Robert C. Sterling

Cannabinoid and opioid interactions: implications for opiate dependence and withdrawal

Withdrawal from opiates, such as heroin or oral narcotics, is characterized by a host of aversive physical and emotional symptoms. High rates of relapse and limited treatment success rates for opiate addiction have prompted a search for new approaches. For many opiate addicts, achieving abstinence may be further complicated by poly-drug use and co-morbid mental disorders. Research over the past decade has shed light on the influence of endocannabinoids (ECs) on the opioid system. Evidence from both animal and clinical studies point toward an interaction between these two systems, and suggest that targeting the EC system may provide novel interventions for managing opiate dependence and withdrawal. This review will summarize the literature surrounding the molecular effects of cannabinoids and opioids on the locus coeruleus-norepinephrine system, a key circuit implicated in the negative sequelae of opiate addiction. A consideration of the trends and effects of marijuana use in those seeking treatment to abstain from opiates in the clinical setting will also be presented. In summary, the present review details how cannabinoid-opioid interactions may inform novel interventions in the management of opiate dependence and withdrawal.

Gender differences and similarities in African-American crack cocaine abusers

Recent interest in womens health and patient-treatment matching has focused attention on gender differences among substance abusers. This article seeks to extend research in this area to African-American crack cocaine abusers. It describes gender differences and similarities in a large sample (652 males and 595 females) of this important group of patients at a publicly funded, inner-city intensive outpatient clinic. As in previous studies on white working-class inpatients, few significant gender differences were found on demographic characteristics or drug use or treatment histories. Moreover, there were few differences in psychiatric symptomatology, and none in treatment participation or retention. In contrast to some reports, we did not find that women entered treatment with higher levels of depression than men. Most statistically significant differences we found were either too small to be of practical importance, or reflected conventional gender differences ( e. g., women were more likely to care for dependents). —J Nerv Ment Dis 183:260-266, 1995

Inpatient Desire to Drink as a Predictor of Relapse to Alcohol Use Following Treatment

Cravings for alcohol are identified as a trigger for relapse, though laboratory studies of cravings produce mixed results in predicting relapse. The objective of this analysis is to assess the usefulness of craving as a predictor of relapse by assessing 218 adult, alcohol-dependent patients admitted to two separate residential addiction treatment programs. Days craving reported in the week prior to discharge predicted alcohol use at three-month follow-up. Admission spirituality, alcohol-refusal self-efficacy, and depression levels differentiated cravers from non-cravers. Patients who crave alcohol in residential treatment may be at higher relapse risk and identified by intake assessments of self-efficacy, depression, and spirituality.

Effectiveness of abstinence-based incentives: interaction with intake stimulant test results.

Intake urinalysis test result (drug positive vs. negative) has been previously identified as a strong predictor of drug abuse treatment outcome, but there is little information about how this prognostic factor may interact with the type of treatment delivered. The authors used data from a multisite study of abstinence incentives for stimulant abusers enrolled in outpatient counseling treatment (N. M. Petry, J. M. Peirce, et al., 2005) to examine this question. The first study urine was used to stratify participants into stimulant negative (n = 306) versus positive (n = 108) subgroups. Abstinence incentives significantly improved retention in those testing negative but not in those testing positive. Findings suggest that stimulant abusers presenting to treatment with a stimulant-negative urine benefit from abstinence incentives, but alternative treatment approaches are needed for those who test stimulant positive at intake.

Serotonin transporter (5-HTT) gene polymorphisms and susceptibility to cocaine dependence among African-American individuals

Studies indicate that the serotonin system, particularly the serotonin transporter (5‐HTT), may modulate the central effects of cocaine. We investigated whether a polymorphism in the 5′ promotor region (5‐HTTLPR) of the 5‐HTT gene confers susceptibility to cocaine dependence. One hundred and ninety‐seven cocaine‐dependent African‐American subjects and 101 controls were studied. Polymerase chain reaction based genotyping of a biallelic repeat polymorphism in the 5′ promotor region yielded 2 alleles containing 484 (S) and 528 bp (L) repeats, respectively. There were no significant differences between controls of European background (n = 40) and African‐American controls (n = 61) in distribution of genotypes (European: LL = 32.5%, LS = 40.0%, SS = 27.5%; African‐American: LL = 27.9%, LS = 57.4%, SS = 14.7%) (χ2= 3.60, df = 2, p = 0.16) or allele frequencies (European: L = 52.5%, S = 47.5%; African‐American: L = 56.6%, S = 43.4%) (χ2= 2.21, df = 1, p = 0.13). When cocaine patients were compared to an ethnically diverse control group (n = 101), frequencies of the L variant (65.0%) were significantly higher while the S variant (35.0%) was less frequent among cocaine patients compared to controls (L = 53.9%, S = 46.1%) (χ2= 6.83, df = 1, p < 0.01). Similarly, there were more cocaine patients with the LL genotype (41.1%) and less with the SS genotype (11.2%) compared to controls (LL = 29.7%, SS = 21.8%) (χ2= 7.43, df = 2, p < 0.05). However, after restricting controls to African‐American individuals only (n = 61), cocaine subjects and controls did not differ significantly with respect to genotype distribution (χ2= 4.24, df = 2, p = 0.12) or allele frequencies (χ2= 2.83, df = 1, p = 0.10). In conclusion, although comparisons with a heterogeneous control group indicated a possible association between allelic variants of 5‐HTTLPR and cocaine dependence among African‐American cocaine subjects, this relationship was not observed when the control group was limited to African‐American people only. Our findings need to be confirmed on larger samples of ethnically matched individuals.

Underreporting of Cocaine Use at Posttreatment Follow-up and the Measurement of Treatment Effectiveness

Substance abusers, especially cocaine abusers, may underreport their substance use in outcome interviews. Follow-up interviews were conducted and urine specimens were obtained on 633 persons 9 months after admission to a 3-month cocaine treatment program. Although 422 (67%) reported no use of cocaine in the past 30 days, 134 of these (32%) had cocaine-positive urines. This group did not differ on most characteristics at intake or follow-up from the 288 with cocaine-negative urines. The amount of treatment received did affect willingness to admit drug use. Of 132 treatment completers who reported no cocaine use at follow-up, 21 (16%) had positive urines. Of 91 early dropouts who also reported no cocaine use, 36 (40%) had positive urines. This differential rate of underreporting had the effect of seriously underrepresenting the effectiveness of treatment completion as compared with little or no treatment.

Impact of cannabis use during stabilization on methadone maintenance treatment.

BACKGROUND AND OBJECTIVES Illicit drug use, particularly of cannabis, is common among opiate-dependent individuals and has the potential to impact treatment in a negative manner. METHODS To examine this, patterns of cannabis use prior to and during methadone maintenance treatment (MMT) were examined to assess possible cannabis-related effects on MMT, particularly during methadone stabilization. Retrospective chart analysis was used to examine outpatient records of patients undergoing MMT (n = 91), focusing specifically on past and present cannabis use and its association with opiate abstinence, methadone dose stabilization, and treatment compliance. RESULTS Objective rates of cannabis use were high during methadone induction, dropping significantly following dose stabilization. History of cannabis use correlated with cannabis use during MMT but did not negatively impact the methadone induction process. Pilot data also suggested that objective ratings of opiate withdrawal decrease in MMT patients using cannabis during stabilization. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE The present findings may point to novel interventions to be employed during treatment for opiate dependence that specifically target cannabinoid-opioid system interactions.

A retrospective case control study of alcohol relapse and spiritual growth.

In the context of an NIAAA/Fetzer Institute-funded study designed to look at the impact of spirituality in an inpatient alcohol treatment, this retrospective case control study investigated whether spiritual growth occurred during an inpatient phase of treatment for alcohol dependence, the degree to which spiritual gains (if noted) would be maintained at follow-up, and whether spiritual growth would be associated with follow-up sobriety. To accomplish this goal, thirty-six individuals who reported relapsing to alcohol at three-month follow-up were compared with thirty-six matched controls who reported abstinence at follow-up. Spiritual development and change was assessed via a set of six measures. Paired t-tests revealed that spiritual growth occurred across all measures during the treatment phase. Repeated measures analysis of variance (ANOVA) indicated that this growth was maintained at three-month follow-up. Two-way repeated measures ANOVA revealed that while non-relapsers maintained spiritual growth over the course of four weeks of treatment and in the three-month period following treatment, renewed alcohol use was associated with decreased spirituality.

Patient Treatment Choice and Compliance: Data from a Substance Abuse Treatment Program

The authors tested the hypothesis that patients (treatment-seeking cocaine-dependent persons) given the opportunity to choose between treatment approaches would do better than patients randomly assigned to the same approaches in treatment retention and 9-month outcome. Subjects were 34 patients who voluntarily chose to enter individual therapy 1 hour per week (IND) and 33 who chose intensive group therapy for 3 hours, 3 times weekly (INT). There were no significant differences between these two groups on demographic, personality, or addiction severity variables or in treatment retention or 9-month outcome. Comparison with samples of 30 patients who had been randomly assigned to IND and 30 to INT did not confirm the hypothesis that patients who chose their treatment would either remain in treatment for longer periods of time or manifest improved 9-month outcomes. The authors raise several motivational issues.

Contribution of limbic norepinephrine to cannabinoid-induced aversion

RationaleThe cannabinoid system has risen to the forefront in the development of novel treatments for a number of pathophysiological processes. However, significant side effects have been observed in clinical trials raising concerns regarding the potential clinical utility of cannabinoid-based agents. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gaging their actions within the central nervous system that may contribute to the expression of unwanted side effects.ObjectivesIn the present study, we investigated whether norepinephrine (NE) in the limbic forebrain is a critical determinant of cannabinoid receptor agonist-induced aversion and anxiety in rats.MethodsAn immunotoxin lesion approach was combined with behavioral analysis using a place conditioning paradigm and the elevated zero maze.ResultsOur results show that the non-selective CB1/CB2 receptor agonist, WIN 55,212-2, produced a significant place aversion in rats. Further, NE in the nucleus accumbens was critical for WIN 55,212-2-induced aversion but did not affect anxiety-like behaviors. Depletion of NE from the bed nucleus of the stria terminalis was ineffective in altering WIN 55,212-2-induced aversion and anxiety.ConclusionsThese results indicate that limbic, specifically accumbal, NE is required for cannabinoid-induced aversion but is not essential to cannabinoid-induced anxiety.