Marc L. Copersino

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.

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.

Reliability and Validity of a Short Form of the Marijuana Craving Questionnaire

BACKGROUND The Marijuana Craving Questionnaire (MCQ) is a valid and reliable, 47-item self-report instrument that assesses marijuana craving along four dimensions: compulsivity, emotionality, expectancy, and purposefulness. For use in research and clinical settings, we constructed a 12-item version of the MCQ by selecting three items from each of the four factors that exhibited the greatest within-factor internal consistency (Cronbachs alpha coefficient). METHODS Adult marijuana users (n=490), who had made at least one serious attempt to quit marijuana use but were not seeking treatment, completed the MCQ-Short Form (MCQ-SF) in a single session. RESULTS Confirmatory factor analysis of the MCQ-SF indicated good fit with the 4-factor MCQ model, and the coefficient of congruence indicated moderate similarity in factor patterns and loadings between the MCQ and MCQ-SF. Homogeneity (unidimensionality and internal consistency) of MCQ-SF factors was also consistent with reliability values obtained in the initial validation of the MCQ. CONCLUSIONS Findings of psychometric fidelity indicate that the MCQ-SF is a reliable and valid measure of the same multidimensional aspects of marijuana craving as the MCQ in marijuana users not seeking treatment.

Rapid Cognitive Screening of Patients with Substance Use Disorders

To date, there has not been a time-efficient and resource-conscious way to identify cognitive impairment in patients with substance use disorders (SUDs). In this study, we assessed the validity, accuracy, and clinical utility of a brief (10-min) screening instrument, the Montreal Cognitive Assessment (MoCA), in identifying cognitive impairment among patients with SUDs. The Neuropsychological Assessment Battery-Screening Module, a 45-min battery with known sensitivity to the mild to moderate deficits observed in patients with SUDs, was used as the reference criterion for determining agreement, rates of correct and incorrect decision classifications, and criterion-related validity for the MoCA. Classification accuracy of the MoCA, based on receiver operating characteristic (ROC) analysis, was strong, with an area under the ROC curve of 0.86, 95% confidence interval [0.75, 0.97]. The MoCA also showed acceptable sensitivity (83.3%) and specificity (72.9%) for the identification of cognitive impairment. Using a cutoff of 25 on the MoCA, the overall agreement was 75.0%; chance-corrected agreement (kappa) was 41.9%. These findings indicate that the MoCA provides a time-efficient and resource-conscious way to identify patients with SUDs and neuropsychological impairment, thus addressing a critical need in the addiction treatment research community.

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.

Attentional Bias Towards Cocaine-Related Stimuli: Relationship to Treatment-Seeking for Cocaine Dependence

Background: Cocaine-dependent individuals demonstrate attentional bias when measured by Stroop color-naming tasks that have been modified to include cocaine-related words. However, the relationship between attentional bias and the treatment-seeking status of cocaine-dependent individuals has never been explored. The purpose of this study was to compare attentional bias towards cocaine-related verbal stimuli between treatment-seeking and nontreatment-seeking cocaine abusers. Methods: We examined performance on a Stroop task modified to include drug-related words in 17 cocaine-dependent treatment-seeking male participants and 20 cocaine-dependent nontreatment-seeking male participants. Results: Although treatment seekers reported less experience with cocaine than nontreatment seekers, they exhibited increased response latency and made more errors when identifying the colors of cocaine-related words, relative to neutral words (p < .05), whereas nontreatment seekers did not. Conclusions: Factors other than a high frequency of cocaine use may contribute to the difference in attentional bias towards cocaine cues between these subgroups of cocaine users.

Neurocognitive Functioning in Recently Abstinent, Cocaine-Abusing Schizophrenic Patients

PURPOSE This report examined a broad range of cognitive functioning in a group of recently abstinent, cocaine-abusing schizophrenic patients (CA + SZ). METHODS Measures of selective and sustained attention, learning and memory, and executive functioning were administered to CA + SZ patients within 72 h of last cocaine use. A comparison group of non-substance-abusing schizophrenic patients (SZ) presenting for inpatient psychiatric treatment were also examined in an identical time frame. We hypothesized that the neurobiological impact of cocaine abuse and acute abstinence would cause CA + SZ to manifest deficits in all domains of cognitive functioning relative to non-abusing SZ patients. RESULTS Results revealed that CA + SZ displayed significant memory impairment relative to their non-abuser SZ counterparts. No group differences, however, were detected on any other neurocognitive measure. CA + SZ were able to selectively process digit strings during the presence and absence of distracting stimuli, sustain attention, and perform executive functions at performance levels equal to their non-abuser SZ counterparts. IMPLICATIONS These results are consistent with many past studies that have found CA + SZ patients to manifest memory impairment but have relatively well preserved functioning in other cognitive domains. The results are discussed in terms of the biological concomitants of cocaine abuse and acute abstinence in schizophrenia.

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.

Effects of Cognitive Impairment on Substance Abuse Treatment Attendance: Predictive Validation of a Brief Cognitive Screening Measure

Background and objectives: Neuropsychological impairment among patients with substance use disorders (SUDs) contributes to poorer treatment processes and outcomes. However, neuropsychological assessment is typically not an aspect of patient evaluation in SUD treatment programs because it is prohibitively time and resource consuming. In a previous study, we examined the concurrent validity, classification accuracy, and clinical utility of a brief screening measure, the Montreal Cognitive Assessment (MoCA), in identifying cognitive impairment among SUD patients. To provide further evidence of criterion-related validity, MoCA classification should optimally predict a clinically relevant behavior or outcome among SUD patients. The purpose of this study was to examine the validity of the MoCA in predicting treatment attendance. Methods: We compared previously collected clinical assessment data on 60 SUD patients receiving treatment in a program of short duration and high intensity to attendance data obtained via medical chart review. Results: Though the proportion of therapy sessions attended did not differ between groups, cognitively impaired subjects were significantly less likely than unimpaired subjects to attend all of their group therapy sessions. Conclusion: These results complement our previous findings by providing further evidence of criterion-related validity of the MoCA in predicting a clinically relevant behavior (i.e., perfect attendance) among SUD patients. Scientific significance: The capacity of the MoCA to predict a clinically relevant behavior provides support for its validity as a brief cognitive screening measure.