Experimental and Clinical Psychopharmacology 2011, Vol. 19, No.

2, 134 144

2011 American Psychological Association 1064-1297/11/$12.00 DOI: 10.1037/a0022859

Adverse Consequences of Acute Inhalant Intoxication

Florida State University

Eric L. Garland

University of North Carolina at Chapel Hill

Matthew O. Howard

Inhalants are widely misused by adolescents and are among the most toxic of psychoactive substances. This investigation examined the prevalence and correlates of adverse consequences of acute inhalant intoxication. Adolescent inhalant users (n 279) in residential care completed structured interviews including assessments of the characteristics of their inhalant use. Multivariate logistic and linear regression and path analyses identied correlates of adverse inhalant intoxication-related experiences. Results of this study indicated that highrisk behaviors and adverse outcomes experienced during episodes of inhalant intoxication were common in this sample. High-frequency inhalant users were signicantly more likely than moderate- and low-frequency users to experience adverse consequences of inhalant intoxication. Certain risky behaviors and consequences, such as engaging in unprotected sex or acts of physical violence while high on inhalants, were dramatically more common among high-frequency users than low-frequency users. Prior traumatic experiences, trait impulsivity, self-medication use of inhalants, and polydrug use were signicant correlates of adverse inhalant-intoxication-related consequences. Adverse events and high-risk behaviors commonly occurred during episodes of inhalant intoxication in this sample of adolescents. High-frequency inhalant users and youth who used inhalants to medicate negative affective states were at elevated risk for such events. Keywords: inhalants, antisocial, impulsivity, substance abuse, self-medication

Inhalant use is prevalent among adolescents globally and is associated with a wide range of malignant outcomes (Howard, Balster, Cottler, Wu, & Vaughn, 2008; Garland, Howard, Vaughn, & Perron, in press). In the United States, nearly 16% of 8th graders report lifetime use of inhalants. The prevalence of inhalant use approaches 40% in samples of antisocial youth (Howard & Jenson, 1999; Howard et al., 2008). Inhalant users in community, correctional, and clinical populations evidence high levels of suicidality (Freedenthal, Vaughn, Jenson, & Howard, 2007; Howard et al., 2010); mood, anxiety, personality, and substance use disorders (Wu & Howard, 2007, 2008); and antisocial behavior including early onset and interpersonally violent offending (Howard et al., 2008; Howard, Perron, Vaughn, Bender, & Garland, 2010). However, it remains unclear to what extent, if any, that inhalant use contributes directly or indirectly to social and health problems commonly observed in inhalant users. It may be, for example, that troubled youth tend to

Eric L. Garland, Trinity Institute for the Addictions, College of Social Work, Tallahassee, FL; Matthew O. Howard, School of Social Work, University of North Carolina at Chapel Hill. This study was supported in part by Grants DA021405 (Natural History, Comorbid Mental Disorders, and Consequences of Inhalant Abuse; to M.O.H.) and DA15929 (Neuropsychiatric Impairments in Adolescent Inhalant Abusers; to M.O.H.) from the National Institute on Drug Abuse. E.L.G. was supported by Grant Number T32AT003378 from the National Center for Complementary and Alternative Medicine. Correspondence concerning this article should be addressed to Eric L. Garland, 296 Champions Way, P.O. Box 3062570, Tallahassee, FL 32306-2570. E-mail: egarland@fsu.edu 134

initiate and continue inhalant use at higher rates than their nontroubled counterparts; inhalant use increases the likelihood of experiencing various adverse outcomes; or that inhalant use and associated problems are caused by a common third factor. It is also plausible that several of these processes are involved (e.g., multiproblem youth may tend to initiate inhalant use at disproportionately high rates and then experience inhalant-related problems attributable to the pharmacological actions of inhaled substances). Despite advances in characterizing the neuropharmacology of inhalant intoxication (Balster, 1998; Lubman, Yucel, & Lawrence, 2008; Riegel, Zapata, Shippenberg, & French, 2007), little is currently known about adverse psychological, social, behavioral, and health consequences of acute inhalant intoxication under conditions approximating recreational inhalant use. For ethical reasons, few contemporary laboratory studies of humans have examined deleterious effects of acute inhalant intoxication. Even if such studies were readily available, their ndings would likely have limited generalizability, because many adverse inhalant-related experiences are observed only in the naturalistic settings where inhalant use typically occurs. Ethnographic microanalyses of inhalant use are needed to identify antecedents, concomitants, and adverse consequences of this practice across different contexts of use, populations of inhalant users, and specic inhalants of abuse. As the rst systematic effort to examine adverse consequences of acute inhalant intoxication we did the following: (a) examined the nature and prevalence of adverse outcomes and high-risk behaviors occurring during episodes of acute inhalant intoxication in adolescent inhalant users; (b) compared low-, moderate-, and high-frequency adolescent in-

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halant users in terms of their absolute and relative risks for adverse outcomes and high-risk behaviors during episodes of acute inhalant intoxication; (c) identied signicant demographic, psychiatric, and substance-related correlates of adverse inhalant-intoxication-related outcomes in controlled multivariate analyses; and (d) tested a theoretical model predicting the occurrence of adverse outcomes during episodes of inhalant intoxication. We hypothesized that adverse consequences of inhalant intoxication would be prevalent in this sample of antisocial youth, positively correlated with lifetime frequency of inhalant use, and predicted by a range of inhalantspecic and more general psychosocial factors. Method This study examined 279 adolescent inhalant users identied in a larger survey of adolescents (n 723) residing in 32 Missouri Division of Youth Services (DYS) residential care facilities (726 total beds) in 2004. In 2004, 1,277 youth, ages 13 to 17, were committed by juvenile courts to DYS for treatment of antisocial behavior: 81.2% were male, 117 (9.2%) had committed the most serious (Class A and B) felonies, 531 (41.6%) had committed less serious (Class C and D) felonies, 512 (40.1%) had committed misdemeanors, and 117 (9.2%) were committed for juvenile offenses (i.e., offenses that would not be offenses if committed by adults, such as running away from home). More than 80% of DYS residents in 2004 were committed for less serious felonies (e.g., drug crimes, theft) or misdemeanors (e.g., probation violations) (Division of Youth Services, 2004). Each of the youth in the survey sample of 723, which constituted 97.7% of DYS residents at the time interviewing was conducted, completed face-to-face structured psychiatric interviews. Thus, the present study is nearly a census of the state population of adolescent inhalant users in DYS care at the time the survey was completed and constitutes a large, representative sample of DYS annual residents who use inhalants. The study protocol was approved by the Missouri DYS and Washington University institutional review boards and certied by the Ofce of Human Research Protection. Interview All 723 survey participants completed the Volatile Solvent Screening Inventory (Howard et al., 2008), a private, one-on-one interview assessing sociodemographics, medical history, substance use, and substance-related problems, psychiatric symptoms, prior traumatic experiences, and antisocial attitudes and behaviors. The subset of respondents who reported any lifetime inhalant use (n 279) then completed the Comprehensive Solvent Assessment Interview (CSAI, Howard et al., 2008) assessing various facets of their inhalant use histories. The questions about inhalantintoxication related high-risk behaviors and adverse outcomes were included in the CSAI. For the present investigation, the following variables were examined. Lifetime frequency of inhalant use. Respondents were questioned about their use of 55 volatile substances. For each substance, youth were asked, Have you ever inhaled

or huffed [inhalant] through your nose or mouth in an effort to get high? Most youth were familiar with the term hufng, and few respondents evidenced any difculty in understanding the meaning of the inhalant use questions. Among the inhalants assessed were ve categories of paintrelated products (e.g., paint thinner), ve types of glues or cements (e.g., airplane or model glue), one shoe product (i.e., shoe shine/polish), ve gases (e.g., propane), nine types of aerosols (e.g., air freshener), six types of cleaning agents (e.g., spot remover), and 24 miscellaneous volatile substances including nail polish, nail polish remover, correction uid, gasoline, permanent markers, and carburetor cleaner. Respondents who reported any use of one or more of these 55 inhalants with the intention of getting high were considered lifetime inhalant users. Inhalation of nitrites, nitrous oxide, and nonpsychoactive gases (e.g., helium, bottled oxygen) was not, for the purposes of this investigation, considered inhalant use, consistent with current diagnostic practices (American Psychiatric Association, 2000). If youth reported lifetime use of a specic inhalant, they then were asked whether they had gotten high when they used the inhalant (yes or no) and about the number of occasions on which they had used the inhalant in their lifetime (1 5, 2 5 to 10, 3 11 to 99, 4 100). Total lifetime inhalant use frequency scores were then computed by summing individual inhalant lifetime frequency of use scores. For example, youth who had used one inhalant on ve to 10 occasions would receive a score of 2, whereas respondents who had used each of seven different inhalants on 100 occasions would receive a score of 28.
Adverse consequences and high-risk behaviors associated with acute inhalant intoxication. Youth who had used in-

halants were queried as to whether or not they had ever experienced (yes or no) each of 28 different adverse psychosocial or health-related outcomes or engaged in various high-risk behaviors during episodes of inhalant intoxication. Youth were then asked, for each adverse outcome and high-risk behavior they reported, to indicate the number of times in their life and in the year preceding their current treatment episode they had experienced that outcome or engaged in that high-risk behavior while intoxicated on inhalants. These adverse outcomes and high-risk behaviors included the following: (a) getting into a st ght; (b) committing a property crime; (c) damaging property; (d) use of other psychoactive substances (marijuana, cocaine, ecstasy/MDMA, heroin, and getting drunk on alcohol); (e) having unprotected sex, getting sick, and vomiting; (f) having a health problem related to inhalant use; (g) thinking about suicide; (h) attempting suicide; (i) driving a motor vehicle; (j) taking foolish risks; (k) getting into trouble; (l) having your personality change for the worse; (m) saying harsh or cruel things to others; (n) doing impulsive things you regretted doing later; (o) having a friendship or other close relationship damaged by your behavior; (p) being seriously hurt, injured, or burned; (q) injuring someone else; (r) having said or done embarrassing things; (s) had a serious accident; (t) having experienced sleep problems; and (u) being arrested or incarcerated for a crime committed while under the inuence of inhalants. A total

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consequences score was computed by summing the number of afrmative responses across the 28 individual items. Because this variable was right-skewed, the following cube root constant (C) transformation was used: X (X .5)1/3. A nonsignicant KolmogorovSmirnov test suggested the transformed variable was normally distributed. Use of inhalants for self-medication. Youth were queried about their motivations for inhalant use. A prior latent class analysis of reasons for inhalant use among youth (i.e., Perron, Vaughn, & Howard, 2008) identied six items assessing motivations for inhalant use that were endorsed by youth with self-medication motives: to relax, to forget your troubles, because you were sad, lonely, or depressed, because you were having family problems, because you felt angry or frustrated at someone else, and because you felt angry or frustrated at yourself. These items were summed to produce a total inhalant self-medication scale score ( .89).
Perceived problem use of inhalants and perception of risk posed by inhalant use. Inhalant users were also asked to

rate the degree to which they viewed their own use of inhalants as problematic (0 no problem, 3 a big problem) and to what extent they believed persons who used inhalants regularly were at risk of harming themselves (0 no risk, 3 great risk). Demographic and clinical covariates. Measures of psychiatric symptoms, impulsivity, and prior trauma history, as well as demographic variables including age, gender, and race, were used as covariates in multivariate logistic regression analyses. All respondents completed the Brief Symptom Inventory (BSI), consisting of 53 items assessing the extent to which youth were bothered or disturbed (0 not at all; 4 extremely) by a variety of thoughts or feelings over the last seven days including today (Derogatis, 1993). The BSI yields a Global Severity Index of overall current psychiatric distress (possible range 0 to 212, .96) and scores for nine primary symptom dimensions: Somatization, Obsessive-Compulsive, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Paranoid Ideation, and Psychoticism. To assess the extent of antisocial attitudes and traits, participants completed the Antisocial Process Screening Device (APSD, .70) (Vitacco, Rogers, & Neuman, 2003), a 20-item scale assessing narcissism, impulsivity, and callous unemotionality. Lifetime traumatic experiences were assessed with the trauma scale of the Massachusetts Youth Screening Instrument2nd Version (MAYSI-2) (Grisso & Barnum, 2000). Youth responded yes or no to questions tapping experiences of prior trauma, and responses were summed to provide total scale scores. Finally, the total number of noninhalant drug classes used and lifetime frequency of alcohol and marijuana use were used as indices of the diversity and intensity of drug use, respectively. Analytic Strategy Pearsons 2 tests and analyses of variance were used to examine bivariate associations between inhalant use frequency groups (low-, moderate-, high-frequency users and inhalant

nonusers) and variables of interest. Multivariate logistic regression analyses were used to calculate differences in odds of experiencing each of 28 consequences and high-risk behaviors while using inhalants between low-, moderate-, and highfrequency inhalant users, controlling for key sociodemographic (i.e., age, gender, urbanicity, race, and familial receipt of welfare) and psychosocial (i.e., total current psychiatric symptoms, impulsivity, prior trauma, total number of noninhalant psychoactive substance classes used, and lifetime frequency of alcohol and marijuana use) covariates. Separate 2 2 pairwise contrasts were conducted to obtain unadjusted and adjusted ORs with 95% condence intervals. A Pearson productmoment correlation matrix was generated to examine intercorrelations between inhalant-related and other variables. Simultaneous-entry multiple linear regression analysis was conducted to identify signicant demographic and psychosocial predictors of adverse consequences and high-risk behaviors associated with acute inhalant intoxication. Residuals were checked for homoscedasticity and outliers. Multicollinearity was assessed via variance ination factor statistics. A normal P-P plot was inspected to ensure normally distributed error. To explore multivariate relationships revealed by multiple linear regression, we subsequently developed a conceptual model (available from the authors on request) based on self-medication (Khantzian, 1997) and allostatic theories of substance use (Koob & Le Moal, 2001) to guide hypothetical linkages between signicant predictors of inhalantrelated adverse consequences. This hypothetical model was tested by means of path analysis within a structural equation modeling (SEM) framework using Amos 17.0, which uses full information maximum likelihood (FIML) estimation for analysis of the variance/covariance matrix (Arbuckle, 2006). Because a small percentage of cases (a maximum of 5.4% on any variable) were missing data on variables of interest, FIML was used to estimate missing data for SEM. All indicators in this model were treated as manifest variables, and individual pathway coefcients of the error variables were set at 1 to estimate the regression model. The signicance level of individual pathways was set at p .05. Because our primary dependent variable, total number of inhalant intoxication-related adverse consequences and high-risk behaviors, was positively skewed, we used the cube root constant transformation of this variable. The overall model t was assessed by examining the 2 statistic, the Nonnormed Fit Index (NNFI; Chou & Bentler, 1995) and the Comparative Fit Index (CFI; Bentler, 1990), as well as the Root Mean Squared Error of Approximation (RMSEA) Index (Hu & Bentler, 1998). The NNFI and the CFI have typical values between 0 and 1, with a value close to 1 indicating good model t. RMSEA scores closer to 0 indicate better model t. Results Sample Characteristics Inhalant users had a mean age of 15.5 (SD 1.1), and most (84.6%) were boys. With regard to race, a substantial majority were Caucasian (75.2%), but 7.5% were African American, 7.5% were Latino, 7.1% were Biracial, and 2.6%

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were of another ethnicity. The majority of inhalant users resided in small towns or rural areas (61.1%), with the remainder living in urban (26.2%) or suburban areas (12.7%). A substantial minority (41.1%) of participants were of lower socioeconomic status as evidenced by family receipt of public assistance. Compared with inhalant users, signicantly greater proportions of inhalant nonusers resided in urban areas (53.3%) and were nonwhite (56.1%). Descriptive Findings The mean number of inhalants used by the sample was 4.8 (SD 4.1; median 3.0, range 1.0 24.0). The mean score on the frequency of lifetime inhalant use measure was 8.7 (SD 9.5, range 1 to 62, median: 5.0). Because of the non-normality of the distribution, the inhalant frequency measure was recoded into an ordinal variable with three categories ranging from low- (1) to moderate- (2) to high-frequency (3) lifetime use. The new lifetime frequency measure had a mean of 1.9 (SD .8) and approximated a normal distribution (skewness: .09, SE .15; kurtosis 1.4, SE .30). The three groups differing in frequency of lifetime inhalant use were similar in size and consisted of youth who obtained a value of 13 (n 95),

4 9 (n 91), and 10 62 (n 81) on the original frequency measure. Roughly speaking, the rst group consisted of experimental or low-frequency inhalant users, the second group represented moderate-frequency users, and the third group represented high-frequency users. Table 1 reports differences in demographic, psychosocial, and inhalant-use characteristics between low-, moderate-, and high-frequency inhalant users and inhalant nonusers. Highfrequency inhalant users evidenced signicantly higher levels of psychiatric symptoms, impulsivity, prior trauma, polydrug use, self-medication tendencies, and perceived problematic inhalant use than low-frequency inhalant misusers. On the whole, inhalant nonusers reported signicantly lower levels of psychiatric symptoms, impulsivity, trauma, and polydrug use than inhalant users, as well as less frequent alcohol and marijuana use. Overall, use of marijuana, taking foolish risks, getting into trouble, getting drunk on alcohol, and driving a motor vehicle were among the most prevalent consequences and risky behaviors experienced under the inuence of inhalants, whereas being involved in a serious accident, attempting suicide, injecting intravenous drugs, using ecstasy, and using heroin were the least prevalent consequences and

Table 1 Tests of Demographic, Psychosocial, and Inhalant-Related Differences Among Low, Moderate, and High-Frequency Adolescent Inhalant Users Compared With Inhalant Nonusers
Variables Demographics Male % Non-white % Urbanicity % Receipt of welfare % Age Psychosocial variables Psychiatric symptoms (GSI) Impulsivity (APSD) Prior trauma (MAYSI) Total lifetime number of non-inhalant drug classes used Lifetime frequency of alcohol use Lifetime frequency of marijuana use Inhalant-related variables Perceived problematic use of inhalants Perceived risk of inhalants Self-medication with inhalants Lifetime frequency of inhalant use Total # of inhalant-related consequences Inhalant Low Moderate High nonusers, M frequency, M frequency, M frequency, M (SD) or n (%) (SD) or n (%) (SD) or n (%) (SD) or n (%) 403 (88.4) 256 (56.1) 243 (53.3) 179 (39.9) 15.5 (1.3) 37.4 (31.5) 6.1 (2.1) 2.8 (1.6) 2.9 (2.1) 2.0 (1.5) 2.7 (1.6) 78 (82.1) 24 (25.3) 24 (25.3) 42 (44.7) 15.6 (1.0) 39.1 (25.2) 6.5 (2.1) 2.7 (1.6) 5.0 (2.7) 2.7 (1.2) 3.3 (1.2) 0.3 (0.7) 2.6 (0.8) 5.9 (5.0) 1.8 (0.9) 3.2 (3.3) 82 (90.1) 23 (25.3) 26 (28.6) 36 (40.0) 15.4 (1.2) 52.6 (35.0) 7.5 (1.8) 3.3 (1.6) 5.9 (2.7) 3.02 (1.1) 3.52 (1.0) 0.6 (1.0) 2.5 (0.9) 8.3 (6.3) 6.1 (1.7) 6.0 (4.9) 66 (81.5) 19 (23.8) 20 (24.7) 31 (38.3) 15.6 (1.3) 75.2 (42.9) 7.8 (1.9) 3.8 (1.4) 7.0 (3.0) 3.38 (1.1) 3.53 (1.1) 1.3 (1.1) 2.6 (0.8) 12.0 (5.8) 19.7 (10.5) 9.7 (6.3) F or 2 statistic 5.74 66.79 30.02 .93 1.17 33.42a,b,c,d,e 23.73a,c,d,e 11.35a,c,d,e 100.90b,c,d,e,f 33.21c,d,e,f 14.34d,e,f .001b,c 0.68 25.07a,b,c 213.26a,b,c 36.54a,b,c p(
2

or

.10 (.13) <.001 (.30) <.001 (.20) .10 (.04) .10 (.01) <.001 (.12) <.001 (.09) <.001 (.05) <.001 (.30) <.001 (.12) <.001 (.06) <.001 (.19) .10 <.001 (.16) <.001 (.62) <.001 (.22)

Note. Dunnetts post hoc comparisons were conducted for all ANOVAs: a low- and moderate-frequency inhalant users are signicantly different; b moderate- and high-frequency inhalant users are signicantly different; c low- and high-frequency inhalant users are signicantly different; d moderate-frequency and inhalant nonusers are signicantly different; e high-frequency and inhalant nonusers are signicantly different; f low-frequency and inhalant nonusers are signicantly different. Bolded values indicate the presence of a statistically signicant omnibus F-test. Effect sizes for contrasts are indicated by partial eta squared ( 2) and phi ( ) coefcients. Urbanicity was dened as residing in an urban (as opposed to rural or small town) area. F-test results reect ANOVA for the cube-root of X C transformation of total consequences. Lifetime frequency of alcohol and marijuana use was rated on a four-point scale ( 5, 5 to 10, 11 to 99, 100 days). Lifetime total frequency of inhalant use was computed by summing the lifetime frequency of use measure ( 5, 5 to 10, 11 to 99, 100 days) across all inhalant agents ever used by each inhalant user. Bolded values indicate the presence of a statistically signicant omnibus F-test.

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risky behaviors reported (see Figure 1). A series of subgroup comparisons were conducted to analyze differences in adverse psychological, medical, social, and behavioral consequences experienced by low-, moderate-, and highfrequency inhalant users. The consequence prole of inhalant intoxication differed substantially according to lifetime frequency of use (see Figure 1).
High-frequency inhalant users experienced a comparatively increased frequency of adverse consequences and high-risk behaviors during inhalant intoxication. High-frequency in-

halant users were signicantly more likely than moderateand low-frequency users to experience a wide range of adverse biopsychosocial consequences of inhalant use (see Figure 1 and Table 2). While intoxicated on inhalants, nearly three times as many high-frequency users as lowfrequency users reported committing acts of violence (50.6% to 13.7%, respectively) and vandalism (45.0% to 15.8%, respectively), and nearly two times as many high-frequency users as low-frequency users reported committing property crimes (53.1% to 18.9%, respectively) and driving a motor vehicle under the inuence (49.4% to 23.2%, respectively). Certain risky behaviors and adverse health consequences, such as having unprotected sex or suffering serious physical injury while high on inhalants, were multiplicatively more common among high-frequency

users than low-frequency users, and intravenous drug use and suicide attempts were exponentially so. Given their inhalant intoxication-related risk behaviors including unprotected sex, taking foolish risks, IV drug use, and other high-risk behaviors for sexually acquired diseases, highfrequency inhalant users may be at substantial risk for contracting and transmitting HIV, Hepatitis B, and other blood-borne and sexually transmitted diseases. After controlling for demographic, clinical, and inhalantrelated factors, the majority of the above mentioned pairwise contrasts remained statistically signicant. Among the most notable of signicant contrasts, high-frequency users were nearly 15 times more likely than low frequency users to report suicidal thoughts, 10 times more likely to report having unsafe sex, eight times more likely to have a friendship damaged by their behavior, six times more likely to commit violent acts, and more than twice as likely to drive a motor vehicle and take foolish risks while intoxicated on inhalants. Clinical Correlates of Inhalant-Related Consequences The cube-root transformed variable representing number of inhalant-related consequences experienced was positively and signicantly correlated with an array of clinically

80 70 60 Prevalence (%) 50 40 30 20 10 0 Low Moderate High

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Figure 1. Prevalence of adverse consequences and high-risk behaviors experienced during episodes of acute inhalant intoxication by adolescent inhalant users with low, moderate, and high lifetime frequency of use. Consequences are ordered from left to right on the basis of their overall prevalence in this sample of adolescent inhalant users (n 279). Brackets denote signicant differences between inhalant use frequency groups in the unadjusted odds of reporting each consequence.

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Table 2 Prevalence and Odds of Experiencing Adverse Consequences and High-Risk Behaviors During Episodes of Acute Inhalant Intoxication Across High-, Moderate-, and Low-Frequency Groups of Adolescent Inhalant Users, in Unadjusted and Adjusted Analyses Controlling for Demographic and Clinical Covariates
Response Used marijuana Taken foolish risks Gotten into trouble Got drunk on alcohol Drove a motor vehicle Said harsh or cruel things to someone Got in a st ght Committed a property crime Done something impulsive that you regretted later Said or done embarrassing things Felt nauseated and vomited Broken things or damaged property Had unsafe sex Had a friendship/relationship damaged by your behavior Had trouble sleeping, staying asleep, or nightmares Had your personality change for the worse Been physically hurt, injured, or burned Experienced health problems Injured someone else Been arrested Thought about suicide Used cocaine Been incarcerated Had a serious accident Attempted suicide Injected drugs Used MDMA Used heroin Overall Higha Moderateb Low inhalant frequency frequency frequency users n (%) users n (%) users n (%) users n (%) 140 (50.2) 121 (43.4) 110 (39.4) 108 (38.7) 98 (35.1) 91 (32.6) 82 (29.4) 82 (29.4) 79 (28.3) 78 (28.0) 74 (26.5) 74 (26.6) 59 (21.1) 50 (17.9) 50 (18.0) 48 (17.2) 42 (15.1) 36 (12.9) 36 (12.9) 36 (12.9) 33 (11.8) 32 (11.5) 25 (9.0) 24 (8.6) 19 (6.8) 15 (5.4) 13 (4.7) 6 (2.2) 54 (66.7) 48 (59.3) 46 (56.8) 52 (64.2) 40 (49.4) 34 (42.0) 41 (50.6) 43 (53.1) 35 (43.2) 31 (38.3) 32 (39.5) 36 (45.0) 35 (43.2) 30 (37.0) 24 (30.0) 23 (28.4) 23 (28.4) 19 (23.5) 22 (25.9) 19 (23.5) 19 (23.5) 20 (24.7) 14 (7.3) 12 (14.8) 13 (16.0) 10 (12.3) 8 (9.9) 4 (4.9) 50 (54.9) 42 (46.2) 39 (42.9) 31 (34.1) 36 (39.6) 32 (35.2) 28 (30.8) 20 (22.0) 26 (28.6) 31 (34.1) 27 (29.7) 22 (24.2) 17 (18.7) 15 (16.5) 19 (20.9) 17 (18.7) 11 (12.1) 9 (9.9) 7 (7.7) 12 (13.2) 13 (14.3) 10 (11.0) 8 (8.8) 8 (8.8) 5 (5.5) 2 (2.2) 3 (3.3) 2 (2.2) 31 (32.6) 26 (27.4) 23 (24.2) 22 (23.2) 22 (23.2) 24 (25.3) 13 (13.7) 18 (18.9) 17 (17.9) 13 (13.7) 15 (15.8) 15 (15.8) 7 (7.4) 4 (4.2) 7 (7.4) 8 (8.4) 7 (7.4) 8 (8.4) 8 (8.4) 5 (5.3) 1 (1.1) 2 (2.1) 3 (3.2) 4 (4.2) 1 (1.1) 2 (2.1) 2 (2.1) 0 (0.0) UOR (95% CI) A: 4.13 (2.207.76) B: 2.52 (1.394.57) A: 3.86 (2.057.27) B: 2.28 (1.244.19) A: 4.11 (2.167.83) B: 2.35 (1.264.39) A: 5.95 (3.0811.49) B: 1.71 (0.903.27) A: 3.24 (1.706.18) B: 2.17 (1.154.10) A: 2.14 (1.134.06) B: 1.61 (0.853.02) A: 6.47 (3.1213.41) B: 2.80 (1.345.85) A: 4.84 (2.479.49) B: 1.21 (0.592.46) A: 3.49 (1.766.92) B: 1.84 (0.923.68) A: 3.91 (1.878.17) B: 3.26 (1.576.75) A: 3.48 (1.717.08) B: 2.25 (1.104.58) A: 4.36 (2.158.84) B: 1.70 (0.823.53) A: 9.57 (3.9423.21) B: 2.89 (1.147.34) A: 13.38 (4.4640.13) B: 4.49 (1.4314.10) A: 5.39 (2.1813.33) B: 3.32 (1.328.33) A: 4.31 (1.8110.30) B: 2.50 (1.026.12) A: 4.99 (2.0112.37) B: 1.73 (0.644.67) A: 3.33 (1.378.10) B: 1.19 (0.443.24) A: 3.81 (1.589.16) B: 0.91 (0.322.61) A: 5.52 (1.9615.56) B: 2.73 (0.928.10) A: 28.81 (3.76220.72) B: 15.67 (2.01122.43) A: 15.25 (3.4467.58) B: 5.74 (1.2226.97) A: 6.41 (1.7723.19) B: 2.96 (0.7611.51) A: 3.96 (1.2212.80) B: 2.19 (0.647.55) A: 17.97 (2.30140.68) B: 5.47 (0.6347.72) A: 6.55 (1.3930.84) B: 1.05 (0.147.58) A: 5.10 (1.0524.73) B: 2.03 (0.269.71) AOR (95% CI) A: 2.81 (1.345.92) B: 2.22 (1.144.32) A: 2.17 (1.044.52) B: 1.69 (0.863.30) A: 4.50 (2.149.46) B: 2.30 (1.184.50) A: 5.25 (2.2812.08) B: 1.69 (0.793.59) A: 2.23 (1.044.78) B: 1.79 (0.893.60) A: 1.44 (0.683.02) B: 1.31 (0.662.59) A: 5.99 (2.6013.82) B: 2.62 (1.205.74) A: 3.39 (1.577.32) B: 0.90 (0.411.93) A: 2.68 (1.215.97) B: 1.62 (0.763.46) A: 2.51 (1.095.78) B: 2.82 (1.296.16) A: 2.00 (0.894.49) B: 1.71 (0.803.65) A: 3.29 (1.447.50) B: 1.21 (0.542.70) A: 10.07 (3.6927.49) B: 2.49 (0.926.74) A: 8.23 (2.5226.84) B: 3.00 (0.919.89) A: 2.68 (0.967.52) B: 2.32 (0.866.26) A: 2.34 (0.876.28) B: 1.78 (0.694.61) A: 2.42 (0.837.06) B: 0.99 (0.332.96) A: 2.52 (0.897.19) B: 1.07 (0.373.08) A: 2.82 (1.007.96) B: 0.65 (0.212.02) A: 5.11 (1.5416.95) B: 1.73 (0.535.72) A: 14.98 (1.83122.98) B: 11.70 (1.4494.80) A: 12.05 (2.1567.48) B: 6.51 (1.1138.35) A: 4.69 (1.1219.69) B: 1.71 (0.397.50) A: 2.69 (0.7110.23) B: 1.43 (0.385.36) A: 10.00 (1.1388.76) B: 3.94 (0.4137.52) A: 3.64 (0.6620.25) B: 0.80 (0.106.18) A: 2.20 (0.3215.27) B: 1.42 (0.1711.88)

Note. UOR unadjusted odds ratio; AOR adjusted odds ratio, controlling for sociodemographics (age, sex, urbanicity, welfare, and race) and psychosocial variables (total psychiatric symptoms, impulsivity, prior trauma, total number of non-inhalant drug classes used, and lifetime frequency of alcohol and marijuana use). Bolded odds ratios are signicant at p .05. a Odds ratio for high-frequency users reporting the presence of the consequence, compared to low-frequency users. b Odds ratio for moderate-frequency users reporting the presence of the consequence, compared to low-frequency users. No odds ratio calculated due to cell size.

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relevant factors, including BSI global psychiatric severity (r .32, p .001), impulsivity (r .24, p .001), prior trauma (r .39, p .001), total number of noninhalant drug classes used (r .36, p .001), lifetime frequency of inhalant use (r .41, p .001), self-medication with inhalants (r .44, p .001), and level of self-identied problem use of inhalants (r .46, p .001). Predictors of Adverse Psychosocial Consequences and High-Risk Behaviors Associated With Inhalant Use The transformed total consequences score was regressed on a number of demographic and clinical covariates, including inhalant use frequency, prior traumatic experiences, impulsivity, BSI global psychiatric severity index, use of inhalants for self-medication, perceived risk of harm from inhalant use, perceived problem use of inhalants, gender, age, white/nonwhite ethnicity, urban/nonurban residence, and familial receipt of public assistance (see Table 3). This set of predictors accounted for approximately 44% of the variance in total consequence scores (R2 .44), which was signicant at the p .001 level. Self-medication with inhalants was the most inuential predictor ( .26, p .001), followed by perceived problematic use of inhalants ( .22, p .001), prior trauma ( .18, p .002), total number of noninhalant drug classes used ( .18, p .01), inhalant use frequency ( .12, p .04), and impulsivity ( .11, p .04). White youth also had signicantly fewer ( .10, p .04) inhalant-related consequences than their nonwhite counterparts. Conversely, upon controlling for the aforementioned factors, BSI global severity of psychiatric symptoms, perceived harmfulness of inhalants, gen-

der, age, and receipt of public assistance were nonsignicant predictors of consequences associated with inhalant intoxication. Path Analysis of Inhalant Consequence-Related Factors After examining multivariate regression results, we excluded nonsignicant predictors from the model and posited directional relationships between signicant predictors of inhalant-intoxication-related consequences. Our proposed path model assumed that prior traumatic experiences were associated with increased frequency of inhalant use and increased impulsivity. In turn, frequency of inhalant use and impulsivity were posited to be related to elevated levels of inhalant-intoxication-related consequences and high-risk behaviors. Further, we hypothesized that prior trauma would be linked with increased self-medication tendencies, which in turn would be associated with increased problem use of inhalants. Moreover, greater problem use of inhalants and lower perceived risk of inhalant use were assumed to be related to elevated inhalant-intoxication-related consequences. Results from the testing of the hypothetical model are shown in Figure 2. All standardized regression coefcients are included, with those signicant at p .05 indicated with solid lines. Overall, the model explained 37% of the variance in inhalant-intoxication-related consequences and high-risk behaviors. The model had excellent t: 2 1.89, 3 df, p .59; NNFI 0.99, CFI 1.0, RMSEA .00 (CI: .00, .05). Given that total number of noninhalant psychoactive substances used was a signicant predictor of inhalant-intoxi-

Table 3 Simultaneous-Entry Multiple Linear Regression Evaluating Predictors of Total Adverse Consequences and High-Risk Behaviors Experienced During Episodes of Acute Inhalant Intoxication by Adolescent Inhalant Users (n 260)
B Constant Demographics Sex Age White/non-white Urbanicity Welfare Clinical variables Psychiatric symptoms (GSI) Impulsivity (APSD) Prior trauma (MAYSI) Total number of non-inhalant drug classes used Lifetime frequency of alcohol use Lifetime frequency of marijuana use Inhalant-related variables Lifetime frequency of inhalant use Self-medication with inhalants Perceived risk of inhalant use Perceived problematic pattern of inhalant use 1.35 .04 .03 .13 .06 .07 .001 .03 .06 .03 .02 .01 .01 .02 .03 .12 SE B .40 .07 .02 .06 .06 .05 .001 .01 .02 .01 .03 .03 .00 .01 .03 .03 .03 .06 .10 .05 .06 .04 .11 .18 .18 .05 .02 .12 .26 .04 .22 p value .001 .60 .26 .04 .29 .18 .53 .04 .002 .01 .42 .69 .04 .000 .41 .000

Note. Signicant predictors of total inhalant-related consequences are indicated by a bolded p value. R2 .44; B unstandardized regression coefcient; standardized regression coefcient. The cube-root of X C transformation was used for this variable.

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paring the two nested models, 2diff 25.81, df 1, p .001. Results indicated that the implied variance of the trimmed model did not conform as well to the sample covariance matrix as that of a model that included an indirect effect of trauma through impulsivity on inhalantintoxication-related consequences. Hence, the oversimplied model was rejected and the original, more robust model retained. Discussion Frequency of lifetime inhalant intoxication was associated with a wide range of adverse consequences and highrisk behaviors in this sample of adolescents. The likelihood of experiencing deleterious effects of inhalant use increased monotonically as a function of lifetime frequency of inhalant use among study participants, even after controlling for demographic, psychosocial, and substance-related variables. Although lifetime inhalant use frequency is a robust predictor of inhalant-related consequences, the elevated risk of consequences observed among high-frequency users is likely multifactorial. To further parse this complex of risk factors, regression analyses showed that youth with higher levels of prior traumatic experiences and trait impulsivity, elevated levels of polydrug use, more frequent use of inhalants, self-medication use of inhalants, and more perceived problem inhalant use have elevated risk of acute inhalant intoxicationrelated consequences. Moreover, through path analytic techniques we obtained empirical support for a number of hypothesized pathways between the foregoing risk factors that may elucidate complex interrelationships between these variables and the adverse consequences of acute inhalant intoxication. We offer the following speculation as a means of elucidating some of these potential linkages with current ndings from developmental neuroscience. Adolescence involves a number of factors associated with high-risk behaviors, including novelty and sensation-seeking, exploration, and impulsivity, that may be subserved by the cortical remodeling of sensorimotor, limbic, and prefrontal structures that occurs during this developmental period (Giedd, 2004); these neurobehavioral tendencies predispose adolescents toward risk for addictive use of psychoactive substances (Crews & Boettiger, 2009). Further, executive functions that inhibit engagement in high-risk behaviors and regulate emotional arousal do not fully develop until late adolescence or early adulthood, when prefrontal cortical maturation has been achieved (Steinberg, 2005). Risky adolescent behavior, then, may result from unchecked pubertal increases in emotional reactivity (Spear, 2009) subserved by the exaggerated neuroendocrine, autonomic, and limbic responses to affective stimuli observed among adolescents (Hare et al., 2008; Romeo, 2010; Stroud et al., 2009). Though emotional responses intensify during pubescence, prefrontal regions devoted to self-regulation remain immature until adulthood, resulting in the inability to regulate increasingly strong emotions in the face of stressful circumstances.

Figure 2. Empirical path model: predictors of inhalant-intoxication-related consequences experienced by adolescent inhalant users (n 279). Prior trauma was assessed using the MAYSI-2 lifetime traumatic experiences index. Inhalant use frequency was computed by summing the lifetime frequency of use measure ( 5, 5 to 10, 11 to 99, 100 days) across each of 55 inhalants ever used by each adolescent inhalant user. Self-medication was assessed with a six-item scale measuring agreement with self-medication motives for inhalant use. Impulsivity was measured by the Antisocial Process Screening Device Impulsivity subscale. Perceived problem use of inhalants was measured with a four-point scale assessing the degree to which adolescent inhalant users viewed their own use of inhalants as problematic (0 no problem, 3 a big problem). Total consequences Cube-root of X C transformation of the total number of afrmative responses reecting the presence of each of 28 inhalant-intoxication-related consequences and high-risk behaviors. Additional information regarding these measures is available in the methods section of this paper and in Howard et al. (2008).

cation-related consequences in multivariate regression analyses described above, this variable was added to the model. With this variable added to the model, the only previously signicant pathway that changed in statistical signicance was the direct effect of lifetime frequency of inhalant use on inhalant-intoxication-related consequences, which decreased in magnitude to become a marginally a signicant predictor of inhalant-intoxication-related consequences, ( .10, p .06). However, upon adding total number of noninhalant substances used to the model, t decreased substantially, as determined by an elevation in the Akaike Information Criterion statistic (model without psychoactive substances, AIC 49.89, model with psychoactive substances, AIC 74.02), and poorer t indices, 2 14.02, df 5, p .02; NNFI 0.98, CFI 0.98, RMSEA .05 (CI: .02, .08). Hence, this variable was removed from the hypothetical model. To determine whether an even more parsimonious model was empirically justiable, we trimmed the effect between prior trauma and impulsivity and subsequently tested a model where the effects of these two variables on inhalantintoxication-related consequences were statistically and conceptually independent. This new model had inferior t to the original model: 2 27.7, df 4, p .001; NNFI 0.93, CFI .93, RMSEA .09 (CI: .06, .12). The 2 difference test was used as an empirical means of com-

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Compounding the emotional vulnerability inherent in adolescence, exposure to repeated stressors such as traumatic experiences of violence or abuse during the critical developmental periods predicts future susceptibility to mood disorders and substance use (Anda et al., 2006) and leads to heightened stress reactivity (Bremne & Vermetten, 2001). Recurrent stress is thought to lead to allostatic load on brain structures such as the prefrontal cortex and amygdala (McEwen, 2007), resulting in a host of deleterious effects, including executive function impairments (Liston, McEwen, & Casey, 2009) and dysphoric mood (McEwen, 2003). Stress-induced dysphoria may motivate an executively impaired adolescent to pursue intoxication via inhalant agents as a means of self-medicating negative affect (Khantzian, 1997; Perron, Vaughn, & Howard, 2008). Although selfmedication may provide temporary relief from dysphoria, allostatic load incurred from prior trauma and enhanced by the pharmacological effects of psychoactive substances promotes neuroadaptation to drug effects, modulates sensitization to rewards and punishment, and intensies negative mood states (Koob & Le Moal, 2001). This allostatic process may motivate more frequent, compulsive, and/or addictive use of inhalants in physically or socially hazardous contexts. The impact of inhalant drugs on prefrontal cortex (PFC) and striatal structures (Lubman, Yucel, & Lawrence, 2008) can lead to impaired decision making and further impulsivity, fostering the problematic patterns of inhalant use as well as the high-risk behaviors and adverse consequences reported at elevated rates by the present sample. Recent research on the phenomenology of acute inhalant intoxication indicates that high-frequency inhalant use is associated with signicant increases in dysphoric mood and disinhibited behavior above basal levels (Garland & Howard, 2010). These drug effects may contribute to the adverse psychosocial and behavioral consequences of inhalant use reported in the present investigation. A model where the effect of prior trauma on inhalantrelated consequences was partially mediated by impulsivity conformed to the data better than a model without this pathway. Traumatic brain injury sustained during childhood has been shown to be predictive of cerebral atrophy, executive function impairments, and impulsive behavior observed an average of four years after the original trauma (Slawik et al., 2009), and focal lesions in the PFC are associated with later risk taking (Floden, Alexander, Kubu, Katz, & Stuss, 2008). Such ndings suggest a potential mechanism for the association between prior trauma, impulsivity, and adverse consequences of acute inhalant intoxication. It should be noted that we originally hypothesized a relationship between psychiatric symptoms and inhalantrelated consequences, yet, controlling for a set of covariates including prior trauma, self-medication tendencies, and impulsivity, this proposed association was not supported by the data. Given the pattern of zero-order correlations between these variables, the effect of psychiatric symptoms on inhalant-related consequences appears to be fully explained by the aforementioned variables. Although psychiatric symptomatology may predict inhalant-related conse-

quences, recent evidence suggests that the intoxication experiences of high-frequency inhalant users are characterized by disinhibition and negative mood states above and beyond baseline levels (Garland & Howard, 2010). Conversely, past trauma, self-medication use of inhalants, and trait impulsivity appear to be key risk factors for inhalant-related adverse consequences whose effects cannot be fully explained by inhalant use frequency. The cross-sectional nature of the data prevents causal explanations of the relationships identied by our regression and path models. Moreover, feedback processes inherent in this network of relationships preclude a sequential explanatory framework and point toward systemic explanations for the development of adverse consequences of inhalant use among at-risk adolescents. Because the present study examines the co-occurrence of inhalant use and adverse outcomes experienced during inhalant intoxication, we cannot identify causal linkages between inhalant use and the adverse outcomes experienced. Nevertheless, it is notable that highfrequency inhalant use and self-medication with inhalants predicted such outcomes after statistically controlling for other psychosocial variables, suggesting that there may be direct effects of inhalant use on the likelihood of experiencing adverse consequences. Yet, it is possible that the inhalant-using youth in the present sample are atypically antisocial and the adverse consequences and high-risk behaviors we observed may result from their general antisocial tendencies rather than their inhalant use per se. However, inhalant users identied in the general population also are found to be notably antisocial (Howard et al., 2010), and clinical and experimental studies of inhalant misuse need to be directed to service populations enriched for the presence of antisocial inhalant users such as the one we studied. Caution is warranted in any attempt to generalize these ndings to populations of antisocial youth other than those in residential treatment for antisocial behavior. Another potential limitation of the present study relates to the lifetime frequency of inhalant use measure used, which was a composite score constructed from individual ordinal assessments of the frequency of use of specic inhalants that may be less precise than an interval or ratio-level assessment of inhalant-use frequency. Yet, the low-, moderate-, and high-frequency inhalant use groups differed signicantly in the average number of inhalants used, perceived severity of problems with inhalants, self-medication use of inhalants, and in other important respects that were in the predicted directions. Furthermore, these groups were reliably distinguished in terms of the number of inhalantrelated consequences they experienced. The present investigation is also limited by the use of retrospective, selfreport measures, which are subject to social desirability bias and forgetting, factors that may lead to the underreporting of inhalant-related consequences. Similarly, given the substantial levels of inhalant use identied in this sample, self-reports may be inaccurate because of inhalant-related cognitive impairments. Despite these limitations, this rst systematic effort to examine adverse conse-

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quences of acute inhalant intoxication has the potential to inform clinical intervention with adolescent volatile substance misusers. Clearly, many moderate- to high-frequency antisocial adolescent inhalant users engage in dangerous activities with the potential to inict serious harm upon themselves or others. Of signicant concern are the intoxication-related risk behaviors that place users at apparently high risk for contracting and transmitting HIV and other blood-borne and sexually transmitted diseases. Elevated rates of unprotected sex, foolish risk-taking, and IV drug-use suggest that HIV and STD prevention interventions should be directed to this adolescent group. It remains an empirical question how treatments can best be designed to effectively prevent inhalant use and its adverse consequences, and presently there is a great need for randomized controlled trials of inhalant prevention and treatment interventions. Fortunately, a new generation of interventions is emerging that holds promise as a means of targeting the neurocognitive decits implicated in addictive disorders (e.g., Garland, Gaylord, Boettiger, & Howard, 2010; Rubio, Martinez-Gras, & Manzanares, 2009; Schoenmakers et al., 2010); such interventions may prove to be benecial means of treating inhalant use disorders and preventing inhalant-related consequences, as well. In addition to such targeted individuallevel treatments, systemic interventions (e.g., Szapocznik & Williams, 2000) are needed to address the constellation of contextual factors contributing to the initiation and maintenance of inhalant misuse. Policymakers and clinicians alike should prioritize at-risk youth, such as those examined in this study, for future inhalant prevention and treatment efforts. Prevention efforts should commence in elementary school, as inhalants are typically among the rst drugs of abuse used by youth and often are of particularly early onset in antisocial youth. Juvenile detention centers, adolescent correctional and psychiatric institutions, and adolescent drug treatment units should have a high index of suspicion for inhalant use. These are highly enriched settings for inhalant users, and interventions in these locations could have noteworthy effects at relatively low cost. Service providers in rural settings and clinicians working with psychiatrically disordered youth should also be aware of and able to intervene with inhalant-using youth at high risk for adverse inhalant-related consequences. References
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Received August 14, 2010 Revision received January 12, 2011 Accepted January 15, 2011