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1.
J Psychoactive Drugs ; 51(1): 85-92, 2019.
Article in English | MEDLINE | ID: mdl-30653394

ABSTRACT

This article outlines a liberation-focused model of addiction treatment. Drawing on the Latin root word "addictus", addiction is seen as slavery and freedom, rather than the cessation of drug and alcohol use, is proposed as a viable, alternative treatment goal. Freedom is defined as: (1) the capacity to create a life of social and internal complexity and multiplicity; (2) the ability to make choices from an array of options; and (3) the possibility of engaging in long-term, goal-directed behavior. This vision of personal liberation is then embedded within a biopsychosocial model of care and treatment. Examples of how biomedical, psychological, and social interventions can each serve to promote the goal and experience of freedom and liberation are provided. Engaging in identity projects and using harm reduction interventions and philosophies are also seen as key to this transformative journey.


Subject(s)
Behavior, Addictive/therapy , Substance-Related Disorders/therapy , Freedom , Harm Reduction/drug effects , Humans , Motivation/drug effects
2.
Alcohol Treat Q ; 30(1): 109-128, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22754086

ABSTRACT

This article is focused on improving the quality of addiction treatment. Based on observations that patients are leaving treatment too early and/or are continuing to use substances during their care, the authors propose six actions that could help reorient and revitalize this kind of clinical work: (1) conceptualize and treat addictive disorders within a psychiatric/mental health framework; (2) make the creation of a strong therapeutic alliance a core part of the healing process; (3) understand patients' addictions and other problems using models based on multiple internal parts, voices, or modes; (4) make contingency management and the use of positive reinforcement systems a standard and central practice in all treatment settings; (5) envision long-term change and healing through the lens of identity theory; and (6) integrate the growing developments in recovery culture with formal treatment.

3.
Drug Alcohol Depend ; 124(1-2): 113-20, 2012 Jul 01.
Article in English | MEDLINE | ID: mdl-22265192

ABSTRACT

BACKGROUND: Personality traits such as impulsivity and sensation seeking may contribute to the initiation and maintenance of illicit drug use. Since studies have reported higher impulsivity and sensation seeking traits in cocaine dependent subjects, we were interested in determining whether former heroin addicts in methadone pharmacotherapy with comorbid cocaine addiction have greater impulsivity than those without. METHODS: Instruments to assess impulsivity (Barratt Impulsiveness Scale version 11) and sensation seeking (Sensation Seeking Scale version V) were administered to former severe heroin addicts meeting Federal criteria for methadone maintenance pharmacotherapy with (n = 71) or without cocaine dependence (n = 31) and to 145 normal healthy (non-methadone-maintained) volunteers. RESULTS: The methadone-maintained without cocaine dependence and the methadone-maintained with cocaine dependence groups, both scored higher than did the normal volunteer group on the Barratt Impulsiveness Scale total score (p<0.001). On the Barratt Impulsiveness Scale Attentional, Nonplanning, and Motor subscales, the methadone-maintained and methadone-maintained with cocaine dependence groups scored higher than did normal volunteers with no history of drug abuse or dependence (p<0.001). There was no difference among groups on total score or any subscale of the Sensation Seeking Scale. However, males in all groups overall scored higher than did females on Disinhibition and Thrill and Adventure seeking subscales of the Sensation Seeking Scale version V (p<0.001). CONCLUSIONS: This study demonstrates higher impulsivity in former severe heroin addicts meeting criteria for or currently in stable methadone maintenance pharmacotherapy, irrespective of a positive or negative history of cocaine dependence.


Subject(s)
Cocaine-Related Disorders/psychology , Heroin Dependence/psychology , Impulsive Behavior/psychology , Adult , Cocaine-Related Disorders/complications , Cocaine-Related Disorders/rehabilitation , Female , Heroin Dependence/complications , Heroin Dependence/rehabilitation , Humans , Impulsive Behavior/complications , Male , Methadone/therapeutic use , Middle Aged , Psychiatric Status Rating Scales
4.
J Clin Psychol ; 66(2): 123-35, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20088005

ABSTRACT

Harm reduction is a new paradigm that seeks to reduce the harmful consequences of substance use and other risky behaviors without requiring abstinence. This article discusses integrative harm reduction psychotherapy, one application of harm reduction principles to psychotherapy. Seven therapeutic tasks are described with attention to clinical process, skills, and strategies. A case is presented that illustrates the application of this approach with life-threatening substance use that was related to multiple trauma and suicidal depression.


Subject(s)
Harm Reduction , Multiple Trauma/psychology , Psychotherapy , Substance-Related Disorders/psychology , Suicide/psychology , Adult , Anecdotes as Topic , Comorbidity , Female , Humans , Self Efficacy , Substance-Related Disorders/therapy
5.
Behav Genet ; 38(2): 133-50, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18181017

ABSTRACT

The tryptophan hydroxylase 2 gene (TPH2) was resequenced at the 5' upstream, coding, and 3' downstream regions, including all 11 exons in 185 subjects. Twenty-three novel and 14 known variants were identified. In a cohort of 583 consecutively ascertained subjects, including normal volunteers and those with specific addictive diseases, six common TPH2 and one TPH1 variant were genotyped. Allele frequencies of three TPH2 variants and the TPH1 variant varied significantly among the four ethnic groups within the control subjects. Of these subjects, 385 who met heroin addiction or control criteria and were of Caucasian, African-American, or Hispanic ethnicity were examined for potential association with vulnerability to develop heroin addiction. At the two locus genotype level in Hispanics, the TPH1 rs1799913 variant was found to significantly interact with the TPH2 rs7963720 variant and heroin addiction (P=0.022), and with the TPH2 rs4290270 variant and heroin addiction (P=0.011). In the African-American group, a significant association of a specific TPH2 haplotype with heroin addiction also was found (SNPHAP, P=0.004; PHASE P=0.036).


Subject(s)
Genetic Markers , Genetic Variation , Heroin Dependence/genetics , Tryptophan Hydroxylase/genetics , Black People/genetics , Cohort Studies , Exons , Female , Gene Amplification , Heroin Dependence/enzymology , Hispanic or Latino/genetics , Humans , Male , Reference Values , Severity of Illness Index , White People/genetics
6.
Addict Biol ; 12(3-4): 496-502, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17559549

ABSTRACT

There is strong evidence for a genetic contribution to individual differences in vulnerability to drug addictions. Studies have shown that the 68-base pair repeat polymorphism in the promoter region of the human prodynorphin gene contains a putative AP-1 binding site, and that three or four repeat copies result in greater transcriptional activation. Here, we report on a separate cohort of 302 subjects ascertained and characterized extensively by Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition and Addiction Severity Index criteria as: (1) a control group of 127 subjects with no history of alcohol or drug abuse or dependence; (3) a case group of 82 with cocaine dependence only; and (3) a case group of 93 with cocaine and alcohol codependence. The promoter region of the prodynorphin gene containing the repeat was amplified from genomic DNA by polymerase chain reaction and analyzed via gel electrophoresis. Statistical tests were performed with data stratified by the three major ethnic groups studied: African American, Caucasian and Hispanic. For analyses, genotypes were grouped into short (1,1; 1,2; 2,2), short/long (1,3; 2,3; 1,4; 2,4) and long (3,3; 3,4; 4,4) repeats. Deviation from Hardy-Weinberg Equilibrium in the African American control group necessitated testing for association using grouped genotypes rather than grouped alleles. In controls, a significant difference was found in grouped genotype distribution among ethnicities. We found a point-wise, but not experiment-wise across-ethnicities, significant difference in grouped genotype frequency between the cocaine/alcohol-codependent group and the controls in African Americans, with genotypes containing longer alleles found at higher frequency in the codependent group.


Subject(s)
Alcoholism/genetics , Base Pairing/genetics , Black People/genetics , Cocaine-Related Disorders/genetics , DNA/genetics , Enkephalins/genetics , Hispanic or Latino/genetics , Promoter Regions, Genetic/genetics , Protein Precursors/genetics , Tandem Repeat Sequences/genetics , White People/genetics , Alleles , Comorbidity , Female , Gene Frequency , Genotype , Humans , Male , Polymerase Chain Reaction
7.
Am J Psychiatry ; 163(11): 1993-9, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17074952

ABSTRACT

OBJECTIVE: Theory and some preliminary evidence suggest that contingency management may be an effective treatment strategy or adjunct to psychosocial treatment for methamphetamine use disorders. An experimentally rigorous investigation on the topic was provided by a large multisite trial conducted under the auspices of the Clinical Trials Network of the National Institute on Drug Abuse. METHOD: The authors report data on 113 participants who were diagnosed with methamphetamine abuse or dependence. They were randomly assigned to receive 12 weeks of either treatment as usual or treatment as usual plus contingency management. Urine samples were tested for illicit drugs, and breath samples were tested for alcohol. The reinforcers for drug-negative samples were plastic chips, some of which could be exchanged for prizes. The number of plastic chips drawn increased with each week of negative samples but was reset to one after a missed or positive sample. RESULTS: The participants in both groups remained in treatment for equivalent times, but those receiving contingency management in addition to usual treatment submitted significantly more negative samples, and they were abstinent for a longer period of time (5 versus 3 weeks). CONCLUSIONS: These results suggest that contingency management has promise as a component in treatment strategies for methamphetamine use disorder.


Subject(s)
Amphetamine-Related Disorders/therapy , Behavior Therapy/methods , Token Economy , Adult , Amphetamine-Related Disorders/psychology , Amphetamine-Related Disorders/urine , Behavior, Addictive/psychology , Behavior, Addictive/therapy , Behavior, Addictive/urine , Female , Humans , Male , Reinforcement Schedule , Substance Abuse Detection , Substance Abuse Treatment Centers , Treatment Outcome
8.
Subst Abus ; 27(1-2): 9-24, 2006 Jun.
Article in English | MEDLINE | ID: mdl-17062541

ABSTRACT

There has been a growing interest in the substance abuse treatment field in bringing together the treatment and research communities. While dialogues about logistical and philosophical issues are important, the development of shared core concepts could potentially be quite helpful in facilitating communication and creating common treatment and research goals. It is the contention of this paper that all psychosocial and, potentially, pharmacological treatments ideally address, in part or in full, three aspects of the self--the capacity to regulate emotional and behavioral expression, the ability to engage in future-oriented, goal-directed behavior, and the development of nonaddict and/or recovery-oriented identities. Examples from the research and treatment literature are provided.


Subject(s)
Alcoholism/rehabilitation , Biomedical Research , Cooperative Behavior , Patient Care Team , Substance-Related Disorders/rehabilitation , Alcoholism/psychology , Buprenorphine/therapeutic use , Goals , Humans , Internal-External Control , Narcotics/therapeutic use , Psychotherapy , Self Care/psychology , Self Psychology , Self-Help Groups , Substance-Related Disorders/psychology
9.
J Addict Dis ; 25(3): 15-25, 2006.
Article in English | MEDLINE | ID: mdl-16956865

ABSTRACT

This study examined the impact of methadone maintenance treatment on an inclusive group of adolescent and young adult opiate-dependent patients, ages 15-23, admitted over a 6-year period, during their first year in the program. Retention in treatment was the primary outcome variable, and at 12 months, 48% were still in treatment. The findings were: (a) a stepwise discriminant function analysis revealed that patients who consistently used heroin were at a greater risk of leaving treatment within the first 12 months; (b) the use of cocaine was an indicator of higher levels of heroin use in those who reached the one-year mark; (c) among patients who stayed in treatment for one year, there was a significant reduction in heroin use, a trend toward a reduction in cocaine use, and no significant impact on benzodiazepine use; and (d) the group that stayed in treatment was slightly younger than the group that left before the first year ended. There were no gender or ethnic differences between the two groups. Suggestions for interventions that might improve treatment outcome are presented.


Subject(s)
Heroin Dependence/epidemiology , Heroin Dependence/rehabilitation , Methadone/therapeutic use , Narcotics/therapeutic use , Patient Compliance/statistics & numerical data , Adolescent , Adult , Cocaine-Related Disorders/epidemiology , Demography , Drug Interactions , Female , Heroin Dependence/urine , Humans , Male , Methadone/administration & dosage , Narcotics/administration & dosage , Patient Admission/statistics & numerical data , Prevalence , Retention, Psychology , Toxicology/methods , Treatment Outcome
10.
J Addict Dis ; 25(2): 47-52, 2006.
Article in English | MEDLINE | ID: mdl-16785219

ABSTRACT

This observational study examined the antidepressant treatment patterns of a novel New York City methadone maintenance treatment program (MMTP), founded for the treatment of adolescents and now targeting young adults and older patients with special problems. The goal of the study was to investigate demographic or clinical characteristics that were associated with prescribing patterns, as well as whether antidepressant use was associated with sobriety. The method of data collection was a thorough chart review. Antidepressant treatment was significantly associated with gender, education, marital status, and relapse. However, after controlling for demographic and clinical characteristics, antidepressant treatment was not significantly associated with a reduction in relapse risk. Further research is needed to explore these relationships, as well as their generalizability to adult methadone clinics, and to examine the underlying factors that lead to similarities and distinctions in antidepressant prescribing practices between various types of clinics (i.e., general outpatient vs. methadone maintenance).


Subject(s)
Antidepressive Agents/administration & dosage , Heroin Dependence/rehabilitation , Methadone/administration & dosage , Narcotics/administration & dosage , Urban Population , Adolescent , Adult , Age Factors , Aged , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , New York City , Recurrence , Retrospective Studies , Sex Factors , Statistics as Topic , Substance Abuse Detection/statistics & numerical data , Substance Abuse Treatment Centers , Treatment Outcome
11.
J Addict Dis ; 25(1): 43-50, 2006.
Article in English | MEDLINE | ID: mdl-16597572

ABSTRACT

AIM: To evaluate whether effective methadone treatment affects cocaine use. METHODS: 421 consecutive patients admitted to a methadone maintenance clinic in Israel (1993-2002) were prospectively studied. Patients' urine samples were analyzed for cocaine during months 1 and 13. RESULTS: On admission 55(13.1%) of 421 patients had urine positive for cocaine and 366 had negative. Of the 55 cocaine-positive patients, 45(81.8%) stayed in treatment at least one year, as did 267(73%) of cocaine-negative. After one year (n=312) 31 of 45 cocaine users stopped and 25 of 267 started. Methadone dose was highest in 31 patients who stopped cocaine (176.1+/-42.1 mg/ day), followed by 14 who did not stop (161.4+/-37.5 mg/day), and 25 who started during treatment (122.9+/-48.7 mg/day), or 242 who never used cocaine (119.5+/-48.4 mg/day) (ANOVA, F=15.6, p<0.0005). CONCLUSIONS: High methadone dose may reduce cocaine use in patients addicted to both heroin and cocaine.


Subject(s)
Analgesics, Opioid/therapeutic use , Cocaine-Related Disorders/therapy , Methadone/therapeutic use , Substance Abuse Treatment Centers , Adolescent , Adult , Cocaine/urine , Cocaine-Related Disorders/urine , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged
12.
Biomed Instrum Technol ; 40(1): 72-7, 2006.
Article in English | MEDLINE | ID: mdl-16544793

ABSTRACT

Ultrasonic skin permeation using the SonoPrep (Sontra Medical Corporation, Franklin, MA) device was evaluated as a methodto reduce skin impedance for electrophystology measurements. SonoPrep treatment was compared to QuikPrep (Quinton , Inc, Bothell, WA) and mechanical abrasion with the Kendall Excel electrode release liner (Tyco Healthcare, Mansfield, MA). Five skin sites for each prepping method were treated on the backs of 10 volunteer subjects. Skin impedance was measured across the sites over 24 hours at times equal to 0 to 7 hours, 23 hours, and 24 hours. Average skin impedance for all sites and times following treatment with SonoPrep war 1.9 kiloohms (komega), with QuikPrep was 18. 7komega, and with Excel abrasion was 97.2 komega. Skin impedance was stable for 24 hours following SonoPrep treatment and declined initially following QuikPrep. Skin impedance decilned continually following Excel abrasive preparation. SonoPrep ultrasonic skin permeation reduces skin impedance to significantly decreased levels in a reproducibly consistent manner.


Subject(s)
Electrophysiology/instrumentation , Electrophysiology/methods , Skin Physiological Phenomena/radiation effects , Sonication , Electric Impedance , Equipment Design , Equipment Failure Analysis , Humans , Permeability/radiation effects , Pilot Projects , Technology Assessment, Biomedical
13.
J Clin Psychol ; 62(4): 445-58, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16470629

ABSTRACT

This article presents the Schema Therapy (Young, Klosko, & Weishaar, 2003) approach to the treatment of borderline personality disorder. Schema therapy draws on the cognitive-behavioral, attachment, psychodynamic, and emotion-focused traditions and conceptualizes patients who have borderline personality disorder as being under the sway of five modes or aspects of the self. The goal of the therapy is to reorganize this inner structure. To this end, there are four core mechanisms of change that are used in this therapy: (1) limited reparenting, (2) experiential imagery and dialogue work, (3) cognitive restructuring and education, and (4) behavioral pattern breaking. These interventions are used during the three phases of treatment: (1) bonding and emotional regulation, (2) schema mode change, and (3) development of autonomy.


Subject(s)
Borderline Personality Disorder/psychology , Borderline Personality Disorder/therapy , Psychological Theory , Psychotherapy/methods , Affect , Cognition , Humans , Impulsive Behavior/psychology , Parent-Child Relations , Psychology, Child , Punishment
14.
Arch Gen Psychiatry ; 63(2): 201-8, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16461864

ABSTRACT

BACKGROUND: Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence have improved treatment outcomes of substance abusers, but have not been widely implemented in community drug abuse treatment settings. OBJECTIVE: To compare outcomes achieved when a lower-cost prize-based contingency management treatment is added to usual care in community methadone hydrochloride maintenance treatment settings. DESIGN: Random assignment to usual care with (n = 198) or without (n = 190) abstinence incentives during a 12-week trial. SETTING: Six community-based methadone maintenance drug abuse treatment clinics in locations across the United States. PARTICIPANTS: Three hundred eighty-eight stimulant-abusing patients enrolled in methadone maintenance programs for at least 1 month and no more than 3 years. INTERVENTION: Participants submitting stimulant- and alcohol-negative samples earned draws for a chance to win prizes; the number of draws earned increased with continuous abstinence time. MAIN OUTCOME MEASURES: Total number of stimulant- and alcohol-negative samples provided, percentage of stimulant- and alcohol-negative samples provided, longest duration of abstinence, retention, and counseling attendance. RESULTS: Submission of stimulant- and alcohol-negative samples was twice as likely for incentive as for usual care group participants (odds ratio, 1.98; 95% confidence interval, 1.42-2.77). Achieving 4 or more, 8 or more, and 12 weeks of continuous abstinence was approximately 3, 9, and 11 times more likely, respectively, for incentive vs usual care participants. Groups did not differ on study retention or counseling attendance. The average cost of prizes was 120 dollars per participant. CONCLUSION: An abstinence incentive approach that paid 120 dollars in prizes per participant effectively increased stimulant abstinence in community-based methadone maintenance treatment clinics.


Subject(s)
Analgesics, Opioid/therapeutic use , Behavior Therapy/economics , Behavior Therapy/methods , Central Nervous System Stimulants/adverse effects , Methadone/therapeutic use , Substance Abuse Treatment Centers/methods , Substance-Related Disorders/rehabilitation , Token Economy , Adult , Alcohol-Related Disorders/rehabilitation , Alcohol-Related Disorders/urine , Central Nervous System Stimulants/urine , Ethanol/urine , Female , Health Care Costs , Humans , Male , Motivation , Opioid-Related Disorders/etiology , Opioid-Related Disorders/rehabilitation , Opioid-Related Disorders/urine , Reinforcement, Psychology , Substance Abuse Detection , Substance-Related Disorders/etiology , Substance-Related Disorders/urine , Treatment Outcome , United States
15.
J Subst Abuse Treat ; 28(1): 57-65, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15723733

ABSTRACT

This paper explores the impact of the adoption of the contingency management approach by the Chemical Dependency Treatment Services of the New York City Health and Hospitals Corporation (HHC). The utilization of this approach grew out of an alliance between NIDA Clinical Trials Network-affiliated clinicians and researchers and a leadership team at the HHC. Interviews and dialogues with administrators, staff, and patients revealed a shared sense that the use of contingency management had: (1) increased patient motivation for treatment and recovery; (2) facilitated therapeutic progress and goal attainment; (3) improved the attitude and morale of many staff members and administrators; and (4) developed a more collegial and affirming relationship not only between patients and staff, but also among staff members.


Subject(s)
Behavior Therapy/methods , Opioid-Related Disorders/rehabilitation , Rehabilitation, Vocational , Reinforcement, Psychology , Attitude of Health Personnel , Health Plan Implementation , Humans , Inservice Training , Methadone/therapeutic use , New York City , Opioid-Related Disorders/psychology , Patient Satisfaction , Substance Abuse Treatment Centers/organization & administration , Substance-Related Disorders/psychology , Substance-Related Disorders/rehabilitation , Treatment Outcome
16.
J Subst Abuse Treat ; 25(4): 241-7, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14693252

ABSTRACT

This paper makes the case that a perspective called "Gradualism" could serve as a foundation for building a therapeutic continuum between the harm reduction and abstinence-oriented treatment worlds. In contrast to other integrationist writers (Denning, 2001; Marlatt, Blume, & Parks, 2001), this paper argues for the incorporation of abstinence into harm reduction approaches. The goal is to build on the strengths of both perspectives while reducing their weaknesses, and examples of each are provided. Lastly, with the frequent occurrence of relapse among addicted patients, building a continuum could also serve to provide a therapeutic "safety net" for those in need.


Subject(s)
Harm Reduction , Psychotherapy/methods , Substance-Related Disorders/rehabilitation , Humans , Models, Psychological
17.
Drug Alcohol Depend ; 69(2): 137-50, 2003 Mar 01.
Article in English | MEDLINE | ID: mdl-12609695

ABSTRACT

The new Kreek-McHugh-Schluger-Kellogg scale ('KMSK scale') is designed to quantify self-exposure to opiates, cocaine, alcohol, and/or tobacco. Each section of the KMSK scale assesses the frequency, amount, and duration of use of a particular substance during the individual's period of greatest consumption. The scale also assesses the mode of use, whether the substance use is current or past, and whether each substance is the substance of choice. The administration time is under 5 min. In an initial validation study of this scale, 100 human subjects were administered the KMSK scale concurrently with the Structured Clinical Interview for DSM-IV (SCID-I DSM-IV version). The sensitivity and specificity were very good for opiates, cocaine, and alcohol use. In addition, the correlations between KMSK scores and the number of SCID-I criteria items met were excellent for opiates and cocaine and good for alcohol use. Nicotine dependence was not assessed in this study as there is no SCID-I nicotine criteria. These preliminary results show that the KMSK scale may have both construct validity similar to that of other established self-report measures and the potential to be an effective screening instrument for the assessment of a lifetime diagnosis of alcohol, opiate, or cocaine dependence.


Subject(s)
Substance-Related Disorders/diagnosis , Adult , Female , Humans , Male , Psychometrics , Reproducibility of Results , Sensitivity and Specificity
18.
J Pers Assess ; 79(1): 73-84, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12227669

ABSTRACT

An analysis of the relationship among the Personality Assessment Inventory (PAI; Morey, 1991, 1996) Drug Problems (DRG) scale scores, the Addiction Severity Index (ASI; McLellan et al., 1992) scores, and urine toxicology reports revealed that the PAI Drug Problem scale scores of 100 substance-using and substance-abusing men and women were distributed in a manner that was in agreement with the guidelines suggested by Morey (1991, 1996) in the PAI manual. There were significant correlations among the PAI DRG scale and the ASI scales related to frequency of use, negative consequences of use, and need and desire for treatment. Overall, higher scores did reflect both more serious involvements with drug use and more serious problems as a consequence of their involvement.


Subject(s)
Methadone/therapeutic use , Opioid-Related Disorders/diagnosis , Opioid-Related Disorders/drug therapy , Personality Inventory , Substance-Related Disorders/diagnosis , Adult , Female , Humans , Male , New York City , Reproducibility of Results , Sensitivity and Specificity , Severity of Illness Index , Statistics, Nonparametric
19.
Am J Med Genet ; 114(4): 429-35, 2002 May 08.
Article in English | MEDLINE | ID: mdl-11992566

ABSTRACT

It has been demonstrated that the opioid peptide dynorphin plays a role in modulating responses to several psychoactive substances including cocaine. Our laboratory and others have found that mRNA levels of dynorphin in the caudate and putamen are elevated after acute or chronic cocaine exposure in rats. Recently, a 68-base pair (bp) repeat polymorphism within the core promoter region of the human prodynorphin gene has been reported to occur in alleles containing one, two, three, or four copies. This repeat contains a putative AP-1 transcription factor binding site; reporter gene constructs with three or four, but not one or two, copies of the tandem repeats were shown to be associated with increases in transcriptional activation in in vitro cellular assays. We hypothesize that this polymorphism may be associated with individual differences in vulnerability to cocaine dependence or abuse. From an ongoing study of the genetics of addiction, 174 subjects were studied, including individuals with a primary diagnosis (DSM-IV criteria) of cocaine dependence (N = 61) or abuse (N = 22), and controls with no history of any substance dependence or abuse (N = 91). We designed primers for polymerase chain reaction (PCR) to amplify sequences of the promoter region of the prodynorphin gene containing the repeat element. The association of alleles containing three or four repeats with cocaine dependence/abuse was examined. With data stratified by ethnic group, pooled relative risk (RR) with Mantel-Haenszel Chi square was calculated: RR = 0.59 (95% confidence interval 0.37-0.95), chi2 (1) = 4.14, P = 0.042. Our results suggest that this allelic variation at the promoter region of the prodynorphin gene (alleles with three or four repeats), which may result in enhanced transcription of the gene, may contribute to relative protection and decrease individual vulnerability to develop cocaine dependence or abuse.


Subject(s)
Cocaine-Related Disorders/genetics , Enkephalins/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Protein Precursors/genetics , Alleles , Base Sequence , Cocaine-Related Disorders/ethnology , DNA , Enkephalins/physiology , Gene Frequency , Humans , Molecular Sequence Data , Protein Precursors/physiology , Repetitive Sequences, Nucleic Acid
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