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PubMed2005

UV light tanning as a type of substance-related disorder.

OBJECTIVE: To better understand the complex motivations involved with UV light (UVL) tanning behavior. DESIGN: Two written instruments, the CAGE (Cut down, Annoyed, Guilty, Eye-opener) Questionnaire, used to screen for alcohol abuse or dependence, and the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for substance-related disorders, were modified to evaluate subjects for a substance-related disorder involving UVL tanning. SETTING: Galveston Island beach. Subjects A total of 145 beach-goers. MAIN OUTCOME MEASURES: Positive findings from the 2 evaluation instruments. RESULTS: Of the 145 subjects, 38 (26%) met the modified CAGE criteria, and 77 (53%) met the modified DSM-IV-TR diagnostic criteria for a substance-related disorder with regard to UVL and related sun tanning. The results from both instruments were significantly associated (P = .03). CONCLUSIONS: Individuals who chronically and repetitively expose themselves to UVL to tan may have a novel type of UVL substance-related disorder.

Adolescent↗
PubMed1993

Carisoprodol as a drug of abuse.

Carisoprodol (available as Soma and in other commercial forms) is a commonly prescribed muscle relaxant. A small group of patients was recently discovered colluding to obtain the drug under false pretenses for the purposes of substance abuse. Animal and human studies have previously shown limited potential for tolerance or abuse, while the evidence for therapeutic efficacy is inadequate. There are two previous case reports of human carisoprodol abuse or dependence, one in which a patient showed signs of a true withdrawal syndrome. A third case involved a fatality linked to carisoprodol abuse. Data from the National Institute on Drug Abuse reveal that overdose and abuse of carisoprodol may be more common than previously suspected. Carisoprodol use should be limited to short-term treatment of acute musculoskeletal conditions involving significant muscle spasm. Suspicions of abuse should be raised by patients requesting the drug by name, "losing" prescriptions, using carisoprodol chronically, or denying the efficacy of less mind-altering alternatives.

Behavior, Addictive↗
PubMed1999

Attenuation of the euphoric effects of cocaine by the dopamine D1/D5 antagonist ecopipam (SCH 39166)

BACKGROUND: The subjective and reinforcing effects of cocaine in humans are associated with the enhancement of endogenous dopamine function in the mesolimbic system. This study examined the role of dopamine D1-like receptors in the behavioral and mood effects of cocaine by evaluating the effects of the selective D1/D5 antagonist ecopipam (SCH 39166) on subjective responses to intravenous cocaine in 11 subjects with cocaine dependence as defined by DSM-IV. METHODS: Subjects were pretreated in a randomized double-blind fashion with either placebo or 10 mg, 25 mg, or 100 mg of ecopipam orally on 4 separate occasions. Two hours later a single intravenous injection of 30 mg of cocaine was administered. Subjective and cardiovascular responses were measured and blood samples for pharmacokinetic evaluation were obtained prior to cocaine dosing and at various times after dosing. RESULTS: The euphoric (P = .004) and stimulating (P = .03) effects of cocaine were attenuated in a dose-dependent manner by ecopipam, while ratings of desire to take cocaine were diminished (P = .02). Ecopipam in combination with cocaine was safe and well tolerated. CONCLUSION: These data indicate a potentially important role for D1-like receptors in the acute mood-altering and rewarding effects of cocaine in humans.

Adult↗
PubMed1999

Naloxone challenge in smokers. Preliminary evidence of an opioid component in nicotine dependence.

BACKGROUND: This study used an opioid antagonist challenge procedure to evaluate the responsivity of the endogenous opioid system in nicotine-dependent individuals, as evidenced by naloxone-induced alterations in both behavioral (withdrawal, craving) and neuroendocrine (cortisol levels) parameters. METHODS: Twenty subjects (9 smokers and 11 nonsmokers) participated in 4 laboratory sessions during which they were challenged with 0, 0.8, 1.6, or 3.2 mg/70 kg of naloxone and then monitored for 1 hour for subjective signs and symptoms of opiate-like withdrawal, nicotine craving, and alterations in cortisol levels. RESULTS: Nicotine-dependent subjects evidenced naloxone dose-dependent increases in withdrawal signs and symptoms. Lower doses of naloxone also produced increases in urges to smoke (craving) and tiredness in smokers. Smokers, when compared with nonsmokers, had lower prenaloxone baseline levels of cortisol and attenuated cortisol release in response to challenge with naloxone. CONCLUSIONS: These results provide preliminary evidence to suggest that long-term exposure to cigarette smoke is associated with alterations in the responsivity of the endogenous opioid system and the hypothalamic-pituitary-adrenal axis that may contribute to the development of nicotine dependence.

Adult↗
PubMed2000

Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance.

BACKGROUND: Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. METHODS: Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). RESULTS: Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. CONCLUSIONS: In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.

Adult↗
PubMed2000

Common genetic vulnerability for pathological gambling and alcohol dependence in men.

BACKGROUND: In comparison with alcohol dependence (AD), relatively little is known about the causes of pathological gambling (PG). Given the high rate of comorbidity between PG and AD, knowledge about the causes of AD may be applied to understanding those of PG. METHODS: Subjects were adult male twin pairs from the Vietnam Era Twin Registry. Lifetime histories of PG and AD were assessed by structured psychiatric telephone interview. The validity of a continuum of PG liability was tested to determine whether the causes of subclinical PG, or problem gambling, are quantitatively or qualitatively distinct from those of DSM-III-R PG disorder. Genetic model-fitting methods were used to quantify the extent to which the genetic and environmental risk for PG could be explained by the risk for AD. RESULTS: Tests of the continuity model of PG were all consistent with the hypothesis that subclinical PG and DSM-III-R PG disorder have many, perhaps all, of the same risk factors and thus differ quantitatively rather than qualitatively. Depending on the PG definition, between 12% and 20% of the genetic variation and between 3% and 8% of the nonshared environmental variation in the risk for PG were accounted for by the risk for AD. CONCLUSIONS: Subclinical PG, or problem gambling, may be a milder form of PG, rather than an etiologically distinct syndrome. Risk for AD accounts for a significant but modest proportion of the genetic and environmental risk for subclinical PG and DSM-III-R PG disorder.

Adult↗
PubMed2001

Marijuana abstinence effects in marijuana smokers maintained in their home environment.

BACKGROUND: Although withdrawal symptoms are commonly reported by persons seeking treatment for marijuana dependence, the validity and clinical significance of a marijuana withdrawal syndrome has not been established. This controlled outpatient study examined the reliability and specificity of the abstinence effects that occur when daily marijuana users abruptly stop smoking marijuana. METHODS: Twelve daily marijuana smokers were assessed on 16 consecutive days during which they smoked marijuana as usual (days 1-5), abstained from smoking marijuana (days 6-8), returned to smoking marijuana (days 9-13), and again abstained from smoking marijuana (days 14-16). RESULTS: An overall measure of withdrawal discomfort increased significantly during the abstinence phases and returned to baseline when marijuana smoking resumed. Craving for marijuana, decreased appetite, sleep difficulty, and weight loss reliably changed across the smoking and abstinence phases. Aggression, anger, irritability, restlessness, and strange dreams increased significantly during one abstinence phase, but not the other. Collateral observers confirmed participant reports of these symptoms. CONCLUSIONS: This study validated several specific effects of marijuana abstinence in heavy marijuana users, and showed they were reliable and clinically significant. These withdrawal effects appear similar in type and magnitude to those observed in studies of nicotine withdrawal.

Adolescent↗
PubMed2003

Early reactions to cannabis predict later dependence.

CONTEXT: While there is a growing literature on the linkages between early subjective responses to nicotine and alcohol and later risks of nicotine or alcohol dependence, to date there has been no study of this issue in relation to cannabis. OBJECTIVE: To examine the extent to which subjective responses to early (prior to the age of 16 years) cannabis use were associated with subsequent cannabis dependence in a birth cohort studied to the age of 21 years. DESIGN: Data on early (prior to the age of 16 years) subjective reactions to cannabis use and subsequent cannabis dependence were gathered over the course of the Christchurch Health and Development Study, a 21-year longitudinal study of a birth cohort of children born in Christchurch, New Zealand. SETTING: General community sample. PARTICIPANTS: Members of a population-based birth cohort (86.5% white, 11.3% New Zealand Maori, and 2.2% Pacific Island). Main Outcome Measure Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition cannabis dependence (for those aged 16-21 years). RESULTS: Of the cohort, 198 (20%) had used cannabis prior to the age of 16 years. Among this high-risk group, rates of dependence were high with 21.7% meeting DSM-IV criteria for cannabis dependence by the age of 21 years. There were clear tendencies for rates of cannabis dependence to increase with increasing reports of positive responses to early cannabis use: those reporting 5 positive responses had odds of cannabis dependence that were 28.5 (95% confidence interval, 6.3-133.8) times higher than those not reporting positive reactions to cannabis. The association held (odds ratio, 23.4; 95% confidence interval, 4.0-135.9) after control for potentially confounding factors including the extent of use of cannabis prior to age 16 years. The extent of early negative reactions to cannabis was unrelated to later cannabis dependence. CONCLUSIONS: Early subjective responses to cannabis are prognostic of later cannabis dependence. These findings may suggest the presence of genetically mediated individual differences in early responsiveness to cannabis. Clinicians should be aware that young people who report positive reactions to early use of cannabis are at increased risks of later cannabis dependence.

Adolescent↗
PubMed2003

Neural response to alcohol stimuli in adolescents with alcohol use disorder.

BACKGROUND: Cue reactivity studies in alcohol-dependent adults have shown atypical physiological, cognitive, and neural responses to alcohol-related stimuli that differ from the responses of light drinkers. Cue reactivity and its neural substrates are unclear in youth. We hypothesized that teens with alcohol use disorder would show greater brain response than nonabusing teens to alcohol images relative to neutral beverage images in limbic and frontal brain regions. METHODS: We tested the hypotheses in a cross-sectional functional magnetic resonance imaging study. Adolescents aged 14 to 17 were recruited from local high schools. Teens with alcohol use disorders (n = 15) and demographically similar infrequent drinkers (n = 15) met strict exclusion criteria (no left-handedness or neurological, other psychiatric, or other substance use disorders). Diagnoses were determined by means of structured and semistructured clinical interviews. Subjects were shown pictures of alcoholic and nonalcoholic beverage advertisements during blood oxygen level-dependent functional magnetic resonance imaging. Self-reports of craving were obtained before and after cue exposure. RESULTS: Teens with alcohol use disorders showed substantially greater brain activation to alcoholic beverage pictures than control youths, predominantly in the left anterior, limbic, and visual system areas (P<.05; cluster threshold, 515 microL). The degree of brain response to the alcohol pictures was highest in youths who consumed more drinks per month and reported greater desires to drink. CONCLUSIONS: These results confirm previous studies by demonstrating an association between the urge to drink alcohol and blood oxygen use in areas of the brain previously linked to reward, desire, positive affect, and episodic recall. This study extends this relationship to adolescents with relatively brief drinking histories using visual alcohol stimuli, and suggests a neural basis for response to alcohol advertisements in youths with drinking problems.

Adolescent↗
PubMed2005

Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil.

BACKGROUND: The pleasant effects of food and alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of mu-opiate receptors with naltrexone reduces the relapse risk among some but not all alcoholic individuals. OBJECTIVE: To test the hypothesis that alcohol craving is pronounced among alcoholic individuals with a high availability of mu-opiate receptors in the brain reward system. DESIGN: Patients and comparison sample. The availability of central mu-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11-labeled carfentanil in the ventral striatum and compared with the severity of alcohol craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). SETTING: Hospitalized care. PARTICIPANTS: Volunteer sample of 25 male alcohol-dependent inpatients assessed after detoxification of whom 12 underwent PET again 5 weeks later. Control group of 10 healthy men. MAIN OUTCOME MEASURES: After 1 to 3 weeks of abstinence, the availability of mu-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in alcoholic patients compared with healthy controls and remained elevated when 12 alcoholic patients had these levels measured 5 weeks later (P<.05 corrected for multiple testing). Higher availability of mu-opiate receptors in this brain area correlated significantly with the intensity of alcohol craving as assessed by the OCDS. CONCLUSIONS: Abstinent alcoholic patients displayed an increase in mu-opiate receptors in the ventral striatum, including the nucleus accumbens, which correlated with the severity of alcohol craving. These findings point to a neuronal correlate of alcohol urges.

Adult↗