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Selection of recent research papers on ADHD and substance use

Compiled by Al Turner, Owner of the ADDICT-L@LISTSERV.KENT.EDU


o Levin, F.R., & Kleber, H.D. (1995). Attention-deficit hyperactivity disorder and substance abuse: relationships and implications for treatment. Harvard Review of Psychiatry, 2(5), 246-258.
Attention-deficit hyperactivity disorder (ADHD) and substance-use disorders are related to each other in a variety of ways. Although within the child-psychiatry literature earlier investigations were inconsistent regarding such a link, recent prospective studies that followed hyperactive children and normal controls into adulthood have found that hyperactive adults with a history of ADHD are more likely than controls to have substance-use disorders. The substance-abuse literature is less consistent regarding the potential association between ADHD and substance abuse. However, recent studies suggest that persons with a substance-use disorder, and particularly those with a cocaine-use disorder, may be more likely than the general population to have a childhood history of ADHD. Some of the inconsistency regarding this association is due to differences in diagnostic criteria, type of assessments used, and reliability of information obtained. Each of the potential relationships that may exist between ADHD and substance abuse has treatment implications for the clinician. Pharmacological as well as nonpharmacological approaches deserve further investigation. Because pharmacotherapy is a central component in the treatment of childhood ADHD, clinicians designing a strategy to treat both a substance-use disorder and ADHD need to consider pharmacological interventions. At present, the literature on pharmacological treatment for childhood ADHD is extensive and that for adult ADHD is growing; information regarding the treatment of cocaine abuse and concomitant ADHD symptoms remains limited.
o Horner, B.R., & Scheibe, K.E. (1997). Prevalence and implications of attention-deficit hyperactivity disorder among adolescents in treatment for substance abuse. Journal of the American Academy of Child & Adolescent Psychiatry, 36(1), 30-36.
OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is overrepresented among adults and adolescents in treatment for substance abuse. This study was designed to assess the prevalence of ADHD and to elucidate differences among adolescent substance abusers relative to ADHD symptomatology.

METHOD: The Wender Utah Rating Scale and the Self-Evaluation (Teenager's) Self-Report were used to evaluate childhood history of ADHD and current symptoms, respectively, and the Child Attention Problems Scale was completed by treatment program clinicians. A quantitative substance use history and a subjective substance use interview were also administered.

RESULTS: A total of 50% of 14 females and 16 males, ranging in age from 14 to 19, met study criteria for ADHD. ADHD subjects began drug use at an earlier age, had more severe substance abuse, and had a more negative self-image prior to drug use and improved self-image with drug use. They experienced more negative affective responses related to substance use and more drug craving and attentional difficulties in treatment than control subjects.

CONCLUSIONS: The results support a substantial comorbidity of ADHD among adolescent substance abusers, with indications of drug use for self-medication. Counselling for ADHD and medication may be indicated to improve treatment outcome and future functioning.

o Carroll, K.M., Rounsaville, B.J. (1993). History and significance of childhood attention deficit disorder in treatment-seeking cocaine abusers. Comprehensive Psychiatry, 34(2), 75-82.
Thirty-five percent of 298 treatment-seeking cocaine abusers met DSM-III-R criteria for childhood attention deficit hyperactivity disorder (ADHD). Subjects with childhood ADHD were likely to be male (78%), meet Research Diagnostic Criteria (RDC) for conduct disorder (93%) and antisocial personality disorder (47%), and report a history of conduct disorder in first-degree relatives. With respect to those without the disorder and regardless of co-occurrence with sociopathy, cocaine abusers with childhood ADHD were younger at presentation for treatment and reported more severe substance use, earlier onset of cocaine abuse, more frequent and intense cocaine use, intranasal rather than freebase or intravenous use of cocaine, higher rates of alcoholism, and more previous treatment. This pattern of cocaine use is consistent with clinical descriptions of self-medication of residual symptoms of ADHD in cocaine abusers. Data from this study suggest that there may be more cocaine abusers with a history of ADHD than previously recognized in clinical samples of cocaine users, and that these individuals may differ in clinically meaningful ways from those without childhood ADHD. Moreover, the poorer outcome of subjects with ADHD in this sample underlines the importance of identifying and treating residual symptoms of ADHD in cocaine abusers.
o Cocores, J.A., Davies, R.K., Mueller, P.S., & Gold, M.S. (1987). Cocaine abuse and adult attention deficit disorder. Journal of Clinical Psychiatry, 48(9), 376-377.
Cocaine increases dopaminergic tone in the central nervous system, and hyperprolactinemia has been found in chronic cocaine abusers. Dopamine depletion is believed to result from chronic cocaine abuse. Dopamine deficiency has also been associated with attention deficit disorder (ADD) in adults, and dopamine agonists have been effective in the treatment of ADD. Four case reports of cocaine addiction and ADD are presented. ADD was assumed to play an etiologic role in cocaine abuse, and it was postulated that the patients might in part have been self-medicating a dopamine-deficient state. In addition, cocaine addicts without a premorbid history of ADD may experience a temporary cocaine-induced ADD state. In both cases, the dopamine agonist bromocriptine was highly effective for treating ADD and promoting cocaine abstinence. Restoration of the presumed dopamine deficit may permit an easier course of rehabilitation by improving the patient's ability to participate in therapeutic programs.
o Weiss, R.D., Pope, H.G. Jr, & Mirin, S.M. (1985). Treatment of chronic cocaine abuse and attention deficit disorder, residual type, with magnesium pemoline. Drug & Alcohol Dependence, 15(1-2), 69-72.
Research suggests that attention deficit disorder (ADD) may persist into adulthood, perhaps predisposing certain individuals to stimulant abuse. The authors describe two adults with chronic cocaine abuse and apparent residual ADD. After failing to respond to conventional treatment modalities, these patients were administered magnesium pemoline. Both displayed a sustained reduction in their cocaine use, without abusing pemoline. This finding suggests that the diagnostic assessment of cocaine abusers should include a search for a history of ADD. A carefully selected subgroup of this population may benefit from treatment with other stimulant medications.
o Gawin, F., Riordan, C., & Kleber. H. (1985). Methylphenidate treatment of cocaine abusers without attention deficit disorder: a negative report. American Journal of Drug & Alcohol Abuse, 11(3-4), 193-197.
Five cocaine abusers without diagnoses of Attention Deficit Disorder (ADD) were treated with methylphenidate in an open trial. In contrast to previously described patients with ADD, none of these patients showed clinical improvement or decreased cocaine use.
o Biederman, J., Wilens, T., Mick, E., Faraone, S.V., Weber, W., Curtis, S., Thornell, A., Pfister, K., Jetton, J.G., & Soriano, J. (1997). Is ADHD a risk factor for psychoactive substance use disorders? Findings from a four-year prospective follow-up study. Journal of the American Academy of Child & Adolescent Psychiatry, 36(1), 21-29.
OBJECTIVE:To evaluate whether attention-deficit hyperactivity disorder (ADHD) is a risk factor for psychoactive substance use disorders (PSUD), attending to issues of psychiatric comorbidity, family history, and adversity.

METHOD: Using assessments from multiple domains, the authors examined 140 ADHD and 120 normal control subjects at baseline and 4 years later. Drug and alcohol abuse and dependence were operationally defined.

RESULTS: No differences were detected in the rates of alcohol or drug abuse or dependence or in the rates of abuse of individual substances between the groups; both ADHD and control probands had a 15% rate of PSUD. Conduct and bipolar disorders predicted PSUD, independently of ADHD status. Family history of substance dependence and antisocial disorders was associated with PSUD in controls but less clearly so in ADHD probands. Family history of ADHD was not associated with risk for PSUD. ADHD probands had a significantly shorter time period between the onset of abuse and dependence compared with controls (1.2 years versus 3 years, p < .01).

CONCLUSIONS: Adolescents with and without ADHD had a similar risk for PSUD that was mediated by conduct and bipolar disorder. Since the risk for PSUD has been shown to be elevated in adults with ADHD when compared with controls, a sharp increase in PSUD is to be expected in grown-up ADHD children during the transition from adolescence to adulthood.
o Biederman, J., Wilens, T., Mick, E., Milberger, S., Spencer, T.J., & araone, S.V. (1995). Psychoactive substance use disorders in adults with attention deficit hyperactivity disorder (ADHD): effects of ADHD and psychiatric comorbidity. American Journal of Psychiatry, 152(11), 1652-1658.
OBJECTIVE: The authors evaluated the association between attention deficit hyperactivity disorder (ADHD) and psychoactive substance use disorders in adults with ADHD, attending to comorbidity with mood, anxiety, and antisocial disorders. It was hypothesised that psychiatric comorbidity would be a risk factor for psychoactive substance use disorders.

METHOD: Findings for 120 referred adults with a clinical diagnosis of childhood-onset ADHD were compared with those for non-ADHD adult comparison subjects (N =3D 268). All childhood and adult diagnoses were obtained by structured psychiatric interviews for DSM-III-R.

RESULTS: There was a significantly higher lifetime risk for psychoactive substance use disorders in the ADHD adults than in the comparison subjects (52% versus 27%). Although the two groups did not differ in the rate of alcohol use disorders, the ADHD adults had significantly higher rates of drug and drug plus alcohol use disorders than the comparison subjects. ADHD significantly increased the risk for substance use disorders independently of psychiatric comorbidity. Antisocial disorders significantly increased the risk for substance use disorders independently of ADHD status. Mood and anxiety disorders increased the risk for substance use disorders in both the ADHD and comparison subjects, but more demonstrably in the comparison subjects.

CONCLUSIONS: Although psychiatric comorbidity increased the risk for psychoactive substance use disorders in adults with ADHD, by itself ADHD was a significant risk factor for substance use disorders. More information is needed to further delineate risk and protective factors mediating the development of substance use disorders in persons with ADHD.

o Milberger, S., Biederman, J., Faraone, S.V., Wilens, T., & Chu, M.P. (1997) Associations between ADHD and psychoactive substance use disorders. Findings from a longitudinal study of high-risk siblings of ADHD children. American Journal of the Addictions, 6(4), 318-329.
This article investigates the relationship between attention-deficit/hyperactivity disorder (ADHD) and psychoactive substance use disorders (PSUD) in siblings of ADHD and normal-control probands and addresses issues of psychiatric comorbidity and gender. Using DSM-III-R structured diagnostic interviews and blind raters, the authors conducted a 4-year follow-up of siblings. ADHD and male gender predicted higher rates and an earlier onset of PSUD after adjusting for high-risk status, other psychiatric disorders, and age. Risk was particularly high if the siblings had ADHD plus conduct disorder. This study's findings confirms the authors' prior report high-lighting the importance of drug and alcohol prevention and cessation programs aimed at ADHD youth and their siblings, particularly those with comorbid conduct disorder.
o Wilens, T.E., Biederman, J., Mick, E., Faraone, S.V., & Spencer, T. (1997). Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. Journal of Nervous & Mental Disease, 185(8), 475-482.
We evaluated the association between attention deficit hyperactivity disorder (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD. We compared 120 referred adults having a clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All diagnoses were obtained using DSM-III-R based structured psychiatric interviews. We used group comparisons of age at onset and Cox proportional hazard models to examine the development of PSUD over time. ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar disorders conferred a significantly increased risk for early onset PSUD independently of ADHD. Psychiatric disorders commonly emerged before the onset of PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD. In addition, comorbidity with conduct and juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non-ADHD individuals. These findings confirm and extend previous findings documenting important associations between PSUD and psychiatric comorbidity including persistent ADHD.
o Coger, R.W., Moe, K.L., & Serafetinides, E.A. (1996). Attention deficit disorder in adults and nicotine dependence: psychobiological factors in resistance to recovery? Journal of Psychoactive Drugs, 28(3), 229-240.
The addictive nature of nicotine appears to depend on a number of psychobiological factors. This study explores the psychoactive effects of nicotine in relationship to the particular dysphoric aspects of Attention Deficit Disorder as a coincident factor in nicotine dependence and resistance to treatment. The psychological and behavioral effects of nicotine directly correspond to reduction in symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) and the neurochemical effects of nicotine are qualitatively similar to stimulant medications used to treat ADHD. Aspects of the treatment of nicotine or other addictions in such comorbid situations are discussed in the context of self-medication.
o Conners, C.K., Levin, E.D., Sparrow, E., Hinton, S.C., Erhardt, D., Meck, W.H., Rose, J.E., & March, J. (1996). Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD). Psychopharmacology Bulletin, 32(1), 67-73.
Nicotine, like the psychostimulants methylphenidate and dextroamphetamine, acts as an indirect dopamine agonist and improves attention and arousal. Adults and adolescents with attention deficit hyperactivity disorder (ADHD) smoke much more frequently than normal individuals or those with other psychiatric conditions, perhaps as a form of self-medication for ADHD symptoms. Nicotine might therefore have some value as a treatment for ADHD. The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n =3D 6) and nonsmokers (n =3D 11) diagno= sed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.
o Milberger, S., Biederman, J., Faraone, S.V., Chen, L., Jones, J. (1997). ADHD is associated with early initiation of cigarette smoking in children and adolescents. Journal of the American Academy of Child & Adolescent Psychiatry, 36(1), 37-44.
OBJECTIVE: The association between attention-deficit hyperactivity disorder (ADHD) and cigarette smoking in children and adolescents was evaluated.

METHOD: Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n =3D 128) and non-ADHD comparison boys (n =3D 109) followed prospectively for 4 years into mid-adolescence. Information on cigarette smoking was obtained in a standardized manner blind to the proband's clinical status. Cox proportional hazard models were used to predict cigarette smoking at follow-up using baseline characteristics as predictors.

RESULTS: ADHD was a significant predictor of cigarette smoking at follow-up into mid-adolescence. Our findings also revealed that ADHD was associated with an early initiation of cigarette smoking. This was the case even after controlling for socioeconomic status, IQ, and psychiatric comorbidity. In addition, among children with ADHD, there was a significant positive association between cigarette smoking and conduct, major depressive, and anxiety disorders.

CONCLUSIONS: ADHD, particularly the comorbid subtype, is a significant risk factor for early initiation of cigarette smoking in children and adolescents. Considering the prevalence and early childhood onset of ADHD, these findings highlight the importance of smoking prevention and cessation programs for children and adolescents with ADHD.

o Milberger, S., Biederman, J., Faraone, S.V., Chen, L., Jones, J. (1997). Further evidence of an association between attention-deficit/hyperactivity disorder and cigarette smoking. Findings from a high-risk sample of siblings. American Journal of the Addictions, 6(3), 205-217.
The authors investigated the relationship between attention-deficit/hyperactivity disorder (ADHD) and cigarette smoking in siblings of ADHD and non-ADHD probands. They conducted a 4-year follow-up of siblings from ADHD and control-group families. In the siblings of ADHD probands, ADHD was associated with higher rates and earlier onset of cigarette smoking. There was also a significant positive association between cigarette smoking and conduct disorder, major depression, and drug abuse in the siblings, even after adjusting for confounding variables. Moreover, smoking was found to be familial among ADHD families but not control-group families. Our findings indicate that ADHD is a risk factor for early initiation of cigarette smoking in the high-risk siblings of ADHD probands.
o Schubiner, H., Tzelepis, A., Isaacson, J.H., Warbasse, L.H. 3rd, Zacharek, M., & Musial, J. (1995). The dual diagnosis of attention-deficit/hyperactivity disorder and substance abuse: case reports and literature review. Clinical Psychiatry, 56(4), 146-150.
BACKGROUND: It is now recognized that attention-deficit/hyperactivity disorder (ADHD) may persist into adulthood. A number of studies have found an association between ADHD and substance abuse. This article describes three adult patients with both ADHD and substance abuse who were treated successfully with psychostimulants. A review of the relevant literature is included.


METHOD: The patients were drawn from a university-based referral center for adults with ADHD. Evaluations for ADHD and substance abuse were completed. Medical therapy and follow-up were completed by the first author.

RESULTS: All of the patients responded to psychostimulants and have remained abstinent from alcohol and other drugs for the past 2 to 3 years.

CONCLUSION: This case series and review of the literature suggest that specific treatment for ADHD with psychostimulants is feasible in patients who also have substance abuse. Future studies should evaluate the prevalence of this "dual diagnosis" and the efficacy of differing management strategies.

o Comings, D.E. (1994). Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. I. Drug abuse. Drug & Alcohol Dependence, 35(1), 1-16.
There have been relatively few studies of genetic factors in drug abuse. Childhood Attention Deficit Hyperactivity Disorder (ADHD) has been implicated as a risk factor, and pedigree studies of Tourette Syndrome (TS), a hereditary impulse disorder closely related to ADHD, show an increased prevalence of substance abuse in relatives. These observations suggest the genes for TS and ADHD may play an important role in the development of drug abuse. To examine this hypothesis 217 TS probands and 328 of their relatives, 58 ADHD probands and 35 of their relatives, and 50 controls were prospectively studied using a structured questionnaire based on the Diagnostic Interview Schedule. All subjects were Caucasians 16 to 49 years of age. The responses concerning the use of 8 different drugs and 8 different symptoms of drug abuse were compared. The results showed a highly significant increase in positive responses with increased loading for the TS and ADHD genes for 6 of the 8 drugs and all of the drug abuse symptoms. The percentage of positive responses in TS probands was markedly influenced by the presence of comorbid ADHD, as well as discipline, obsessive-compulsive, or alcohol problems. These results suggest that the genes responsible for TS and ADHD play an important role in drug abuse/dependence. The dopamine D2 receptor gene (DRD2) appears to be one of these genes since variants at this locus are significantly increased in frequency in TS, ADHD, conduct disorder and drug abuse.
o Comings, D.E. (1994). Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. II. Alcohol abuse. Drug & Alcohol Dependence, 35(1), 17-24.
Prior studies have suggested childhood attention deficit hyperactivity disorder (ADHD) as a risk factor for alcohol abuse in adults. Gilles de la Tourette Syndrome, a hereditary tic and impulse disorder, is clinically and genetically similar to ADHD. To examine the hypothesis that individuals carrying the Gts gene are at increased risk to develop alcohol use problems, the same TS (Tourette Syndrome) and ADHD probands, relatives and controls used in the prior study of drug abuse were also studied using a structured questionnaire based on the Diagnostic Interview Schedule and the MAST test. The frequency of a positive response to any of 16 different questions concerning alcohol abuse showed a highly significant increase with increased genetic loading for Gts and ADHD genes. The percentage of more than one positive response in TS probands was markedly influenced by the presence of comorbid ADHD, discipline, obsessive-compulsive or drug abuse problems. Comorbid drug abuse problems were the best predictor of alcohol abuse problems. These results suggest that the genes responsible for TS and ADHD play an important role in alcohol abuse/dependence as well as drug abuse/dependence. One of the elements common to all of these disorders may be mutant genes affecting serotonin metabolism.
o Blum, K., Sheridan, P.J., Wood, R.C., Braverman, E.R., Chen, T.J., & Comings, D.E. (1995). Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics, 5(3), 121-141.
Drug and alcohol seeking behaviour has become a great global problem affecting millions of inhabitants with a cost to society in the billions. Dopaminergic reward pathways have frequently been implicated in the etiology of addictive behaviour. While other neurotransmitters have also been implicated, to date the only molecular genetic defect which has been found to associate with alcoholism, drug dependency, obesity, smoking, pathological gambling, attention-deficit-hyperactivity disorder (ADHD), Tourette syndrome, as well as other related compulsive behaviours, are the variants of the dopamine D2 receptor gene (DRD2). In this review of the available data on the subject, we report a number of independent meta-analyses that confirm an association of DRD2 polymorphisms and impulsive-additive-compulsive behaviour (IACB), which we have termed "Reward Deficiency Syndrome". While we agree that Meta-analyses of all exant studies support an association of variants of DRD2 and IACB, correct negative findings with alcoholism may be due to differences in assessing controls and inclusion/exclusion criteria for selection of diseased probands.
o Fergusson, D.M., Lynskey, M.T., & Horwood, L.J. (1993). Conduct problems and attention deficit behaviour in middle childhood and cannabis use by age 15. Australian & New Zealand Journal of Psychiatry, 27(4), 673-682.
The relationship between conduct problems and attention deficit behaviours at ages 6, 8, 10 and 12 years and the early onset of cannabis usage by the age of 15 years was studied in a birth cohort of New Zealand children. The analysis showed that while conduct problems during middle childhood were significantly associated with later cannabis use (p < 0.05) there was no association between early attention deficit behaviours and cannabis use (p > 0.40) when the associations between conduct problems and attention deficit behaviours were taken into account. It was estimated that children who showed tendencies to conduct disorder behaviour in middle childhood were between 2.1 to 2.7 times more likely to engage in early cannabis use than children not prone to conduct problems even when a range of factors including family social background, parental separation and parental conflict were taken into account. It is concluded that early conduct disorder behaviours are a risk factor for later cannabis use when due allowance is made for social and contextual factors associated with both early conduct problems and later cannabis use.

Alexander DeLuca, M.D., FASAM.
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Revised: June 16, 2001.
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