Individual and community predictors of maternal smoking in the city of Baltimore: what can be learned from a predominantly minority case controlled study?

This case control study of 1,000 birth certificates examined what individual and community factors predicted maternal smoking in Baltimore, Maryland. Conditional multinomial logistic regression results indicated women who were White were more likely to start smoking at a young age, but as they got older, they were less likely to smoke. Minority women were more likely to start smoking at a later age. Also, White women were more likely to smoke as the rate of poverty increased, while for minority women, smoking was unrelated to whether they lived in higher or lower poverty areas. Medical assistance status, community education level, and crime rate were not found to be related to smoking status.

Use of a 'microecological technique' to study crime incidents around methadone maintenance treatment centers.

AIMS: Concern about crime is a significant barrier to the establishment of methadone treatment centers (MTCs). Methadone maintenance reduces crime among those treated, but the relationship between MTCs and neighborhood crime is unknown. We evaluated crime around MTCs. SETTING: Baltimore City, MD, USA. PARTICIPANTS: We evaluated crime around 13 MTCs and three types of control locations: 13 convenience stores (stores), 13 residential points and 10 general medical hospitals. MEASURES: We collected reports of Part 1 crimes from 1 January 1999 to 31 December 2001 from the Baltimore City Police Department. DESIGN: Crimes and residential point locations were mapped electronically by street address (geocoded), and MTCs, hospitals and stores were mapped by visiting the sites with a global positioning satellite (GPS) locator. Concentric circular 'buffers' were drawn at 25-m intervals up to 300 m around each site. We used Poisson regression to assess the relationship between crime counts (incidents per unit area) and distance from the site. FINDINGS: There was no significant geographic relationship between crime counts and MTCs or hospitals. A significant negative relationship (parameter estimate -0.3127, P < 0.04) existed around stores in the daytime (7 am-7 pm), indicating higher crime counts closer to the stores. We found a significant positive relationship around residential points during daytime (0.5180, P < 0.0001) and at night (0.3303, P < 0.0001), indicating higher crime counts further away. CONCLUSIONS: Methadone treatment centers, in contrast to convenience stores, are not associated geographically with crime.

Sociodemographic characteristics of cannabis smokers and the experience of cannabis withdrawal.

BACKGROUND: Cannabis withdrawal can be a negative reinforcer for relapse, but little is known about its association with demographic characteristics. OBJECTIVES: Evaluate the association of demographic characteristics with the experience of cannabis withdrawal. METHODS: Retrospective self-report of a "serious" cannabis quit attempt without formal treatment in a convenience sample of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52% white, 78% male) with no other current substance use disorder (except tobacco) or chronic health problems. Reasons for quitting, coping strategies to help quit, and 18 specific withdrawal symptoms were assessed by questionnaire. RESULTS: Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed significant associations with age, race, or sex. Women were more likely than men to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99-10.4, p = .05), especially upset stomach. There were few significant demographic associations with coping strategies or reasons for quitting. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This small study suggests that there are few robust associations between demographic characteristics and cannabis withdrawal. Future studies with larger samples are needed. Attention to physical withdrawal symptoms in women may help promote abstinence.

Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients.

BACKGROUND: Cocaine users not seeking treatment have increased regional brain mu-opioid receptor (mOR) binding that correlates with cocaine craving and tendency to relapse. In cocaine-abusing outpatients in treatment, the relationship of mOR binding and treatment outcome is unknown. METHODS: We determined whether regional brain mOR binding before treatment correlates with outcome and compared it with standard clinical predictors of outcome. Twenty-five individuals seeking outpatient treatment for cocaine abuse or dependence (DSM-IV) received up to 12 weeks of cognitive-behavioral therapy and cocaine abstinence reinforcement, whereby each cocaine-free urine was reinforced with vouchers redeemable for goods. Regional brain mOR binding was measured before treatment using positron emission tomography with [¹¹C]]-carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment; and 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology. RESULTS: Elevated mOR binding in the medial frontal and middle frontal gyri before treatment correlated with greater cocaine use during treatment. Elevated mOR binding in the anterior cingulate, medial frontal, middle frontal, middle temporal, and sublobar insular gyri correlated with shorter duration of cocaine abstinence during treatment. Regional mOR binding contributed significant predictive power for treatment outcome beyond that of standard clinical variables such as baseline drug and alcohol use. CONCLUSIONS: Elevated mOR binding in brain regions associated with reward sensitivity is a significant independent predictor of treatment outcome in cocaine-abusing outpatients, suggesting a key role for the brain endogenous opioid system in cocaine addiction.

Signal-averaged electrocardiogram in physically healthy, recently abstinent chronic cocaine users.

OBJECTIVES: : Cocaine use is associated with cardiac arrhythmias. Markers of ventricular late potentials, which may be a precursor to malignant ventricular arrhythmias, can be detected by signal-averaged electrocardiography (SA-ECG) but not by standard ECG. METHODS: : We evaluated SA-ECG parameters in 60 medically screened, physically healthy, recently abstinent cocaine users (53 males, mean [SD] age, 34.0 [4.6] years; 10.1 [6.0] years of use) and 54 nondrug-using controls (21 males, mean [SD] age 28.4 [7.8] years). SA-ECGs were done periodically for ≤12 weeks of monitored abstinence in 25 cocaine users. We analyzed 3 SA-ECG parameters considered markers of ventricular late potentials: duration of filtered QRS complex, duration of low-amplitude potentials during terminal 40 ms of QRS complex (LAS40), and root mean square voltage during terminal 40 ms of QRS complex (RMS40). RESULTS: : Cocaine users differed significantly from controls in filtered QRS complex (118.5 [11.2] ms versus 111.9 [11.4] ms; P = 0.03) but not in LAS40 (28.9 [8.2] ms versus 30.8 [8.3] ms; P = 0.40) or RMS40 (40.0 [19.8] µV versus 30.2 [20.1] µV; P = 0.06) values. The proportion of subjects with abnormal SA-ECG parameters did not differ significantly between male cocaine users and male controls. There were no significant changes over time in either the mean values or proportion of subjects with abnormal values for any SA-ECG parameter. There were significant gender differences among controls but not among cocaine users. CONCLUSION: : These findings suggest that chronic cocaine use is not associated with a higher prevalence of abnormal SA-ECG parameters in physically healthy users.

Brain mu-opioid receptor binding: relationship to relapse to cocaine use after monitored abstinence.

RATIONALE: Cocaine users have increased regional brain mu-opioid receptor (mOR) binding which correlates with cocaine craving. The relationship of mOR binding to relapse is unknown. OBJECTIVE: To evaluate regional brain mOR binding as a predictor of relapse to cocaine use is the objective of the study. MATERIALS AND METHODS: Fifteen nontreatment-seeking, adult cocaine users were housed on a closed research ward for 12 weeks of monitored abstinence and then followed for up to 1 year after discharge. Regional brain mOR binding was measured after 1 and 12 weeks using positron emission tomography (PET) with [11C]carfentanil (a selective mOR agonist). Time to first cocaine use (lapse) and to first two consecutive days of cocaine use (relapse) after discharge was based on self-report and urine toxicology. RESULTS: A shorter interval before relapse was associated with increased mOR binding in frontal and temporal cortical regions at 1 and 12 weeks of abstinence (Ps < 0.001) and with a lesser decrease in binding between 1 and 12 weeks (Ps < 0.0008). There were significant positive correlations between mOR binding at 12 weeks and percent days of cocaine use during first month after relapse (Ps < 0.002). In multiple linear regression analysis, mOR binding contributed significantly to the prediction of time to relapse (R2= 0.79, P < 0.001), even after accounting for clinical variables. CONCLUSIONS: Increased brain mOR binding in frontal and temporal cortical regions is a significant independent predictor of time to relapse to cocaine use, suggesting an important role for the brain endogenous opioid system in cocaine addiction.

Exercise stress testing in recently abstinent chronic cocaine abusers.

We compared treadmill exercise stress testing (EST) in 28 medically screened, chronic cocaine users with the cardiovascular effects of an IV cocaine challenge (25 mg or 50 mg). All subjects had a clinically normal EST and echocardiography (except 2 subjects had septal wall hypokinesis). The EST produced significantly greater increases in heart rate and rate-pressure product than did the cocaine challenges. These findings suggest that EST may not provide additional diagnostic information in medically screened cocaine users. EST may cause more cardiac work (indicated by heart rate and blood pressure) than intravenous cocaine (at the doses in this study).

Longitudinal ECG changes in cocaine users during extended abstinence.

BACKGROUND: Cocaine lengthens electrocardiographic QTc, QRS and PR intervals through blockade of sodium and potassium channels, but changes during withdrawal have not been well studied. METHODS: We recorded weekly electrocardiograms (ECGs) from 25 physically healthy cocaine users (84.0% men, mean [S.D.] age 34.7 [4.1] years, 9.0 [5.2] years of cocaine use, 9.4 [3.5] days of use in the 2 weeks prior to admission) over 3 months of monitored abstinence on a closed ward. Subjects had minimal current use of other drugs. Baseline ECGs were recorded 20.5 h [16.6] after last cocaine use. RESULTS: Baseline QTc interval correlated positively with total amount of cocaine used and amount used per day in the 2 weeks prior to ward admission. There was a significant 10.5 ms [12.9] shortening of QTc interval during the first week of withdrawal, with no further significant changes thereafter. There were no significant changes in PR or QRS intervals. CONCLUSIONS: These findings suggest that cocaine-associated QTc prolongation returns toward normal during the first week of cocaine abstinence.

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users.

RATIONALE: A single 90-mg dose of the cannabinoid CB1 receptor antagonist rimonabant attenuates effects of smoked cannabis in humans. OBJECTIVES: The objective of this study is to evaluate whether repeated daily 40-mg doses of rimonabant can attenuate effects of smoked cannabis to the same extent as a single higher (90 mg) dose. MATERIALS AND METHODS: Forty-two male volunteers received one of three oral drug regimens in a randomized, double blind, parallel group design: (1) 40 mg rimonabant daily for 15 days, (2) placebo for 14 days, then 90 mg rimonabant on day 15, or (3) placebo for 15 days. All participants smoked an active or placebo cannabis cigarette 2 h after medication on days 8 and 15. Subjective effects were measured with visual analog scales and the marijuana-scale of the Addiction Research Center Inventory. RESULTS: Cannabis-induced tachycardia was significantly lower for the 40-mg group on day 8 and for the 40 and 90 mg rimonabant groups on day 15 as compared to placebo. The 40-mg dose significantly decreased peak subjective effects on day 8. Neither the 90-mg nor 40-mg doses significantly decreased peak subjective effects on day 15. Rimonabant treatment did not significantly affect Delta(9)-tetrahydrocannabinnol pharmacokinetics. CONCLUSIONS: Repeated lower daily rimonabant doses (40 mg) attenuated the acute physiological effects of smoked cannabis to a similar degree as a single 90-mg dose; repeated 40-mg doses attenuated subjective effects after 8 but not 15 days.

Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration.

Cocaine is rapidly metabolized to major metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME), and minor metabolites, norcocaine, p-hydroxycocaine, m-hydroxycocaine, p-hydroxybenzoylecgonine (pOHBE), and m-hydroxybenzoylecgonine. This IRB-approved study examined cocaine and metabolite plasma concentrations in 18 healthy humans who provided written informed consent to receive low (75 mg/70 kg) and high (150 mg/70 kg) subcutaneous cocaine hydrochloride doses. Plasma specimens, collected prior to and up to 48 h after dosing, were analyzed by gas chromatography-mass spectrometry (2.5 ng/mL limits of quantification). Cocaine was detected within 5 min, with mean+/-SE peak concentrations of 300.4+/-24.6 ng/mL (low) and 639.1+/-56.8 ng/mL (high) 30-40 min after dosing. BE and EME generally were first detected in plasma 5-15 min post-dose; 2-4 h after dosing, BE and EME reached mean maximum concentrations of 321.3+/-18.4 (low) and 614.7+/-46.0 ng/mL (high) and 47.4+/-3.0 (low) and 124.4+/-18.2 ng/mL (high), respectively. Times of last detection were BE>EME>cocaine. Minor metabolites were detected much less frequently for up to 32 h, with peak concentrations

Quitting among non-treatment-seeking marijuana users: reasons and changes in other substance use.

This study examines the self-reported reasons for quitting marijuana use, changes in other substance use during the quit attempt, and reasons for the resumption of use in 104 non-treatment-seeking adult marijuana smokers. Reasons for quitting were shown to be primarily motivated by concerns about the negative impact of marijuana on health and on self- and social image. The spontaneous quitting of marijuana use is often associated with an increase in the use of legal substances such as alcohol, tobacco, and sleeping aids, but not with the initiation of new substance use. These findings suggest areas for further research on spontaneous recovery from marijuana use.

Cannabis withdrawal among non-treatment-seeking adult cannabis users.

This study investigates the clinical significance of a cannabis withdrawal syndrome in 104 adult, non-treatment-seeking, primarily cannabis users who reported at least one serious attempt to stop using cannabis. Retrospective self-report data were obtained on eighteen potential cannabis withdrawal symptoms derived from the literature, including co-occurrence, time course, and any actions taken to relieve the symptom. Study findings provide evidence for the clinical significance of a cannabis withdrawal syndrome, based on the high prevalence and co-occurrence of multiple symptoms that follow a consistent time course and that prompt action by the subjects to obtain relief, including serving as negative reinforcement for cannabis use.

Effect of rate of administration on subjective and physiological effects of intravenous cocaine in humans.

The rate hypothesis of psychoactive drug action holds that the faster a drug reaches the brain and starts to act, the greater its reinforcing effects and abuse liability. A previous human study using a single cocaine dose confirmed the rate hypothesis for subjective responses, but found no rate effect on cardiovascular responses. We evaluated the rate hypothesis in 17 experienced cocaine users (7 [all men] provided complete data; 6 participated in only 1-2 sessions) by administering IV cocaine at each of three doses (10, 25, 50 mg) and injection durations (10, 30, 60 s) in a double-blind, placebo-controlled, escalating dose design. Heart rate, blood pressure, and positive (e.g., rush, high) and negative (e.g., feel bad, anxious) subjective effects (100-mm visual analogue scales) were measured for 1h after dosing. Peak change from baseline, time to peak, and area under the time-response curve were evaluated with repeated measures mixed linear regression analyses, allowing use of data from all sessions for all subjects, including non-completers. Both dose (mg) and infusion rate (mg/s) significantly influenced most subjective and cardiovascular variables. Analysis of the interaction suggested that dose had a stronger impact than rate. Rate had a stronger influence on positive subjective effects than on negative subjective effects or cardiovascular variables. These findings provide support for the rate hypothesis as it applies to both subjective and cardiovascular effects of IV cocaine administration in humans.

Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving.

BACKGROUND: Cocaine treatment upregulates brain mu-opioid receptors (mOR) in animals. Human data regarding this phenomenon are limited. We previously used positron emission tomography (PET) with [11C]-carfentanil to show increased mOR binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of abstinence. METHODS: Regional brain mOR binding potential (BP) was measured with [11C]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on a research ward and in 16 healthy control subjects. RESULTS: Mu-opioid receptor BP was increased in the frontal, anterior cingulate, and lateral temporal cortex after 1 day of abstinence. Mu-opioid receptor BP remained elevated in the first two regions after 1 week and in the anterior cingulate and anterior frontal cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was positively correlated with self-reported cocaine craving. Mu-opioid receptor BP was significantly correlated with percentage of days with cocaine use and amount of cocaine used per day of use during the 2 weeks before admission and with urine benzoylecgonine concentration at the first PET scan. CONCLUSIONS: These results suggest that chronic cocaine use influences endogenous opioid systems in the human brain and might explain mechanisms of cocaine craving and reinforcement.

Strategies for quitting among non-treatment-seeking marijuana smokers.

This study examines self-reported quitting strategies used by adult, non-treatment-seeking marijuana smokers. Sixty-five subjects rated the use and effectiveness of thirteen strategies on a self-developed instrument, the Marijuana Quit Questionnaire. The strategies clustered into three categories/factors, whether grouped by principal components analysis, mean helpfulness rating, or frequency of endorsement: Change Environment, Seeking Organized/Professional Help, and Social Support. Changing one's environment was rated as most helpful while seeking help from professionals was the least helpful. Clinicians are likely to see marijuana users in their practice and should be proactive in offering assistance, incorporating the strategies reported here into treatment plans for their marijuana-using patients.

Gender differences in indices of opioid dependency and medical comorbidity in a population of hospitalized HIV-infected African-Americans.

We examined gender differences in drug use patterns and in medical presentation among 520 hospitalized, HIV-infected African-Americans. Substance abuse history was self-reported, and medical data were obtained by chart review. Overall, 321 (65%) reported ever having used heroin, with equivalent rates in men and women. Women were more likely to report current use, to have sought treatment, and tended to feel more dependent on heroin than men. Among heroin users, women were more likely to be admitted for conditions related to drug use, rather than AIDS, and to have CD4 counts > 200/mm3. These gender differences in opioid dependency and medical comorbidity may indicate a need for alternative treatment approaches for men and women.