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1.
Drug Alcohol Depend ; 127(1-3): 122-8, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22795689

RESUMO

BACKGROUND: Addiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The µ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR). METHODS: The present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n=336, CA n=503) and European American (OA n=1007, CA n=336) populations. RESULTS: The primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p=0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p=4.53 × 10(-5); n=993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p=8.5 × 10(-7)) (p-values non-FDR corrected). CONCLUSION: The present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.


Assuntos
Negro ou Afro-Americano/genética , Transtornos Relacionados ao Uso de Cocaína/genética , Transtornos Relacionados ao Uso de Opioides/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Opioides delta/genética , População Branca/genética , Estudos de Casos e Controles , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/diagnóstico , Vigilância da População/métodos
2.
Genes Brain Behav ; 11(4): 415-23, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22443215

RESUMO

Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/genética , Encefalinas/genética , Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Precursores de Proteínas/genética , Adolescente , Adulto , Negro ou Afro-Americano/genética , Alelos , Comportamento Aditivo/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , População Branca/genética
3.
J Subst Abuse Treat ; 21(3): 111-7, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11728784

RESUMO

Cocaine addiction affects brain reward centers that have evolved to ensure survival. Cocaine euphoria is intensely pleasurable and results from mesolimbic dopamine (DA) neurotransmission. DA signal-receiving neurons in the nucleus accumbens synthesize endogenous opioids and project to numerous reward regions. Cocaine-induced neuroadaptations, including DA depletion, may underlie craving and hedonic dysregulation. Cue-induced craving is vigorously triggered by conditioned elements of the drug environment and associated with measurable limbic activation. Reduced frontal lobe metabolism in cocaine-addicted individuals could explain important clinical phenomena such as denial and the loss of control over limbic impulses. Cocaine addiction is rapidly progressive and associated with severe medical, psychiatric, and psychosocial consequences. Denial shields addicted individuals from their predicament and must be addressed in treatment. Lacking pharmacological options, clinicians must rely entirely on psychosocial approaches. Treatment principles, including engagement, motivational enhancement, abstinence strategies, and craving reduction are discussed in terms of biological rationales.


Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Psicoterapia/métodos , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/terapia , Cocaína Crack/farmacologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/metabolismo , Humanos , Sistema Límbico/efeitos dos fármacos , Sistema Límbico/metabolismo , Modelos Neurológicos , Recompensa
5.
Adv Alcohol Subst Abuse ; 9(1-2): 9-26, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-1974121

RESUMO

Central stimulants have been abused since their inception and we are currently in the midst of a cocaine epidemic that challenges our resources and capabilities. Through their actions on powerful endogenous reward centers, central stimulants produce intense euphoria that reinforces subsequent usage and eventual dependence. Considerable evidence indicates that the activation of dopamine circuits mediates stimulant reward. With regard to cocaine, it has been hypothesized that depletion of central dopamine leads to craving. Euphoria and craving, the key dynamics of stimulant addiction, may therefore result largely from neurochemical alterations of dopamine systems in the brain's reward center. Progressive deterioration of the stimulant addict involving medical, psychiatric, and psychosocial impairment occurs rapidly, underscoring the addiction potential of these agents. Tolerance, sensitization and withdrawal phenomena are discussed from clinical and neurochemical perspectives.


Assuntos
Estimulantes do Sistema Nervoso Central , Euforia/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Anfetaminas/efeitos adversos , Estimulantes do Sistema Nervoso Central/efeitos adversos , Cocaína/efeitos adversos , Humanos , Metilfenidato/efeitos adversos , Síndrome de Abstinência a Substâncias/etiologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação
8.
Psychiatry Res ; 20(4): 261-4, 1987 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3602212

RESUMO

Thirteen hospitalized cocaine addicts complaining of cocaine craving were given a single dose of bromocriptine, a dopamine agonist, in a randomized, double-blind, placebo-controlled study design. Compared to placebo, bromocriptine caused a significant reduction in craving ratings. These data suggest that bromocriptine may be effective as a new, nonaddictive pharmacological treatment for cocaine addicts and support the notion that functional dopamine depletion occurs with chronic cocaine use. Open trials indicate that low-dose bromocriptine may be useful in cocaine detoxification.


Assuntos
Bromocriptina/administração & dosagem , Cocaína , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Testes Psicológicos , Transtornos Relacionados ao Uso de Substâncias/psicologia
10.
J Subst Abuse Treat ; 4(3-4): 197-207, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3325655

RESUMO

Alcohol and drug addiction are defined in behavioral terms as the preoccupation with, compulsive use of, and relapse to drugs that are descriptive and confirmatory. The basis of addiction may involve neurochemical changes in the brain that distort and redirect the drive states (instincts). Tolerance and dependence may only be incidentally associated with addiction as a result of a nonspecific adaptation by the body to the presence of a drug. The cellular adaptation may be the same in all organs. Addiction to alcohol and drugs may have no specific relationship to tolerance and dependence. Addiction occurs in the absence of observable tolerance and dependence to alcohol and drugs. Alcohol and drug addiction is probably more complex than tolerance and dependence. Addiction is difficult to study because of the variability of behavioral phenomena and the underlying intricacies of the neurosubstrates. Tolerance and dependence are still useful as they are indicators of drug use. It is a misconception that long term chronic use is necessary for tolerance and dependence to develop. Some studies have shown that tolerance can develop within hours and days to a single dose of alcohol or other drugs. Anxiety, depression and insomnia can occur after a single dose of ethanol in humans. These symptoms of withdrawal from the alcohol or drug constitute dependence. Redefining the criteria for addiction tolerance and dependence to alcohol and other drugs may be in order. A neurochemical model may provide a more definitive and uniform basis for considering addiction, tolerance, and dependence to alcohol and drugs.


Assuntos
Química Encefálica , Etanol/farmacologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Tolerância a Medicamentos , Humanos
13.
J Clin Psychiatry ; 47(7): 384-5, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3722137

RESUMO

Hyperprolactinemia and sexual dysfunction occurred in 7 of 10 chronic cocaine users. Two of these 7 patients who underwent rehabilitation for cocaine abuse and developed hyperprolactinemia and decreased libido are described. One patient developed galactorrhea. These adverse effects were reversed by bromocriptine. The pathophysiology of cocaine abuse and the central dopaminergic influence on sexual function are discussed.


Assuntos
Cocaína , Disfunções Sexuais Psicogênicas/etiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Bromocriptina/uso terapêutico , Feminino , Galactorreia/etiologia , Humanos , Hiperprolactinemia/tratamento farmacológico , Hiperprolactinemia/etiologia , Masculino , Disfunções Sexuais Psicogênicas/tratamento farmacológico
14.
Psychiatry Res ; 17(2): 105-9, 1986 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3961028

RESUMO

The persistence of untreated depression was evaluated in 49 severely depressed alcoholics. After 2 weeks of sobriety, 80% of patients with initial major depression by Research Diagnostic Criteria were no longer depressed. These patients improved without antidepressant medications, suggesting the need for a 2-week period of sobriety before psychopharmacotherapy for depression is instituted. Many severe depressions in actively drinking or recently sober alcoholics may represent alcohol-induced organic affective syndromes which, unlike major depressive illness, remit spontaneously with sobriety.


Assuntos
Alcoolismo/diagnóstico , Transtorno Depressivo/diagnóstico , Adulto , Alcoolismo/reabilitação , Clordiazepóxido/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Psicológicos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico
15.
Alcohol Clin Exp Res ; 10(1): 59-60, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3515993

RESUMO

In order to determine the sensitivity of the dexamethasone suppression test (DST) for major depression in alcoholics, we administered this test to 27 alcoholics with major depression. Sixteen of 27 had abnormal DST results, yielding a 59% sensitivity for depression in alcoholics. When combined with previously reported specificity findings of 100%, the DST significantly (p less than 0.001) distinguished depressed from nondepressed alcoholics.


Assuntos
Alcoolismo/complicações , Transtorno Depressivo/complicações , Dexametasona , Hidrocortisona/sangue , Adulto , Idoso , Transtorno Depressivo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Adv Alcohol Subst Abuse ; 6(2): 7-21, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-2886014

RESUMO

This paper reviews certain clinical and neurochemical aspects of cocaine abuse. Once entrenched patterns of addiction have developed, cocaine addicts suffer progressive financial, medical, psychiatric and psychosocial deterioration that results, to some extent, from cocaine-induced neurochemical alterations in the brain. While cocaine produces euphoria through its stimulatory effect on dopamine neurons, several lines of evidence suggest that dopamine depletion occurs after chronic cocaine abuse. The dopamine neurotransmitter system is therefore a natural starting point for understanding the biology of cocaine addiction and selecting suitable adjunctive pharmacological agents. Furthermore, the dopamine depletion hypothesis implies that cocaine is "physically" addictive and provides a biological framework for understanding this disease and refining present therapeutic approaches.


Assuntos
Encéfalo/fisiopatologia , Cocaína , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Antipsicóticos/uso terapêutico , Bromocriptina/uso terapêutico , Cocaína/efeitos adversos , Desipramina/uso terapêutico , Dopamina/fisiologia , Euforia/fisiologia , Humanos , Receptores Dopaminérgicos/fisiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação
17.
J Clin Psychiatry ; 47(1 Suppl): 17-23, 1986 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3510197

RESUMO

Despite the high incidence of substance abuse, it remains a common cause of misdiagnosis. In patients who have abused or who are currently abusing drugs, symptoms of a psychiatric illness may be mimicked by either the drug's presence or absence. The laboratory can aid in making a differential diagnosis and eliminating drugs from active consideration as a cause of psychosis, depression, mania, and personality changes. Treatment planning and prevention of serious medical consequences often rest on the accuracy of the admission drug screen. Testing is widely used to assess improvement in substance abuse in both inpatient and outpatient settings. In occupational settings, testing has been used as an early indicator that a problem exists and as a successful prevention tool. The appropriate use of analytic technology in drug abuse testing requires an understanding of available test methodologies. These include drug screens by thin-layer chromatography, comprehensive testing using enzyme immunoassay, and computer-assisted gas chromatography-mass spectrometry (GC-MS). Testing for specific drugs considered likely causes or precipitants of "psychiatric" complaints is available with enzyme assays, radioimmunoassay, or definitive forensic-quality testing using GC-MS.


Assuntos
Cromatografia/métodos , Imunoensaio/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Alcoolismo/psicologia , Anfetaminas/efeitos adversos , Cromatografia Gasosa , Cromatografia em Camada Fina , Técnicas de Laboratório Clínico , Cocaína/efeitos adversos , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hipnóticos e Sedativos/efeitos adversos , Técnicas Imunoenzimáticas , Dietilamida do Ácido Lisérgico/efeitos adversos , Abuso de Maconha/psicologia , Transtornos Mentais/induzido quimicamente , Transtornos Relacionados ao Uso de Opioides/psicologia , Fenciclidina/efeitos adversos , Radioimunoensaio , Síndrome de Abstinência a Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/psicologia
19.
Am J Psychiatry ; 142(9): 1097-9, 1985 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3927753

RESUMO

The authors administered the thyrotropin-releasing hormone (TRH) test to 17 patients with severe cocaine abuse and without major depression. The results suggest that the test is not specific for major depression when serious cocaine abuse is present.


Assuntos
Cocaína , Transtorno Depressivo/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/complicações , Hormônio Liberador de Tireotropina , Adulto , Transtorno Depressivo/sangue , Transtorno Depressivo/complicações , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Tireotropina/sangue
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