Susan J. Boyd

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.

Gender Differences in Acute Tobacco Withdrawal: Effects on Subjective, Cognitive, and Physiological Measures

Gender differences in tobacco withdrawal are of considerable clinical importance, but research findings on this topic have been mixed. Methodological variation in samples sizes, experimental design, and measures across studies may explain the inconsistent results. The current study examined whether male (n = 101) and female (n = 102) smokers (> or =15 cigarettes/day) differed in abstinence-induced changes on a battery of self-report measures (withdrawal, affect, craving), cognitive performance tasks (attention, psychomotor performance), and physiological responses (heart rate, blood pressure, brain electroencephalogram). Participants attended 2 counterbalanced laboratory sessions, 1 following 12 hr of abstinence and the other following ad libitum smoking. Results showed that women reported greater abstinence-induced increases in negative affect, withdrawal-related distress, and urge to smoke to relieve withdrawal distress. In contrast, both genders reported similar abstinence-induced changes in positive affect and urge to smoke for pleasure. Men and women exhibited generally similar abstinence-induced changes in physiological and cognitive performance measures. In addition, gender did not moderate the association between withdrawal symptoms and baseline measures of smoking behavior and dependence. Abstinence-induced changes in withdrawal distress mediated the effect of gender on latency until the 1st cigarette of the day at trend levels ( p < .10). These findings suggest that there are qualitative gender differences in the acute tobacco withdrawal syndrome that may underlie gender-specific smoking patterns.

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.

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.

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.

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 questionaire. 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.

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.

The Relationship Between Parental History and Substance Use Severity in Drug Treatment Patients

The authors explored the relationship between the history of parental problematic alcohol and drug use and their adult childrens alcohol and drug use disorders. Subjects were 347 admissions to an outpatient substance abuse program. There was a positive relationship between the number of parents affected by alcohol and/or drug problems and the percentage of probands with co-existing alcohol and drug use disorders for probands with alcohol use disorders but not for those with only drug abuse. Probands with two affected parents had significantly higher alcohol abuse scores and drug, family, and psychiatric composite test scores than those with a negative family history. This preliminary study indicates that the severity of a probands substance use disorder may be influenced by parental substance use history.

Use of a “Microecologic Technique” to Study Crime Around Substance Abuse Treatment Centers

Whether substance abuse treatment centers affect neighborhood crime is hotly debated. Empirical evidence on this issue is lacking because of the difficulty of distinguishing the crime effect of treatment centers in high-crime areas, the inability to make before-and-after comparisons for clinics founded before computerized crime data, and the need for appropriate control sites. The authors present an innovative method (without an actual data analysis) to overcome these challenges. Clinic addresses and crime data are geocoded by street address. Crimes are counted within concentric-circular, 25-meter “buffers” around the clinics. Regression analyses are used to calculate the “crime slope” (β) among the buffers. A negative β indicates more crimes closer to the site. A similar process is used to evaluate crimes around control sites: convenience stores, hospitals, and residential points. This innovative technique provides valid empirical evidence on crime around substance abuse treatment centers.

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).