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. Author manuscript; available in PMC: 2020 Oct 1.
Published in final edited form as: Addict Behav. 2019 May 16;97:14–19. doi: 10.1016/j.addbeh.2019.05.017

History of Regular Nonmedical Sedative and/or Alcohol Use Differentiates Substance-Use Patterns and Consequences Among Chronic Heroin Users

Tabitha EH Moses a, Mark K Greenwald a,b,*
PMCID: PMC6581601  NIHMSID: NIHMS1529812  PMID: 31112911

Abstract

Background:

Concurrent use of sedating substances (e.g. alcohol or benzodiazepines) with opioids is associated with increased negative consequences of opioid use; however, few studies have attempted to differentiate effects of using sedating substances on heroin-use outcomes. This study examines differences between heroin users who use alcohol or misuse sedatives regularly and those who do not.

Methods:

Substance-use data were collected from 367 non-treatment seeking, chronic heroin-using, 18-to-55 year-old participants. We created 4 groups based on self-reported lifetime history of regular (at least weekly) substance use: heroin only (n=95), heroin and sedatives (n=21), heroin and alcohol (n=151), and heroin, sedative, and alcohol (n=100). Chi-square analyses and ANOVAs with Bonferroni post hoc tests were used to explore differences between these groups.

Results:

Heroin users who denied lifetime alcohol or nonmedical sedative use regularly endorsed fewer consequences associated with any substance they had used. Total adverse consequences of heroin use (e.g. health problems) were significantly higher among those who misused sedatives regularly, irrespective of alcohol use history (F(3,361)=10.21; p<.001). Regular alcohol use did not independently impact heroin consequences but was associated with increased use of other substances.

Conclusions:

Although polysubstance use is normative among heroin users, the risks depend on the substances used. Regular sedative use is associated with increased heroin consequences whereas regular alcohol use is not. This study refines the investigation of polysubstance use and highlights subgroup differences depending on types of substances used regularly. This knowledge is critical for understanding substance-use motivations and creating avenues for harm reduction.

Keywords: Polysubstance use, alcohol, sedatives, heroin, opioids, consequences

1. Introduction

In 2016, almost 1 million people in the USA reported using heroin and >500,000 people had a heroin use disorder (National Institute on Drug Abuse, 2018). Opioid use disorder (OUD) is associated with numerous negative consequences including overdose, health problems, and family problems (Kronenberg et al., 2014; Madras, 2017; Moses et al., 2018b; Stone et al., 2012). Opioid overdose has become the leading cause of accidental death in the USA (Rudd et al., 2016). Risk of opioid overdose is increased by several factors, including concomitant use of sedating substances such as alcohol or benzodiazepines (BZDs) (Betts et al., 2016; Calcaterra et al., 2013; Jones et al., 2012; Park et al., 2015). Between 2014 and 2015, BZDs were associated with 27.9%, and alcohol with 13.7%, of all opioid overdose deaths (Kandel et al., 2017).

Many harms associated with heroin use are exacerbated by concomitant use of other substances (Betts et al., 2016; Coffin et al., 2003; Kreek, 1984). This is problematic because most heroin users reported using at least one other drug and nearly two thirds reported using at least three (Jones et al., 2015). Concurrent use of sedating substances with opioids is associated with increased negative consequences of opioid use (Coffin et al., 2003; Darke et al., 2009; Jann et al., 2014; Kreek, 1984; Moses et al., 2018a; Votaw et al., 2019); however, few studies have attempted to differentiate effects of alcohol and other sedative use on heroin-use outcomes. We previously found that lifetime nonmedical sedative use, but not sedative use as prescribed, was associated with greater adverse heroin-use consequences among regular heroin users (Moses et al., 2018a).

When addressing polysubstance use in OUD, there is no consensus on whether polysubstance use frequency is associated with increased risk of consequences. Data examining opioid overdose deaths focuses on substances found in the decedent’s blood (Calcaterra et al., 2013; Coffin et al., 2003; Park et al., 2015), which provides no insight into frequency of using. The mechanisms of drug interactions suggest that simultaneous use, regardless of frequency, confers the most risk (Jann et al., 2014; Kreek, 1984). Nonetheless, certain behavioral patterns associated with different frequencies of use might predict who is at risk of increased consequences. Betts et al. (2016) classified polysubstance use among people who inject drugs at least once monthly; multivariate analyses found that higher-frequency polysubstance users were at greatest risk for negative outcomes. This supports findings from Darke et al. (2009) that any past-month BZD in regular heroin users was associated with worse psychological and physical health. Votaw et al (2019) found that both past-month sedative use and past-year sedative use disorder were associated with increased psychiatric distress in participants with alcohol and/or OUD compared to those who endorsed neither. These findings suggest that presence of any polysubstance use is associated with increased risk for consequences rather than problematic use.

Heroin users report various motives for concomitant use of other substances. Studies that examine polysubstance use have identified 3 classes of motivation: 1) Enhancing psychopharmacological benefits (e.g., perceived “high”) of the primary substance by combining substances with similar mechanisms (e.g., alcohol and BZDs) or substances with different actions that may augment positive experience (e.g., opioids and BZDs); 2) Ameliorating adverse effects of drugs such as craving and withdrawal (e.g., BZDs for attenuating opioid withdrawal); 3) Self-medication for psychiatric disorders (e.g., BZDs for anxiety or alcohol for social phobia) (Connor et al., 2014; Fatséas et al.,2009; Mateu-Gelabert et al., 2017; Stein et al., 2016). Recognizing the motivations underlying polysubstance use may provide insights into optimal mechanisms for prevention and treatment in each group.

Aims and Hypothesis

This study seeks to understand how lifetime regular alcohol use and/or nonmedical sedative use impacts the severity of consequences of heroin use and whether there are clinically relevant differences between heroin users who use these additional substances. Our primary aim is to establish whether regular (at least weekly) users of alcohol or nonmedical sedatives differ in lifetime substance-use characteristics and outcomes, relative to individuals denying history of either. We hypothesize that regular use of alcohol concomitantly (not necessarily simultaneously) with heroin will have different impacts on heroin consequences than regular nonmedical sedative use, and each will have unique substance-use characteristics associated with their use. We also hypothesize that individuals reporting either regular lifetime alcohol or nonmedical sedative use (relative to those who deny ever using either regularly) will endorse a larger number of negative heroin-use outcomes. Finally, given that BZDs and alcohol each have sedating effects and can exacerbate opioid-induced respiratory depression, we hypothesize that a history of regular use of both substances will be associated with the greatest increase in health consequences of heroin use.

2. Methods

2.1. Participant selection

Non-treatment seeking, current heroin-using participants were screened for one of several behavioral pharmacology studies between 2005 and 2015 in Detroit, MI. All studies were approved by the local Institutional Review Board and conduced in accordance with the Declaration of Helsinki. Participants underwent an initial telephone screen and were invited to an in-person screening if they were 18 to 55 years of age and denied any major medical or current psychiatric disorders. Participants were included in analyses if their urine sample tested positive for opioid use (≥300 ng/ml), breath alcohol level was negative (<.02%; Alco Sensor III Breathalyzer) and they were cognitively intact, as defined by IQ score ≥ 80 on the Shipley Institute of Living Scale (Zachary, 1991).

2.2. Measures

2.2.1. Substance use patterns and progression

A standardized self-report battery (Drug History and Use Questionnaire; available on request) was used to collect information about each individual's current and previous use of alcohol, marijuana, sedatives (prescribed and nonmedical), cocaine, and heroin. For each substance, participants were asked to indicate age of initial use (defined as first time each substance was tried), age of regular use (defined as at least weekly use), frequency of current use, and route of administration.

Participants were classified as having misused sedatives if they endorsed previous nonmedical use of any BZDs, barbiturates, or clonidine; z-drugs (e.g. eszopiclone, zaleplon, and zolpidem) were not included in this assessment. For a list of the sedatives and reasoning for inclusion see (Moses et al., 2018a). We classified participants as regular nonmedical sedative users if they endorsed using any of these substances at least weekly other than exactly as prescribed by a physician. Individuals who reported they only took sedatives exactly as prescribed were excluded from this analysis.

We created 4 groups based on each heroin-using participant’s history of regular alcohol (A) or sedative (S) use: no regular alcohol or sedative use (A−/S−), only nonmedical sedative use (A−/S+), only regular alcohol use (A+/S−), and regular nonmedical sedative and alcohol use (A+/S+).

2.2.2. Heroin-use consequences and treatment seeking

Lifetime heroin-use consequences were assessed using the Heroin Use Consequences scale – a drug-specific checklist of 21 items developed in our lab (Moses et al., 2018b). Although we collected information about 21 heroin consequences, 3 were specific to school-related consequences; because the average age of heroin onset for this group was later than school age, we excluded these consequences from the detailed analysis. Drug-specific checklists were also used to assess consequences for each of the other substances. Number of negative consequences varied across substances: alcohol (20 items), marijuana (22 items), sedatives (7 items), cocaine (18 items; Lister et al., 2015). Participants were asked to indicate if they had ever experienced each consequence as a direct result of using that specific substance (e.g., accidental overdose, missed work, financial problems). We also asked participants whether they had ever sought treatment for heroin (yes [1] or no [0]) and how many times they had tried to quit using heroin.

2.3. Data analysis

To compare the 4 different groups (A−/S−, A+/S−, A−/S+, A+/S+) continuous variables were evaluated using one-way analyses of variance (ANOVAs). Bonferroni post hoc tests were used to compare groups following a significant omnibus test. Continuous variables included demographics and characteristics of substance use (e.g., age of first use). We also examined differences in rates of individual heroin consequences (e.g., overdose). To compare these 4 groups for each binary-coded (lifetime vs. never) heroin consequence, an omnibus chi-square analysis was conducted and, if significant, pairwise chi-square group comparisons followed.

All analyses were conducted with SPSS v.25. Descriptive data are presented as mean ± one standard deviation. Continuous variables with a non-normal distribution were either log10 or square root transformed prior to analysis. To improve readability, tables and figures display the non-transformed means and differences, but analyses used normally distributed variables. To control for multiple comparisons, we used the Benjamini-Hochberg procedure, which yields greater power than commonly-used approaches while controlling for false discovery (FDR) (Benjamini & Hochberg, 1995; Thissen et al., 2002). We used FDR of 5% and rejected the null hypothesis if the actual p-value was less than the adjusted p-value 0.028.

3. Results

3.1. Demographic characteristics

Data were analyzed from 367 participants. The average participant was a 42.1±9.9, African American (vs. Caucasian) (57.2%) male (71.1%), with 12.3±1.7 years of education. All participants endorsed current, regular heroin use (confirmed by UDS). Mean age of heroin initiation was 23.8±7.9, with regular use beginning about 2 years later. Average duration of heroin use was 16.0±11.2 years ranging from <1 year to 40 years, and 7.6±4.3 (out of 18) heroin-use consequences were endorsed.

Table 1 presents demographic characteristics for the 4 groups: A−/S− (n=95), A−/S+ (n=21), A+/S− (n=151), and A+/S+ (n=100). There was no significant difference in age or education but there was a significant difference in race (χ2=13.02;p=.005) and sex (χ2=19.21; p<.001). Regular nonmedical sedative users were less likely to be African American, and regular users of nonmedical sedatives or alcohol were more likely to be male.

Table 1:

Demographics of the four substance use groups. Differences in continuous (one-way ANOVA) and binary (chi-square tests) demographics are also shown.

No Regular
Alcohol or
Sedative Use		 Regular
Sedatives Only		 Regular
Alcohol
Only		 Regular
Sedative &
Alcohol Use		 F or χ2(p)
N 95 21 151 100
Age 42.0±10.9 42.2±9.3 42.3±9.6 41.7±9.5 0.096 (.962)
Race (AA) 63.2% (60)b 33.3% (7)a 63.6% (96)b 47.0% (47)a 13.02 (.005)
Sex (Male) 53.7% (51)a 76.2% (16)ab 76.2% (115)b 79.0% (79)b 19.21(<.001)
Education 12.1±2.0 12.2±1.0 12.5±1.7 12.4±1.4 1.24 (.297)
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Note: For significant overall analyses (bolded), non-shared superscripts indicate significant chi-square differences between group means (i.e., source of main effect).

3.2. Polysubstance use characteristics

Table 2 shows substance-use characteristics for the 4 groups. There were significant group differences for all substances. Individuals who had used alcohol regularly (regardless of sedative history) were more likely to have used marijuana and cocaine regularly. Polysubstance use (A+/S+ in addition to heroin) was associated with earlier age of initiating all other substances, and this group had tried to quit using cocaine more often than the A−/S− group. Across all substances there was a consistent difference between groups for total number of lifetime consequences.

Table 2:

Substance use characteristics for full sample of 367 (means ± 1 standard deviation shown unless otherwise specified)

No Regular
Alcohol or
Sedative Use		 Regular
Sedatives
Only		 Regular
Alcohol Only		 Regular
Sedative &
Alcohol Use		 F or χ2 (p)
Alcohol Regular Use % (n) 0% (0)a 0% (0)a 100% (151)b 100% (100)b N/A
Age of Regular Use N/A N/A 19.1±5.3 18.3±5.0 1.32 (.252)
Consequences 0.6±1.6a 1. l±2.0ab 3.1±4.4b 5.0±5.1c 20.55 (<.001)
Quit Attempts 0.3±2.3a 0.3±0.6ab 1.3±2.7bc 2.6±5.0c 13.57 (<.001)
Marijuana Regular Use % (n) 55.8% (53)a 66.7% (14)ab 76.2% (115)b 83.0% (83)b 20.06 (<.001)
Age of Regular Use 16.4±2.8 15.8±3.5 16.6±3.9 16.0±3.5 0.44 (.722)
Consequences 1.7±3.1a 4.2±4.5bc 2.7±4.0ac 4.2±4.2b 9.42 (<.001)
Quit Attempts 0.8±2.1 0.6±1.0 1.4±3.8 2.6±10.6 1.98 (.117)
Cocaine Regular Use % (n) 33.7% (32)a 42.9% (9)ab 53.6% (81)b 64.0% (64)b 19.12 (<.001)
Age of Regular Use 31.2±10.4b 30.0±9.4ab 27.7±8.0b 23.8±7.0a 6.54 (<.001)
Consequences 1.8±2.8a 2.7±3.1ab 3.1±3.9ab 4.3±4.3b 6.42 (<.001)
Quit Attempts 4.2±12.2a 3.4±11.3a 3.8±5.3ab 8.1±18.7b 4.12 (.007)
Non-Medical Sedatives Regular Use % (n) 0% (0)a 100% (21)b 0% (0)a 100% (100)b N/A
Age of Regular Use N/A 26.2±12.5 N/A 25.4±9.4 0.11 (.738)
Consequences 0.2±0.6a 0.6±1.0ab 0.1±0.3a 0.5±0.9b 3.81 (.011)
Quit Attempts 0.04±0.2a 2.2±6.9ab 0.03±0.2a 1.2±4.6b 3.42 (.019)
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Note: For significant overall analyses (bolded), non-shared superscripts indicate significant Bonferroni post hoc differences or chi- square differences between group means (i.e., source of main effect)

3.3. Heroin use characteristics

Table 3 presents heroin-use characteristics across the 4 groups. Participants in the A+/S− group initiated heroin use at a significantly later age than the A−/S− group and were less likely to have injected heroin. Individuals in the A+/S+ group used heroin less frequently during the month prior to screening compared to the A−/S− group. Individuals with a history of regular nonmedical sedative use (regardless of alcohol use history) endorsed more heroin consequences than those who denied regular nonmedical sedative use. Table 4 shows 18 consequences of heroin use measured and their rates of endorsement across the 4 groups. Consistent with the measure of total consequences, individuals in the A+/S− group (vs. A+/S+ group) endorsed fewer individual heroin consequences than the A−/S− group. Individuals who had regularly used sedatives nonmedically, regardless of alcohol use, endorsed 5 consequences at significantly higher rates: lost job, missed work, high at work, family problems, and driving under the influence. Heroin non-fatal overdose rates in the A−/S+ group were almost double the rates among those in either the A−/S− or the A+/S− group, and individuals in the A+/S+ group endorsed heroin non-fatal overdose at significantly higher rates than in the A+/S− group.

Table 3:

Heroin use characteristics for full sample of 367, all current regular heroin users (means ± 1 standard deviation shown unless otherwise specified)

No Regular
Alcohol or
Sedative Use		 Regular
Sedatives
Only		 Regular
Alcohol Only		 Regular
Sedative &
Alcohol Use		 F or χ2 (p)
Age of First Use 21.9±7.5a 22.1±9.0ab 25.4±7.8b 23.4±7.7ab 4.65 (.003)
Age of Regular Use 24.2±7.6a 23.8±8.4ab 27.7±8.1b 25.9±7.8ab 4.52 (.004)
Frequency of Use 142.7±129.6b 119.8±49.8ab 114.9±84.8ab 94.8±71.7a 4.03 (.008)
Total Bags/Day 4.5±2.5 6.7±3.4 5.2±4.2 4.4±2.6 2.20 (.090)
Consequences 7.4±4.8a 11.3±2.6b 7.1±4.9a 9.6±4.3b 10.21 (<.001)
Quit Attempts 9.1±16.2 12.4±21.3 7.6±14.6 14.0±23.9 2.46 (.062)
Treatment Sought? (n) 66.7% (58) 76.2% (16) 68.8% (97) 76.8% (73) 2.97 (.396)
Injection Use? (n) 73.7% (70)b 85.7% (18)b 60.9% (92)a 76.8% (76)b 11.15 (.011)
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Note: For significant overall analyses (bolded), non-shared superscripts indicate significant Bonferroni post hoc differences or chi- square differences between group means (i.e., source of main effect)

Table 4:

Heroin consequence list and participant item endorsement (N=367) by substance use group

No Regular
Alcohol or
Sedative Use		 Regular
Sedatives
Only		 Regular
Alcohol
Only		 Regular
Sedative &
Alcohol Use		 χ2(p)
Visited ER 27.2% (22) 41.2% (7) 23.6% (30) 34.9% (29) 4.58 (.206)
Overdose 29.8% (28)ab 52.4% (11)c 22.0% (33)a 40.0% (40)bc 14.08 (.003)
Health problem 22.6% (21) 33.3% (7) 16.7% (25) 28.0% (28) 6.11 (.106)
Accident/injuiy 10.8% (10) 4.8% (1) 9.3% (14) 19.0% (19) 6.78 (.079)
Arrested/legal problems 36.2% (34) 52.4% (11) 35.3% (53) 46.0% (46) 4.75 (.191)
Unexpected reaction 33.0% (31)ab 30.0% (6)ab 29.5% (44)a 46.4% (45)b 7.88 (.049)
Lost job 38.7% (36)a 66.7% (14)b 35.6% (53)a 54.0% (54)b 13.76 (.003)
Warning at work 26.6% (25)a 66.7% (14)b 28.2% (42)a 39.0% (39)a 15.71 (.001)
Missed work 46.8% (44)a 90.5% (19)b 48.3% (72)a 67.0% (67)c 21.74 (<.001)
High at work 56.4% (53)a 90.5% (19)b 52.0% (78)a 72.0% (72)b 18.67 (<.001)
Financial problems 83.0% (78)a 95.2% (20)ab 80.1% (121)a 97.0% (97)b 16.88 (.001)
Family problems 71.6% (68)a 95.2% (20)b 70.7% (106)a 92.0% (92)b 22.14 (<.001)
Drove under influe nee 66.0% (62)a 90.5% (19)b 69.5% (105)a 90.0% (90)b 21.39 (<.001)
Couldn't stop using 75.8% (72)ab 85.7%(18)ab 68.0% (102)a 83.8% (83)b 9.43 (.024)
Seizures & fits 2.2% (2) 0% (0) 5.3% (8) 6.0% (6) 3.01 (.390)
Shakes & tremors 20.4% (19) 47.6% (10) 24.3% (36) 30.3% (30) 7.69 (.053)
Memory lapse or blackouts 29.7% (27) 47.6% (10) 27.5% (41) 40.4% (40) 7.30 (.063)
Fight or quarrel 21.3% (20)a 47.6% (10)b 26.7% (40)a 42.0% (42)b 13.90 (.003)
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Note: For significant overall analyses (bolded), non-shared superscripts indicate significant chi-square differences between group means (i.e., source of main effect).

4. Discussion

This study examined whether different types of polysubstance use were associated with differing substance-use patterns and outcomes among non-treatment seeking current primary heroin users. The sample was divided into 4 groups: no history of regular alcohol or nonmedical sedative use (A−/S−), history of regular nonmedical sedative use only (A−/S+), history of regular alcohol use only (A+/S−), history of both regular nonmedical sedative and alcohol use (A+/S+).

Polysubstance use was normative among this sample of regular heroin users, consistent with the literature (Gudin et al., 2013; Hobelman & Clark, 2016; Jones et al., 2015). Although approximately one quarter of the total sample was assigned to the A−/S− group, this does not mean they did not endorse any lifetime use of these substances, and more than half of this group endorsed regular use of either marijuana or cocaine. We focused our analysis on sedatives and alcohol because those had been associated with the highest risk of adverse health outcomes when used in conjunction with opioids (or with each other) (Darke et al., 2009; Jones et al., 2012; Votaw et al., 2019). The decision to identify weekly use as the criterion for “regular use” was based on research suggesting the risks of polysubstance use may not directly relate to frequency of use (Betts et al., 2016; Darke et al., 2009; Votaw et al., 2019). Our aim was not to identify problematic use with this measure; rather, we aimed to employ weekly use as an indicator that polysubstance use likely occurred. This classification is also pragmatic because it is aligns with the measurements for polysubstance in clinics. Current policies for opioid agonist treatment (OAT) and opioid treatment for pain often include random urine testing to ensure patients are not using other substances they were not prescribed (Kampman & Jarvis, 2015; Turner et al., 2014). Many clinic policies discharge patients who test positive for unprescribed substances like BZDs, citing increased risk of overdose from concurrent use. These methods of testing do not consider whether the person has problematic or daily use – merely whether they tested positive, which could indicate as little as one past-month use. Thus, defining types of polysubstance use in people with OUD can better inform our policies and treatment of these populations.

Notably, we found at least two distinct types of polysubstance users in this population. Individuals who endorsed regular alcohol use were more likely to be regular users of other substances, whereas those who endorsed regular nonmedical sedative use endorsed a higher number of consequences associated with use of all substances. Contrary to expectations, regular alcohol use alone did not increase the number of heroin consequences compared to the reference group; regular nonmedical sedative use (alone or with regular alcohol use) was associated with significantly higher rate of endorsing 9 of the 18 consequences measured. The finding that regular nonmedical sedative use related to more heroin consequences mirrors findings of our previous study (Moses et al., 2018a). Physiologically, both sedatives and opioids decrease respiration rate, which is associated with increased rates of overdose (Dahan et al., 2010; Jolley et al., 2015; Saunders et al., 2012; Weaver, 2018; Zedler et al., 2018) and ingesting these two sedating drugs may increase levels of impairment, which may explain the higher rates of social and occupational consequences endorsed by individuals who reported having misused sedatives regularly.

The lack of independent association between regular alcohol use and heroin consequences is surprising; we also did not find an additive effect of regular nonmedical sedatives and alcohol, i.e., there was no significant difference in consequences between the regular nonmedical sedative group and the regular alcohol and nonmedical sedatives group. This suggests that regular alcohol use alone may not increase opioid-related consequences, contrary to previous results (Deering et al., 2018; Gudin et al., 2013; Hobelman & Clark, 2016; Kreek, 1984; Saunders et al., 2012). We hypothesize three potential (and not mutually exclusive) explanations for our finding. First, regular alcohol use was defined only by frequency but not quantity. Thus, individuals could have used moderate amounts of alcohol that did not produce substantial pharmacological effects or consequences in combination with heroin use. Second, the way in which polysubstance use occurs may differ depending on the type of substance used. Prior research has established that motivations for sedative use among heroin users include enhancing the “high” and self-medication for psychiatric symptoms (Connor et al., 2014; Fatséas et al., 2009; Mateu-Gelabert et al., 2017; Stein et al., 2016; Weiss et al., 1992); this type of use is more aligned with simultaneous use of the two substances. It is possible that motivations for alcohol use differ and the timeline for its use is also distinct. A third hypothesis is that, because alcohol modulates GABA receptor function through a different mechanism than BZDs or other sedatives, the interaction between it and opioids may differ.

There are subgroups of people with SUD, each with different genetic, behavioral, and physiological features (Connor et al., 2014; Jones et al., 2016; Moses et al., 2018a; Yuferov et al., 2010; Zhu et al., 2013). These differences may be associated with distinct characteristics of use, yielding information that could facilitate development of differing prevention and treatment approaches tailored to the needs of these subgroups. Understanding that each substance produces its own set of responses may help elucidate motivations underlying use of these substances. Although sedatives and alcohol are both CNS depressants subjective experiences of sedatives and alcohol differ significantly (Piasecki et al., 2011; Stein et al., 2016; Uhart et al., 2013) and motivations for their use may also diverge. Studies have shown that many people with OUD use sedatives to manage opioid withdrawal and negative affect. The present study found that individuals with a history of regular nonmedical sedative use were more likely to be injection heroin users than those who had used alcohol regularly. Individuals who use intravenously may experience increased negative consequences of heroin use and withdrawal (Bonar & Bohnert, 2016; Gossop et al., 1992; Trenz et al., 2012), so perhaps this group uses sedatives nonmedically to mitigate these symptoms. Additionally, although this group is classified as “non-medical” sedative users it is important to be aware that their use may be for self-medication of psychiatric conditions (Mateu-Gelabert et al., 2017). These psychiatric conditions and a potential lack of primary care (suggested by self-medication) may play a more direct role in the increased heroin consequences than the sedatives themselves. In contrast, those who used alcohol regularly were more likely to have used multiple other substances regularly, suggesting this type of heroin user may be motivated by general rewarding properties of the substance than its specific subjective experiences. This type of understanding could appreciably alter treatment approaches. A person who only uses heroin regularly or in combination with sedatives to mitigate withdrawal may be far more responsive to OAT alone than someone who uses heroin regularly alongside many other substances. For the latter individual, while OAT may prevent them from using heroin regularly, it may just shift their behavior toward consuming other substances. This group may benefit far more from targeted psychotherapeutic approach.

Limitations of this study should be considered. First, substance use variables were self-reported, which may introduce recall bias or a social desirability effect (i. e., report of substance use as casual rather than medical). Second, our sample does not represent the entire heroin-using population, although most heroin users nationally are not in treatment (Center for Behavioral Health Statistics, 2018). Third, only participants who denied current major physical or psychiatric problems, including severe use of other substances (e.g., sedatives, alcohol) passed the telephone screening prior to in-person assessment, resulting in selection bias. Fourth, sample size of the nonmedical sedative-only (without alcohol) group was small in absolute terms and relative to the other groups, so caution is required in drawing conclusions. Even so, these relative group sizes are consistent with US epidemiological estimates of polysubstance use (Center for Behavioral Health Statistics, 2018) and treatment admissions (TEDS) data (Arfken & Greenwald, in preparation). Fifth, data collected provide only cross-sectional lifetime use information for specific substances and their consequences. Thus, we cannot make causal inferences or determine whether certain substances were used simultaneously, or whether the regular alcohol users engaged in binge-pattern drinking. Sixth, we did not collect data on motivations for use, which could have included psychiatric complications. Although a subset of this sample had psychiatric interview data, the sample size was too small for analysis. Last, there were racial and sex differences in sedative use. Due to other racial differences in our population’s substance-use characteristics (Moses et al., under review), we cannot exclude the possibility that some differences observed were related to race instead of (or in addition to) sedative use.

In conclusion, this analysis identified significant differences in substance-use characteristics and consequences among heroin users based on their history of regular use of nonmedical sedatives or alcohol. This study further highlights the risk of nonmedical sedative use in conjunction with opioids but calls into question the reality of this concern with respect to alcohol. This study showed at least 3 distinct groups of heroin user based on their history of regular use of other substances. Awareness of these subtypes may improve understanding of the multiple motivations associated with polysubstance use and provide healthcare workers with the appropriate tools and to reduce risky behaviors in this population. Given the lack of temporal tracking in this study, it was not possible to confirm that the regular use of these substances occurred over the same time periods. Future studies should focus on the temporal relationship in polysubstance use to better understand the risks and motivations and directly address motivations behind concomitant substance use.

Highlights.

  • Polysubstance use is typical among regular heroin users

  • Heroin users who regularly misuse sedatives have increased heroin consequences

  • Regular alcohol use does not independently impact heroin consequences

  • Those who use alcohol regularly are more likely to regularly use other substances

Acknowledgements:

The authors thank Ken Bates for recruiting participants and Debra Kish, Joi Moore, Melissa Williams, Elorie Eggleston, Hayley Harrison, and Lisa Sulkowski for data collection and management.

Role of Funding Sources: NIH grants R01 DA015462 and R21 DA044946 (to MKG) from the National Institute on Drug Abuse, Helene Lycaki/Joe Young, Sr. Funds (State of Michigan), and the Detroit Wayne Mental Health Authority supported this research. Funding sources had no role in the design or conduct of this study, nor in the preparation of this manuscript.

Footnotes

Conflict of Interest: The authors declare no conflict of interest with respect to the conduct or content of this work.

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