such pharmacotherapy “will not necessarily have a beneficial effect on an individual’s use of other drugs” (Center for Substance Abuse Treatment, 2004). In addition, emerging substance use-related vaccines not only are substance dependent but in the case of opioids, are likely to be ineffective even against more than one class of opioid (Bremer et al., 2017; Kuppili et al., 2018; Olson and Janda, 2018). This study highlights not only the need to consider the demand side of substance use and what drives individuals to use not only one drug, but drugs in general, and how this understanding of polysubstance use, and its related outcomes, can be incorporated into prevention and treatment. There are important limitations to our studies. The SKIP and RAPID programs are retrospectives in nature which could present issues of recall. Also, since ours is a treatment-sourced sample, one could also argue that the results are not representative of those who use opioids or methamphetamine “recreationally” or those who do not seek treatment and thus, generalizability is limited. In addition, the RAPID sample included lower numbers of younger and non-white participants, populations which may demonstrate different patterns of use than what was found. These populations may require extra attention for participation in follow-up studies, which we hope to focus on as our research continues. Finally, more research is needed to validate our findings and further understand these seemingly intertwined epidemics of methamphetamines and opioids, particularly in terms of intervention and treatment delivery.
This work was supported by private funds from Washington University in St. Louis and the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System, an independent nonprofit postmarketing surveillance system that is supported by subscription fees from pharmaceutical manufacturers, who use these data for pharmacovigilance activities and to meet regulatory obligations. RADARS System is the property of Denver Health and Hospital Authority, a political subdivision of the State of Colorado. Denver Health retains exclusive ownership of all data, databases and systems. Subscribers do not participate in data collection nor do they have access to the raw data. Contributors All authors participated in analyzing and interpreting the data, and in drafting and reviewing the manuscript. All authors meet ICMJE criteria for authorship and have approved the final version of the manuscript. Conflict of interest All authors are employees of Washington University in St. Louis, which receives research funding from Denver Health and Hospital Authority. Author Cicero serves as a paid consultant on the Scientific Advisory Board of the Researched Abuse, Diversion and AddictionRelated Surveillance (RADARS®) System. None of the authors have a direct financial, commercial or other relationship with any of the subscribers of the RADARS® System. Acknowledgement None. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.drugalcdep.2018.08. 029. References Alford, D.P., 2016. Opioid prescribing for chronic pain—achieving the right balance through education. N. Engl. J. Med. 374, 301–303. Brady, J.E., Wunsch, H., DiMaggio, C., Lang, B.H., Giglio, J., Li, G., 2014. Prescription drug monitoring and dispensing of prescription opioids. Public Health Rep. 129, 139–147. Bremer, P.T., Schlosburg, J.E., Banks, M.L., Steele, F.F., Zhou, B., Poklis, J.L., Janda, K.D., 2017. Development of a clinically viable heroin vaccine. J. Am. Chem. Soc. 139, 8601–8611. Center for Behavioral Health Statistics and Quality, 2015. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. HHS Publication No. SMA 15-4927, NSDUH Series H-50. Available at. http://www. samhsa.gov/data/. Center for Substance Abuse Treatment, 2004. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration. Available at. https://www.ncbi. nlm.nih.gov/pubmed/22514846. Cicero, T.J., Ellis, M.S., 2015. Abuse-deterrent formulations and the prescription opioid abuse epidemic in the United States: lessons learned from OxyContin. JAMA Psychiatry 72, 424–430. Cicero, T.J., Dart, R.C., Indiardi, J.A., Woody, G.E., Schnoll, S., Munoz, A., 2007. The development of a comprehensive risk-management program for prescription opioid analgesics: Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®). Pain Med. 8, 157–170. Cicero, T.J., Ellis, M.S., Surratt, H.L., Kurtz, S.P., 2014. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry 71, 821–826. Cicero, T.J., Ellis, M.S., Kasper, Z.A., 2017. Understanding the demand side of the prescription opioid epidemic: does the initial source of opioids matter? Drug Alcohol
19
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Mexico. J. Stud. Alcohol Drugs 77, 774–781. Montemayor, S., 2018. In the Shadow of the Opioid Crisis, Meth Has Roared Back into Minnesota. Star Tribune, Minneapolis May 29. http://m.startribune.com/minnesotaopioid-deaths-rise-despite-attention-intervention/424836053/. Mori, T., Iwase, Y., Saeki, T., Iwata, N., Murata, A., Masukawa, D., Suzuki, T., 2016. Differential activation of dopaminergic systems in rat brain basal ganglia by morphine and methamphetamine. Neuroscience 322, 164–170. National Institute on Drug Abuse, 2018. National Survey of Drug Use and Health: Trends in Prevalence of Various Drugs from Ages 12 or Older, Ages 12 to 17, Ages 18 to 25, and Ages 26 or Older; 2015–2016. Available at:. https://www.drugabuse.gov/ national-survey-drug-use-health. O’Donnell, J.K., Halpin, J., Mattson, C.L., Goldberger, B.A., Gladden, R.M., 2017. Deaths involving fentanyl, fentanyl analogs, and U-47700-10 States, July–December 2016. MMWR Morb. Mortal. Wkly. Rep. 66, 1197–1202. Olson, M.E., Janda, K.D., 2018. Vaccines to combat the opioid crisis. Vaccines that prevent opioids and other substances of abuse from entering the brain could effectively treat addiction and abuse. EMBO Rep. 19, 5–9. Robles, F., 2018. Meth, the Forgotten Killer, is Back. And It’s Everywhere. Retrieved from. The New York Times. https://www.nytimes.com/2018/02/13/us/methcrystal-drug.html. Seth, P., Scholl, L., Rudd, R.A., Bacon, S., 2018. Overdose deaths involving opioids, cocaine, and psychostimulants – United States, 2015–2016. MMWR Morb. Mortal. Wkly. Rep. 67, 349–358. Soelberg, C.D., Brown Jr., R.E., Du Vivier, D., Meyer, J.E., Ramachandran, B.K., 2017. The US opioid crisis: current federal and state legal issues. Anesth. Analg. 125, 1675–1681. U.S. Customs and Border Protection, 2018. CBP Enforcement Statistics FY. Accessed at. on May 30, 2018. https://www.cbp.gov/newsroom/stats/cbp-enforcementstatistics. U.S. Department of Justice, Drug Enforcement Administration, 2017. 2017 National Drug Threat Assessment. DEA-DCT-DIR-040-17. Available at:. https://www.dea.gov/ documents/2017/10/01/2017-national-drug-threat-assessment. Wilkerson, R.G., Kim, H.K., Windsor, T.A., Mareiniss, D.P., 2016. The opioid epidemic in the United States. Emerg. Med. Clin. North Am. 34, e1–e23.
Depend. 173, S4–S10. Compton, W.M., Jones, C.M., Baldwin, G.T., 2016. Relationship between nonmedical prescription-opioid use and heroin use. N. Engl. J. Med. 374, 154–163. Dart, R.C., Surratt, H.L., Cicero, T.J., Parrino, M.W., Severtson, S.G., Bucher-Bartelson, B., Green, J.L., 2015a. Trends in opioid analgesic abuse and mortality in the United States. N. Engl. J. Med. 372, 241–248. Dart, R.C., Surratt, H.L., Cicero, T.J., Parrino, M.W., Severtson, S.G., Bucher-Bartelson, B., Green, J.L., 2015b. Supplementary Appendix: trends in opioid analgesic abuse and mortality in the United States. N. Eng. J. Med. 372, 241–248. DuPont, R.L., 2018. The opioid epidemic is an historic opportunity to improve both prevention and treatment. Brain Res. Bull. 138, 112–114. Guy Jr., G.P., Zhang, K., Bohm, M.K., Losby, J., Lewis, B., Young, R., Murphy, L.B., Dowell, D., 2017. Vital signs: changes in opioid prescribing in the United States, 2006–2015. MMWR Morb. Mortal. Wkly. Rep. 66, 697–704. International Narcotics Control Board, 2009. Report of the International Narcotics Control Board for 2008. Available at:. United Nations Publications, New York, NY. https://www.incb.org/incb/en/publications/annual-reports/annual-report-2008. html. Kuppili, P.P., Manohar, H., Menon, V., 2018. Current state of vaccines in psychiatry—a narrative review. Asian J. Psychiatry 31, 112–120. Lipari, R.N., Williams, M., Van Horn, S.L., 2017. Why Do Adults Misuse Prescription Drugs? The CBHSQ Report. Available at:. Substance Abuse and Mental Health Services Administration (US), Rockville (MD). https://www.samhsa.gov/data/sites/ default/files/report_3210/ShortReport-3210.html. Loza, O., Ramos, R., Ferreira-Pinto, J., Hernandez, M.T., Villalobos, S.A., 2016. A qualitative exploration of perceived gender differences in methamphetamine use among women who use methamphetamine on the Mexico-U.S. border. J. Ethn. Subst. Abuse 15, 405–424. Maxwell, J.C., 2011. The prescription drug epidemic in the United States: a perfect storm. Drug Alcohol Rev. 30, 264–270. McHugh, R.K., Nielsen, S., Weiss, R.D., 2015. Prescription drug abuse: from epidemiology to public policy. J. Subst. Abuse Treat. 48, 1–7. Meacham, M.C., Strathdee, S.A., Rangel, G., Armenta, R.F., Gaines, T.L., Garfein, R.S., 2016. Prevalence and correlates of heroin-methamphetamine co-injection among persons who inject drugs in San Diego, California, and Tijuana, Baja California,
20
Contents lists available at ScienceDirect
Drug and Alcohol Dependence journal homepage: www.elsevier.com/locate/drugalcdep
Full length article
Twin epidemics: The surging rise of methamphetamine use in chronic opioid users
T
⁎
Matthew S. Ellis , Zachary A. Kasper, Theodore J. Cicero Washington University, Department of Psychiatry, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO 63110 USA
A R T I C LE I N FO
A B S T R A C T
Keywords: Methamphetamine Opioids Polysubstance use
Background/aims: Recent supply-side efforts enacted to curb the opioid epidemic have had both positive (i.e., prescription opioid abuse is on the decline) and negative outcomes (i.e., shifts to other drugs). Given methamphetamine is notably increasing in use across the United States, we sought to understand whether use of methamphetamine has increased among opioid users and whether there is an association between these two epidemics. Methods: Patients (N = 13,521) entering drug treatment programs across the United States completed an anonymous survey of drug use patterns from 2011 to 2017. A subset of these patients (N = 300) was also interviewed to add context and expand on the structured survey. Results: Past month use of methamphetamine significantly increased among treatment-seeking opioid users (+82.6%, p < .001), from 18.8% in 2011 to 34.2% in 2017. The Western region had the greatest increase in past month methamphetamine use (+202.4%, p < 0.001) and the highest prevalence rate in 2017 (63.0%). Significant increases (p < .001) in methamphetamine use were seen among males (+81.8%), females (+97.8%), whites (+100.6%), urban residents (+123.0%) and rural residents (+93.7%). Conclusions: Our studies show that there has been a marked increase in the past month use of methamphetamine in individuals with a primary indication of opioid use disorder. Qualitative data indicated that methamphetamine served as an opioid substitute, provided a synergistic high, and balanced out the effects of opioids so one could function “normally”. Our data suggest that, at least to some extent, efforts limiting access to prescription opioids may be associated with an increase in the use of methamphetamine.
1. Introduction The United States is currently in the midst of an opioid epidemic initiated by the proliferation of opioid prescriptions, starting in the late 1990s, and the subsequent diversion and abuse of these drugs (Guy et al., 2017; International Narcotics Control Board, 2009; Maxwell, 2011; McHugh et al., 2015; Wilkerson et al., 2016). Recently, prevention and intervention efforts have been enacted to curb the supply of these analgesics, including prescription monitoring programs (Brady et al., 2014), legislation limiting the reach of rogue physicians and pill mills (Soelberg et al., 2017), physician education programs (Alford, 2016), and the development of abuse-deterrent formulations (ADF) which are designed to make the inhalation or injection of prescription opioids more difficult (Cicero and Ellis, 2015). While recent downward trends in prescription opioid abuse suggest that these efforts may be having a significant impact (Dart et al., 2015a, b), there have also been unanticipated effects of these prescription-centered, supply-side
⁎
interventions. Studies have shown that treatment-seeking prescription opioid users, faced with a shortage of preferred prescription opioids, shifted to less tamper-resistant prescription opioids, or more ominously, to the far cheaper and more accessible heroin (Cicero et al., 2014; Cicero and Ellis, 2015; Compton et al., 2016). Indeed, while prescription opioid abuse has been noted to be decreasing, overdoses involving opioids, particularly heroin and illicit fentanyl, continues to increase, with over 60,000 deaths in 2016 alone (O’Donnell et al., 2017). While shifts in opioid use patterns as a function of supply reduction efforts have been noted, there is very little data on how these interventions have affected the use of non-opioid psychotomimetic substances. Since polysubstance use is well-established among drug users, it is reasonable to postulate that increases in the use of non-opioids, particularly those easily accessible, may occur as a result of decreasing accessibility of preferred opioid drugs. Furthermore, given that co-ingestion or co-occurring use of opioids and a number of other substances has the potential to increase the risk for a number of adverse health
Corresponding author. E-mail address: [email protected] (M.S. Ellis).
https://doi.org/10.1016/j.drugalcdep.2018.08.029 Received 1 June 2018; Received in revised form 17 August 2018; Accepted 18 August 2018 Available online 10 October 2018 0376-8716/ © 2018 Elsevier B.V. All rights reserved.
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Wal-Mart gift card and a self-addressed stamped envelope which, after completion, was used by the respondent to mail the survey (identified by a unique case number) directly to Washington University in St. Louis (WUSTL). All protocols were approved by the WUSTL Institutional Review Board.
outcomes, particularly overdose fatalities (DuPont, 2018), focusing on changes in the wide spectrum of drugs of abuse seems to be a timely and important research topic. However, most opioid research minimizes the role of polysubstance use, or if it is noted, it is most often as a pointprevalence statistic, with little data on how or why use has changed over time. In particular, there have been media reports that the use of methamphetamine is surging across the country and developing into its own epidemic (Montemayor, 2018; Robles, 2018). Seemingly supporting these anecdotal reports, the Centers for Disease Control and Prevention has noted significant increases in overdose deaths for psychostimulants (i.e., methamphetamine) (Seth et al., 2018), seizures of methamphetamine by U.S. Customs and Border Protection has tripled since 2012 (U.S. Customs and Border Protection, 2018), treatment admissions for methamphetamine has been increasing since 2011 (U.S. Department of Justice, 2017), and the Drug Enforcement Agency has noted that methamphetamine’s purity averages above 90 percent while remaining low-cost (U.S. Department of Justice, 2017). However, according to the 2014 National Survey of Drug Use and Health report, methamphetamine use has remained stable from 2002 to 2014 across all age groups, and more recent data (2015–2016) indicates this trend to be holding steady among the general population (Center for Behavioral Health Statistics and Quality, 2015; National Institute on Drug Abuse, 2018). This suggests that reported increases may be isolated, or may not be captured until further into the future. In either case, little is understood about the relationship, if one exists, between the opioid epidemic and its associated interventions, and methamphetamine-associated outcomes. The purpose of this study was to determine whether there have been significant increases over time in the use of methamphetamine in treatment-seeking opioid users, and to understand the relationship between methamphetamine and opioid use. Such information would be of critical importance for those involved in substance use prevention, intervention and health outcomes management. A two-step strategy was developed to investigate co-occurring methamphetamine and opioid use utilizing data sources from the post-marketing opioid surveillance system, the Researched Abuse Diversion and Addiction Related Surveillance (RADARS®) System: first, to retrospectively identify any significant increases in non-opioid psychotomimetic use in a robust sample (N = 13,521) of individuals entering drug treatment programs for opioid use disorder; and second, using a subset of this sample (N = 300) to prospectively gather both quantitative and qualitative data on motivations and patterns related to any observed increases.
2.2. RAPID sample The Researchers and Participants Interacting Directly (RAPID) Program consists of a subset of participants from the ongoing nationwide Survey of Key Informants’ Patients (SKIP) Program (Study 1) who indicated by a mail-in postcard provided with the SKIP survey that they were willing to give up their anonymity and, following completion of a registration that included written consent, participate in the RAPID Program. RAPID participants complete online surveys (hosted by SurveyMonkey®) with both direct, quantitative questions based on SKIP analyses and prior literature on the topic, as well as open-ended, qualitative essay-style questions in order to explain, in greater detail, responses to quantitative questions. Data for this study were collected from a RAPID survey that ran from April to May 2017 that asked a series of questions on methamphetamine and opioid use patterns and motivations. Participants in the RAPID program were compensated with a $20 Wal-Mart gift card. All protocols were approved by the WUSTL Institutional Review Board (IRB). 3. Data analysis 3.1. Temporal changes in past month use of methamphetamine SKIP respondents (N = 13,521) were asked to identify all substances – tobacco, alcohol (more than 4 times in one day), marijuana, MDMA (ecstasy), cocaine or crack, methamphetamine, prescription stimulants, hallucinogens, anti-anxiety medications, prescription sleep medications, muscle relaxants and anti-depressants – used in the past month for “recreational use, to get high or for any other non-medical reason.” The data for methamphetamine was analyzed yearly from 2011 (2q-4q) to 2017 (1q only). To determine significant changes over time, a bivariate logistic regression was used with the endorsement of methamphetamine (1/0) as the response variable and the year of endorsement as the predictor variable, with the significance level set at 0.01 to account for the large sample size. Data are reported with the percent change from 2011 to 2017 with the associated odds ratios and p-value. Endorsements of past month methamphetamine use were then analyzed as a function of several demographic variables – gender (male/female), race (white/non-white), self-reported urbanicity of residence (urban, suburban, rural) and regionality (Census Bureau-defined Northeast, South, Midwest And West, extrapolated by participant’s 3-digit zip code). In addition, we analyzed past month methamphetamine use alongside the type of opioid(s) used in the past month: prescription opioid(s) only, prescription opioid(s) and heroin, and heroin only. To determine significant changes over time, a bivariate logistic regression was used with the endorsement of a drug (1/0) as the response variable and the year of endorsement as the predictor variable within each specific demographic population, with the significance level set at 0.01 to account for yearly sample size. Data are reported with the percent change from 2011 to 2017 with the associated odds ratios and p-value.
2. Study samples 2.1. SKIP sample This report utilized data from the ongoing nationwide Survey of Key Informants’ Patients (SKIP) Program, a key element of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System, a mosaic of programs that collect and analyze post-marketing data on the abuse and diversion of prescription opioid analgesics and heroin (Dart et al., 2015a, b; Cicero et al., 2007). The SKIP Program consists of a Key Informant network (mean of 172 participating public and private treatment centers per year from 2011 to 2017; range 154–198), with a reasonable representativeness of the four census areas (Region [SKIP %, 2014 Census%]; Midwest [27.9%,21.2%], Northeast [15.5%,17.6%], South [33.6%,37.6%] and West [23.0%,23.6%]). Key Informants were asked to recruit clients (eighteen years and older) who were newly entering their substance abuse treatment program (in order to minimize the potential for repeat surveys) with a primary diagnosis of opioid use disorder, as defined by DSM-IV or V criteria, depending on the time of completion. Clients were asked to complete an anonymous paper survey centered on opioid abuse patterns and related behaviors, with an 85% response rate attained. The survey packet included a $20
3.2. Understanding increases and motivations for opioid + methamphetamine use To explore the patterns and reasons underlying the large increase in methamphetamine use, we gathered both quantitative and qualitative data from a sub-sample of the SKIP study population that participated in an internet-based follow-up survey known as the Researchers and 15
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
4. Results
Supplementary Table 1 contains the detailed annual prevalence rates along with outcomes from the logistic regression analyses. As can be seen in Fig. 2, there were statistically significant positive increases in past month methamphetamine use across all but one demographic category: suburban residents (p = 0.728). As can be seen, the Western region had not only the greatest increase in past month methamphetamine use (+202.4%, p < 0.001), but by far the highest prevalence rate in 2017 so far (63.0%). Aside from the regional differences, use among both males and females nearly doubled, with females having a slightly higher increase (+97.8%, p < 0.001) and prevalence rate in 2017 (39.1%) than males (+81.8% and 31.9%, respectively). Whites had nearly a four-fold increase in methamphetamine use over nonwhites (+100.6%, p < 0.001 vs. + 28.0%, p < 0.002), and while urban residents showed the greatest increase over time (+123.0%, p < 0.001), 2017 prevalence rates were higher in rural areas (34.9% vs. 45.7%, respectively). In terms of age, the greatest increase was among 35–44-year old’s (+120.5%, p < 0.001), with a near equal prevalence rate in 2017 among 18–24 (34.3%), 25–34 (38.8%) and 35–44 (35.6%) year old’s. In terms of opioid user groups, while the greatest user increase was among those who only used heroin (+358.6%, p < 0.001) in the past month, this rate in 2017 was similar to that of those who used prescription opioids only (24.1% vs. 29.3%, respectively) and less than those who used both prescription opioids and heroin (41.5%).
4.1. Temporal changes in past month use of methamphetamine
4.2. Characteristics of SKIP and RAPID samples
Past month use of methamphetamine had the largest increase among treatment-seeking opioid users (+82.6%, p < .001), from 18.8% of respondents reporting past month use in 2011 compared to 34.2% in 2017. Compared to other substances surveyed, increases only occurred for three other substances and to a much smaller degree than that of methamphetamine: prescription stimulants (+14.6%), marijuana (+5.8%) and tobacco (+4.5%). Fig. 1 shows that the increase in the prevalence of past month methamphetamine use was a fairly steady trend when presented by year from 2011 to 2017. Fig. 2 shows the past month use of methamphetamine from 2011 to 2017 stratified by gender, ethnicity, urbanicity, and regionality.
As indicated in Table 1, both SKIP and RAPID samples had nearly equal proportions of males and females (47.7% vs. 54.7%, respectively), although it should be noted the RAPID sample, compared to the SKIP sample, had a lower proportion of non-whites (9.4% vs. 20.3%) and younger participants (4.4% under 25, vs. 21.1%)
Participants Interacting Directly (RAPID) Program to gather both qualitative and quantitative data. Data were analyzed for 300 RAPID participants who completed an online survey from April to May 2017 on patterns and motivations of co-occurring methamphetamine and opioid use, along with their views as experienced substance users on motivations and patterns of methamphetamine use in their localized areas. Descriptive statistics were calculated for discrete variables. Open-ended responses to two questions, “Why did you use methamphetamine AND opioids (prescription opioids OR heroin)?” and, for those who indicated they had observed increases in methamphetamine, “In your opinion, WHY has methamphetamine use increased recently among opioid users in your area?”, were entered into NVivo 10 and coded using a descriptive coding scheme. Two independent researchers participated in the coding process, which included establishing codes and meanings and cross-checking code choices. Regular discussions were held between the coders that yielded insights to refine the coding scheme and facilitate agreement on code choices. Finally, the final set of codes and their meanings were transformed into longer and more descriptive themes. The primary themes and representative quotes are included below, verbatim; the total numbers of corresponding responses are shown in parentheses. Quantitative data were analyzed using IBM SPSS Statistics v24.
4.3. Motivations for opioid + methamphetamine use Among RAPID participants, 65.0% (n = 195/300) had a lifetime history of methamphetamine use, with 76.4% of these (N = 149/195) indicating they used methamphetamine in the same time period they
Fig. 1. The percent of SKIP respondents (N = 13,521) who endorsed past month use of methamphetamine by year from 2011, quarters 2–4, to 2017, quarter 1. 16
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Fig. 2. The percent of SKIP respondents who endorsed past month use of methamphetamine by year from 2011 to 2017 by A) gender, B) race, C) urbanicity, and D) region.
energy provided by methamphetamine offset the sedation provided by opioids so that they could function and be productive, or that opioids were used to come down (e.g., sleep) from the stimulation produced by methamphetamine. It was also noted by 15.2% that if opioids were not available, then methamphetamine was used as a substitute, often as a way of managing withdrawal symptoms.
Table 1 Demographics of SKIP and RAPID samples. Group
Variable
SKIP (n = 13,521)
RAPID (n = 300)
Gender
Male Female White Nonwhite 18-24 25-34 35-44 45+
52.3% 47.7% 79.7% 20.3% 21.1% 42.7% 20.6% 15.6%
45.3% 54.7% 90.6% 9.4% 4.3% 37.5% 35.1% 23.1%
Ethnicity Age
4.4. Understanding increases in methamphetamine use We also asked RAPID participants who responded ‘Yes’ to being knowledgeable about the current drug culture/market in their area (N = 97) whether methamphetamine use had increased in recent years among opioid users in their area. Over three-fourths of the sample (76.3%, n = 74/97) indicated use had increased, and we asked them to elaborate, in their own words, the reasons behind such increases. Table 3 shows that the most common responses (N = 72; 2 provided no response) were that methamphetamine was easily accessible (38.9%) and/or cheap (30.6%), in part because it was noted to be inexpensive to make at home. Interestingly, several participants noted that it was becoming easier to find than opioids due to “restrictions” on opioids and, hence, it was used to provide some form of sought-after euphoria produced by either opioids or methamphetamine. The second most common response was that people were purposively seeking out the high of methamphetamine and opioids together because co-occurring use had become popular (37.5%) among social groups as a means of balancing the highs and lows of these two dichotomous drugs so that they could function more effectively.
were using opioids. When this latter group was asked to define their typical pattern of co-occurring methamphetamine and opioid use, the vast majority (79.9%, n = 119/149) used both substances on the same day, either ‘at the same time’ (38.9%); ‘immediately before or immediately after’ one another (9.4%); or on the ‘same day, but at different times’ (31.5%). To determine the frequency of use, RAPID participants were asked how many days in an average month they used methamphetamine while they were using opioids. The mean number of days of co-occurring use was 14.6 days per month ( ± 11.2 SD). Table 2 outlines the qualitative themes provided when participants (N = 145; 4 provided no response) were asked to describe their motivations for using both methamphetamines and opioids. While the most frequent motivator (51.0%) was the high produced by co-occurring use (i.e., a roller coaster or synergistic high), the balance these two drugs offered one another played an important role for over a third of the sample (38.6%). For example, most of these individuals noted the 17
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Table 2 Motivations for co-occuring use of methamphetamine and opioids (N = 145). Coded responses
N (%)
Representative quotes
High-seeking
74 (51.0)
Balance of effect
56 (38.6)
(1) (2) (3) (1) (2)
Availabile as Opioid Substitute
22 (15.2)
Escape from life/ Numbness
14 (9.7)
Addiction
13 (9.0)
Social Setting
9 (6.2)
(3) (4) (1) (2) (3) (1) (2) (3) (1) (2) (1) (2)
The high was like a roller coaster I enjoyed the synergetic effect I was told that it was a fabulous high, so I tried it and loved it I could function on them together I used meth to give me the rush & to have energy. I used heroin to numb myself or to get the high from the opioids. If i used too much meth id use heroin to calm down; Cause I was trying to get allot of work done energy with no pain make you be able to get stuff done Use meth sometimes to counter the drowsiness from opiods So when i couldn't use opioids because of money or availability, i used methamphetamine I would use meth when I had ran out. When I was really sick from the withdrawal and I couldn't find opioids, I would use methamphetamine Just feel numb n not worry about my problems Because I hated to be fully aware and have to percieve my surroundings, situations and life. When I was high it was like walking around in a dream state. I was numbed Escape from the reality of life Because I'm a drug addict and would do anything I could to avoid being sober. I would use any excuse I could to justify use of different drugs Because I'm a addict and it didn't matter how I got high just that I did. Initially it was just to party with socially then became addicted and had to use daily The pupil dilation and other signs that would make it obvious that I was high would be less noticable as well. Made it a lot easily to hide from people around me.
5. Discussion
elsewhere, the effects provide some relief from certain life stressors (Cicero et al., 2017; Lipari et al., 2017). Finally, more than a few participants noted that methamphetamine helped alleviate opioid withdrawal symptoms, most likely because of their dual action on dopamine reward systems in the brain (Mori et al., 2016). The precise mechanisms involved in this seemingly paradoxical effect – an excitatory drug being used to treat an opioid withdrawal syndrome which by its nature is also excitatory needs to be further examined. What is unclear from our research is why the sudden growth in the use of methamphetamine given that co-occurring use of stimulants and opioids has been noted for years (e.g., speedballs)? The most plausible explanation, as noted by many participants, is that methamphetamine is now freely available at low cost, with participants noting increases in homemade methamphetamine, contrary to media reports that this method has been replaced with Mexican methamphetamine, and accessibility to it through their opioid sources (i.e., dealers). While homemade methamphetamine was noted, some of this increase in accessibility is still likely due to the fact that Mexican drug cartels recognized a market and became a ready resource for the synthesized drug, often known as “ice” or crystal meth. Thus, inexpensive (relatively) drugs from Mexico have not only decreased the dangerous process of self-made meth but provided high-grade drugs at a very affordable rate (Loza et al., 2016; Meacham et al., 2016; U.S. Department of Justice, 2017). This sourced drug from Mexico likely explains some of the geographical specificity we observed – meth was more prevalent in the west than in the east, although there seems to be some growth in use from west to east. A second possibility to explain the increase in the
These studies indicate that there has been a marked increase in the past month use of methamphetamine in individuals with a primary indication of opioid use disorder. From 2011 to 2017, methamphetamine use nearly doubled from 18.8% in 2011 to 34.2% of all opioid users in 2017 entering a drug treatment program. Of note, among those using both methamphetamine and opioids, such use was not separated but often linked together, with the majority using both drugs within the same day, and even more concerning, doing so for nearly half the days of an average month. What makes these findings of timely importance is that they may help explain the contradiction between media reports of increases in methamphetamine use and a lack of significant change among rates reported by national surveys such as NSDUH (Center for Behavioral Health Statistics and Quality, 2015; National Institute on Drug Abuse, 2018); increases in methamphetamine use may be an issue unique to certain populations such as ours. There are two aspects of this outcome which need to be further addressed: First, what motivated couse; and second, why the steady escalation of methamphetamine uses from 2011 to 2017 and is this likely to continue to increase? With respect to co-use of opioids and methamphetamine, most users indicated that they either liked the synergistic high (i.e., the roller coaster effect) or used the drugs to balance out the effects of each other so that they could function as normally as possible. In addition to this relatively straightforward conclusion, many of our users stated that such use was a function of their addiction, noting that specific drugs were less important than use in general, or as reported here and
Table 3 Participant explanations of increases in methamphetamine use in their local areas (N = 72). Coded responses
N (%)
Representative quotes
Increased Accessibility
28 (38.9)
Increased Popularity
27 (37.5)
Low cost
22 (30.6)
Opioid restrictions
10 (13.9)
Dealer supply
8 (11.1)
(1) (2) (3) (1) (2) (3) (1) (2) (1) (2) (1) (2)
It has increased because it is so easy to make. Because it's home made, easier to get, more around. Meth has become more readily available and is cheaper in the area where I'm from. Many people can make it. Many people enjoy the effects of mixing opioids and meth. Because people are figuring out the effects of prolonging euphoric effects of meth and opiates at the same time. Meth makes it easier to be a fuctioning addict. Affordability and availability. Prices have gone from $200/gram to $80–100/g in recent years Opiods have become so expensive, whereas method can be made at home with fairly inexpensive products bought at the drug store. Opiate manufacturers making it harder to manipulate the drugs to get high, so people are looking for ways to enhance the opiates The stricter laws on opioid prescriptions (3) Due to more restrictions on pharmaceutical opioids Because most dealers sell both When the drugs people want are not readily availible they turn to drugs that are availible & drug dealers selling both kinds of drugs.
18
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Role of funding source
use of meth by those with an opioid use disorder could be related to a shortage in the supply of opioids due to supply reduction efforts, as several participants noted. Opioid users, faced with opioid withdrawal and/or their inability to get high with opioids may turn to the next best thing, so to speak. Thus, the end-point would seem to be to get high, no matter how this was achieved. It should also be noted that although one may posit that methamphetamine use is associated most strongly with heroin use, co-occurring use increased regardless of which opioid was used, a prescription opioid or illicit heroin. Our initial hypothesis which gave rise to these studies was that the supply-reduction efforts for prescription opioids (i.e., abuse-deterrent formulation, prescription monitoring programs, legislation, etc.) might lead to increased use of not only other opioids (e.g., heroin), but nonopioid euphorigenic substances. Although our results do, in fact, show a rapid escalation in methamphetamine use, attributable primarily to increases in accessibility and popularity due to the perceived high, there was some relationship to the lack of availability of opioids. These data suggest that the experience of euphoria may play a role in the selection of other opioid or non-opioid drugs if the preferred drug of choice is less accessible as it was previously. Thus, in the context of polysubstance use, it appears that the so-called “balloon theory” applies to not just to opioids but perhaps the entire use of euphorigenic drugs: decreases in use of opioids may stimulate the use of other drugs of abuse. It needs to be stressed that this remains a hypothesis and there are other possible explanations of our results. Specifically, an increase of supply of methamphetamine and “word of mouth” touting the pleasure experienced by the synergistic high produced by methamphetamines and opioids may be the simplest answer. Clearly, additional studies need to be carried out to more definitively test these competing hypotheses, but it is nevertheless clear that over a third of chronic opioid users have discovered the “benefits” of dual use of methamphetamines and opioids. Such co-occurring use of methamphetamine and opioids highlights the need for more research and understanding of polysubstance use, particularly its role in furthering prevention and treatment efforts that often are siloed into a particular drug of interest. Interventions focusing solely on opioids may not be effective for those who may engage or have already engaged in experimentation with multiple drugs of abuse. For instance, in terms of treatment, the clinical guidelines for buprenorphine indicate that such pharmacotherapy “will not necessarily have a beneficial effect on an individual’s use of other drugs” (Center for Substance Abuse Treatment, 2004). In addition, emerging substance use-related vaccines not only are substance dependent but in the case of opioids, are likely to be ineffective even against more than one class of opioid (Bremer et al., 2017; Kuppili et al., 2018; Olson and Janda, 2018). This study highlights not only the need to consider the demand side of substance use and what drives individuals to use not only one drug, but drugs in general, and how this understanding of polysubstance use, and its related outcomes, can be incorporated into prevention and treatment. There are important limitations to our studies. The SKIP and RAPID programs are retrospectives in nature which could present issues of recall. Also, since ours is a treatment-sourced sample, one could also argue that the results are not representative of those who use opioids or methamphetamine “recreationally” or those who do not seek treatment and thus, generalizability is limited. In addition, the RAPID sample included lower numbers of younger and non-white participants, populations which may demonstrate different patterns of use than what was found. These populations may require extra attention for participation in follow-up studies, which we hope to focus on as our research continues. Finally, more research is needed to validate our findings and further understand these seemingly intertwined epidemics of methamphetamines and opioids, particularly in terms of intervention and treatment delivery.
This work was supported by private funds from Washington University in St. Louis and the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System, an independent nonprofit postmarketing surveillance system that is supported by subscription fees from pharmaceutical manufacturers, who use these data for pharmacovigilance activities and to meet regulatory obligations. RADARS System is the property of Denver Health and Hospital Authority, a political subdivision of the State of Colorado. Denver Health retains exclusive ownership of all data, databases and systems. Subscribers do not participate in data collection nor do they have access to the raw data. Contributors All authors participated in analyzing and interpreting the data, and in drafting and reviewing the manuscript. All authors meet ICMJE criteria for authorship and have approved the final version of the manuscript. Conflict of interest All authors are employees of Washington University in St. Louis, which receives research funding from Denver Health and Hospital Authority. Author Cicero serves as a paid consultant on the Scientific Advisory Board of the Researched Abuse, Diversion and AddictionRelated Surveillance (RADARS®) System. None of the authors have a direct financial, commercial or other relationship with any of the subscribers of the RADARS® System. Acknowledgement None. Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.drugalcdep.2018.08. 029. References Alford, D.P., 2016. Opioid prescribing for chronic pain—achieving the right balance through education. N. Engl. J. Med. 374, 301–303. Brady, J.E., Wunsch, H., DiMaggio, C., Lang, B.H., Giglio, J., Li, G., 2014. Prescription drug monitoring and dispensing of prescription opioids. Public Health Rep. 129, 139–147. Bremer, P.T., Schlosburg, J.E., Banks, M.L., Steele, F.F., Zhou, B., Poklis, J.L., Janda, K.D., 2017. Development of a clinically viable heroin vaccine. J. Am. Chem. Soc. 139, 8601–8611. Center for Behavioral Health Statistics and Quality, 2015. Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health. HHS Publication No. SMA 15-4927, NSDUH Series H-50. Available at. http://www. samhsa.gov/data/. Center for Substance Abuse Treatment, 2004. Clinical guidelines for the use of buprenorphine in the treatment of opioid addiction. Treatment Improvement Protocol (TIP) Series 40. DHHS Publication No. (SMA) 04-3939. Rockville, MD: Substance Abuse and Mental Health Services Administration. Available at. https://www.ncbi. nlm.nih.gov/pubmed/22514846. Cicero, T.J., Ellis, M.S., 2015. Abuse-deterrent formulations and the prescription opioid abuse epidemic in the United States: lessons learned from OxyContin. JAMA Psychiatry 72, 424–430. Cicero, T.J., Dart, R.C., Indiardi, J.A., Woody, G.E., Schnoll, S., Munoz, A., 2007. The development of a comprehensive risk-management program for prescription opioid analgesics: Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®). Pain Med. 8, 157–170. Cicero, T.J., Ellis, M.S., Surratt, H.L., Kurtz, S.P., 2014. The changing face of heroin use in the United States: a retrospective analysis of the past 50 years. JAMA Psychiatry 71, 821–826. Cicero, T.J., Ellis, M.S., Kasper, Z.A., 2017. Understanding the demand side of the prescription opioid epidemic: does the initial source of opioids matter? Drug Alcohol
19
Drug and Alcohol Dependence 193 (2018) 14–20
M.S. Ellis et al.
Mexico. J. Stud. Alcohol Drugs 77, 774–781. Montemayor, S., 2018. In the Shadow of the Opioid Crisis, Meth Has Roared Back into Minnesota. Star Tribune, Minneapolis May 29. http://m.startribune.com/minnesotaopioid-deaths-rise-despite-attention-intervention/424836053/. Mori, T., Iwase, Y., Saeki, T., Iwata, N., Murata, A., Masukawa, D., Suzuki, T., 2016. Differential activation of dopaminergic systems in rat brain basal ganglia by morphine and methamphetamine. Neuroscience 322, 164–170. National Institute on Drug Abuse, 2018. National Survey of Drug Use and Health: Trends in Prevalence of Various Drugs from Ages 12 or Older, Ages 12 to 17, Ages 18 to 25, and Ages 26 or Older; 2015–2016. Available at:. https://www.drugabuse.gov/ national-survey-drug-use-health. O’Donnell, J.K., Halpin, J., Mattson, C.L., Goldberger, B.A., Gladden, R.M., 2017. Deaths involving fentanyl, fentanyl analogs, and U-47700-10 States, July–December 2016. MMWR Morb. Mortal. Wkly. Rep. 66, 1197–1202. Olson, M.E., Janda, K.D., 2018. Vaccines to combat the opioid crisis. Vaccines that prevent opioids and other substances of abuse from entering the brain could effectively treat addiction and abuse. EMBO Rep. 19, 5–9. Robles, F., 2018. Meth, the Forgotten Killer, is Back. And It’s Everywhere. Retrieved from. The New York Times. https://www.nytimes.com/2018/02/13/us/methcrystal-drug.html. Seth, P., Scholl, L., Rudd, R.A., Bacon, S., 2018. Overdose deaths involving opioids, cocaine, and psychostimulants – United States, 2015–2016. MMWR Morb. Mortal. Wkly. Rep. 67, 349–358. Soelberg, C.D., Brown Jr., R.E., Du Vivier, D., Meyer, J.E., Ramachandran, B.K., 2017. The US opioid crisis: current federal and state legal issues. Anesth. Analg. 125, 1675–1681. U.S. Customs and Border Protection, 2018. CBP Enforcement Statistics FY. Accessed at. on May 30, 2018. https://www.cbp.gov/newsroom/stats/cbp-enforcementstatistics. U.S. Department of Justice, Drug Enforcement Administration, 2017. 2017 National Drug Threat Assessment. DEA-DCT-DIR-040-17. Available at:. https://www.dea.gov/ documents/2017/10/01/2017-national-drug-threat-assessment. Wilkerson, R.G., Kim, H.K., Windsor, T.A., Mareiniss, D.P., 2016. The opioid epidemic in the United States. Emerg. Med. Clin. North Am. 34, e1–e23.
Depend. 173, S4–S10. Compton, W.M., Jones, C.M., Baldwin, G.T., 2016. Relationship between nonmedical prescription-opioid use and heroin use. N. Engl. J. Med. 374, 154–163. Dart, R.C., Surratt, H.L., Cicero, T.J., Parrino, M.W., Severtson, S.G., Bucher-Bartelson, B., Green, J.L., 2015a. Trends in opioid analgesic abuse and mortality in the United States. N. Engl. J. Med. 372, 241–248. Dart, R.C., Surratt, H.L., Cicero, T.J., Parrino, M.W., Severtson, S.G., Bucher-Bartelson, B., Green, J.L., 2015b. Supplementary Appendix: trends in opioid analgesic abuse and mortality in the United States. N. Eng. J. Med. 372, 241–248. DuPont, R.L., 2018. The opioid epidemic is an historic opportunity to improve both prevention and treatment. Brain Res. Bull. 138, 112–114. Guy Jr., G.P., Zhang, K., Bohm, M.K., Losby, J., Lewis, B., Young, R., Murphy, L.B., Dowell, D., 2017. Vital signs: changes in opioid prescribing in the United States, 2006–2015. MMWR Morb. Mortal. Wkly. Rep. 66, 697–704. International Narcotics Control Board, 2009. Report of the International Narcotics Control Board for 2008. Available at:. United Nations Publications, New York, NY. https://www.incb.org/incb/en/publications/annual-reports/annual-report-2008. html. Kuppili, P.P., Manohar, H., Menon, V., 2018. Current state of vaccines in psychiatry—a narrative review. Asian J. Psychiatry 31, 112–120. Lipari, R.N., Williams, M., Van Horn, S.L., 2017. Why Do Adults Misuse Prescription Drugs? The CBHSQ Report. Available at:. Substance Abuse and Mental Health Services Administration (US), Rockville (MD). https://www.samhsa.gov/data/sites/ default/files/report_3210/ShortReport-3210.html. Loza, O., Ramos, R., Ferreira-Pinto, J., Hernandez, M.T., Villalobos, S.A., 2016. A qualitative exploration of perceived gender differences in methamphetamine use among women who use methamphetamine on the Mexico-U.S. border. J. Ethn. Subst. Abuse 15, 405–424. Maxwell, J.C., 2011. The prescription drug epidemic in the United States: a perfect storm. Drug Alcohol Rev. 30, 264–270. McHugh, R.K., Nielsen, S., Weiss, R.D., 2015. Prescription drug abuse: from epidemiology to public policy. J. Subst. Abuse Treat. 48, 1–7. Meacham, M.C., Strathdee, S.A., Rangel, G., Armenta, R.F., Gaines, T.L., Garfein, R.S., 2016. Prevalence and correlates of heroin-methamphetamine co-injection among persons who inject drugs in San Diego, California, and Tijuana, Baja California,
20