To facilitate effectiveness testing and dissemination of treatments to community based setting, therapist training manuals that are more “community friendly” are needed. The aim of the current project was to create revised versions of individual drug counseling (IDC) and group drug counseling (GDC) treatment manuals for cocaine dependence and to conduct a preliminary study of their effectiveness. After changing the format and context of existing drug counseling manuals to have greater ease of use in the community, draft manuals were given to 23 community-based counselors for their feedback. Final versions were then used in a pilot randomized clinical trial involving 41 cocaine dependent patients who received 3 months of either IDC + GDC or GDC alone treatment. Counselors implemented the new treatment manuals with acceptable levels of adherence and competence. Outcome results indicated that substantial change in drug use was evident, but the amount of abstinence obtained was limited.
Cocaine dependence; drug counseling; randomized trial
This article presents the development of a new 82-item rating scale of
therapist adherence and competence for supportive-expressive (SE) dynamic
psychotherapy for the treatment of cocaine dependence. Sixty- four items
are rated for adherence, appropriateness, and quality of prescribed
interventions. As part of the pilot/training phase of the National
Institute on Drug Abuse Collaborative Cocaine Treatment Study, two
independent expert judges rated 32 audiotapes of SE therapy sessions with
cocaine-dependent patients, 10 tapes of cognitive therapy (CT) sessions,
and 10 tapes of individual drug counseling (IDC) sessions. Reliability was
acceptable for adherence but poor for quality and appropriateness. SE
therapists used more expressive (interpretative) techniques than did either
CT therapists or IDC counselors, and they used more supportive techniques
than did IDC counselors.
The role of therapist characteristics in therapy training was examined for 62 therapists in a multisite psychotherapy outcome study that included cognitive therapy (CT), supportive-expressive (SE) psychodynamic therapy, and individual drug counseling (IDC) for cocaine-dependent patients. Demographic variables and experience and competence ratings prior to training were correlated with measures of change in competence during the training phase. Higher competence ratings before training were associated with greater change in competence for SE and higher average competence for IDC. More years of experience were associated with greater change in competence for CT therapists, but more hours of pre-training supervision in the CT treatment modality were associated with less change.
Psychotherapy Training and Supervision; Therapist Characteristics; Cocaine
Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo.
This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200 mg, and 69 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days.
The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p > 0.79). However, two secondary outcomes showed significant effects by modafinil 200 mg: the maximum number of consecutive non-use days for cocaine (p = 0.02), and a reduction in craving (p = 0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p < 0.02).
These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.
Modafinil; Cocaine-related disorders; Alcoholism; Pharmacotherapy; Risk factors
Buprenorphine is a partial μ-opiate agonist and κ-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence.
Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling.
The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P = .0135 for 8 mg and P < .001 for 16 mg) or benzoylecgonine concentrations (P = .0277 for 8 mg and P = .006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events.
A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use.
Contingency management (CM) treatments are efficacious in treating cocaine abuse. Despite high prevalence rates of alcohol dependence (AD) among individuals with cocaine use disorders, relatively little data are available regarding whether cocaine abusing patients with AD have poorer treatment outcomes in general, or in response to CM treatments in particular, than cocaine abusers without AD. Using data from three randomized trials of CM for cocaine abuse, this study compared cocaine abusers (N = 393) with and without AD in terms of 1) abstinence during treatment and at the Month 9 follow-up, and 2) psychosocial adjustment during the 12-week treatment period and through the follow-up period. Compared to non-AD participants, AD participants had more lifetime years of cocaine and alcohol use, and they had greater severity of alcohol and psychiatric problems. CM was positively and significantly associated with longer durations of substance abstinence, regardless of AD status. Although not significantly associated with primary substance use treatment outcomes, the presence of AD was related to improvement in medical and alcohol-related problems during treatment, and these gains were maintained posttreatment. The results suggest that cocaine abusers benefit equally well from CM treatments, regardless of AD status, and that AD participants are able to offset greater baseline severity in some areas of psychosocial functioning during treatment and maintain these improvements posttreatment.
treatment outcome; contingency management; alcohol dependence; cocaine abuse; cocaine dependence
We investigated the impact of enhancing brief cognitive behavioral therapy with motivational interviewing techniques for cocaine abuse or dependence, using a focused intervention paradigm.
Participants (n=74) who met current criteria for cocaine abuse or dependence were randomized to 3-session cognitive behavioral therapy (CBT) or 3-session enhanced CBT (MET + CBT), which included an initial session of motivational enhancement therapy (MET). Outcome measures included treatment retention, process measures (e.g., commitment to abstinence, satisfaction with treatment), and cocaine use.
Participants who received the MET+CBT intervention attended more drug treatment sessions following the study interventions, reported significantly greater desire for abstinence and expectation of success, and they expected greater difficulty in maintaining abstinence compared to the CBT condition. There were no differences across treatment conditions on cocaine use.
These findings offer mixed support for the addition of MET as an adjunctive approach to CBT for cocaine users. In addition, the study provides evidence for the feasibility of using short-term studies to test the effects of specific treatment components or refinements on measures of therapy process and outcome.
cognitive-behavioral therapy; motivational enhancement therapy; cocaine
We examined the ability of several baseline variables to predict treatment outcome in a pharmacotherapy trial that included 164 participants who were both cocaine- and alcohol-dependent and were selected for a randomized, double-blind, placebo-controlled study. Predictor variables included results from the baseline Addiction Severity Index (ASI), initial Urine Drug Screen results, cocaine and alcohol craving and cocaine and alcohol withdrawal symptoms at the start of treatment. Successful treatment was defined as four continuous weeks of self-reported cocaine abstinence verified by urine drug screens. In respect to demographic characteristics, there were no significant differences between patients who achieved four weeks of abstinence from cocaine and those who did not. Baseline variables that most consistently predicted cocaine abstinence included initial urine drug screen (UDS) results, the initial Cocaine Selective Severity Assessment (CSSA) scores, and initial self-reported cocaine use in past 30 days, whereas cocaine craving, cocaine composite scores, alcohol craving, alcohol withdrawal symptoms, and alcohol composite scores did not. The results of this study suggest that cocaine dependence severity in general, and initial UDS results, the CSSA scores and frequency of recent cocaine use in particular, have a significant impact on treatment outcome in the treatment of cocaine-dependent patients with comorbid alcoholism. Initial UDS results and CSSA scores are very useful predictors of treatment outcome and could be used as stratifying variables in outpatient cocaine and alcohol medication trials.
Although cocaine dependence involves abnormalities in drug-related reward-based decision-making, it is not well understood whether these abnormalities generalize to non-drug-related cues and rewards, and how neural functions underlying reward processing in cocaine abusers relate to treatment outcome.
Twenty cocaine dependent (CD) patients before treatment and 20 matched healthy control (HC) subjects participated in fMRI while performing a Monetary Incentive Delay Task (MIDT). Outcomes through eight weeks were assessed via percent cocaine-negative urine toxicology, self-reported cocaine abstinence, and treatment retention.
Amongst the whole sample, anticipation of working for monetary reward (i.e., reward anticipation) was associated with activation in the ventral striatum (VS), medial frontal gyrus, thalamus, right subcallosal gyrus, right insula, and left amygdala. CD as compared with HC participants exhibited greater activation during notification of rewarding outcome (i.e., reward receipt) in left and right VS, right caudate, and right insula. In CD participants during reward anticipation, activation in left and right thalamus and right caudate correlated negatively with percent cocaine-negative urine toxicology, activation in thalamus bilaterally correlated negatively with self-reported abstinence measures, and activation in left amygdala and parahippocampal gyrus correlated negatively with treatment retention. During reward notification, activation in right thalamus, right VS and left culmen correlated negatively with abstinence and with urine toxicology.
These findings suggest that in treatment-seeking CD participants, cortico-limbic reward circuitry is relatively over-activated during MIDT performance and specific regional activations related to reward processing may predict aspects of treatment outcome and represent important targets for treatment development in CD.
Cocaine Dependence; Reward Circuitry; Monetary Incentive Delay Task; Anticipation; fMRI; Treatment Outcome
The NIDA Collaborative Cocaine Treatment Study yielded different efficacies for different psychosocial treatments for cocaine dependence. However, substantial heterogeneity of patient outcomes was evident. Longitudinal data analysis techniques can be helpful in examining differential effects of psychosocial interventions on specific subpopulations of patients.
Overall drug and cocaine use of 346 patients diagnosed with DSM-IV cocaine dependence and treated with one of four psychosocial interventions were assessed monthly during 6-month treatment. Growth mixture models were used to identify patient subgroups based on typical patterns of change in substance use during treatment and to evaluate differential treatment effects within these subgroups.
Three patient subgroups following different change patterns in cocaine and overall drug use were identified irrespective of the treatment type: (a) those with moderate baseline severity of drug use and very rapid reduction of drug use during treatment, (b) those with moderate baseline severity of drug use and moderate reduction of drug use during treatment, and (c) those with severe levels of baseline drug use with moderate reduction of drug use during treatment. Patient baseline characteristics enabled discrimination between these subgroups. Individual drug counseling was most efficacious among those patients with moderate baseline severity and moderate treatment response. There were no differential treatment effects in the two other patient subgroups.
The population of treatment-seeking cocaine dependent individuals is heterogeneous. Research on patient subgroups with different change patterns revealed its potential to enable classifications of patients that indicate which treatment is most effective for which type of patient.
Cocaine Dependence; Psychosocial Treatment; Differential Treatment Effects; Patterns of Change; Growth Mixture Modeling
Cocaine dependence is associated with high relapse rates but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central Brain Derived Neurotrophic Factor (BDNF) in cocaine seeking, we examined whether serum BDNF is altered in abstinent, early recovering, cocaine-dependent individuals and if it is predictive of subsequent relapse risk.
Serum samples were collected across three consecutive mornings from 35 treatment-engaged, 3 week abstinent cocaine-dependent inpatients (17M/18F) and 34 demographically matched hospitalized healthy control participants (17M/17F). Cocaine dependent individuals were prospectively followed on days 14, 30 and 90 post-treatment discharge to assess cocaine relapse outcomes. Time to cocaine relapse, number of days of cocaine use (frequency), and amount of cocaine use (quantity) were the main outcome measures.
High correlations in serum BDNF across days indicated reliable and stable serum BDNF measurements. Significantly higher mean serum BDNF levels were observed for the cocaine-dependent patients compared to healthy control participants (p<.001). Higher serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard ratio: HR: 1.09, p<.05), greater number of days (p<.05) and higher total amounts of cocaine used (p = .05).
High serum BDNF levels in recovering cocaine-dependent individuals are predictive of future cocaine relapse outcomes and may represent a clinically relevant marker of relapse risk. These data suggest that serum BDNF levels may provide an indication of relapse risk during early recovery from cocaine dependence.
BDNF; cocaine dependence; cocaine relapse; treatment outcome
Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users.
To compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies—cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)—in reducing cocaine use.
Randomized, placebo-controlled, double-masked (for medication condition), factorial (2×2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT.
A community-based outpatient substance abuse treatment program.
A total of 121 individuals meeting the criteria for current cocaine dependence.
Patients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks.
Main Outcome Measures
Random regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens.
Participants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT (P<.01 for both). Findings were consistent across all study samples (eg, intention to treat, treatment initiators, and treatment completers). Benefits of disulfiram use and CBT were most pronounced for participants who were not alcohol dependent at baseline or who fully abstained from drinking alcohol during treatment. Adverse effects experienced by participants who received disulfiram were mild and were not considerably different from those experienced by participants who received placebo.
Disulfiram and CBT are effective therapies for general populations of cocaine-dependent individuals. Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use.
We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p = 0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p = 0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence.
Buprenorphine; Cocaine; Heroin; Dual dependence; Psychotherapy
Cocaine dependence is associated with white matter impairments that may compromise cognitive function and hence drug users’ abilities to engage in and benefit from treatment. The main aim of this study was to assess whether white matter integrity correlates with treatment outcome measures in cocaine dependence. Diffusion tensor imaging (DTI) was used to assess the white matter (WM) of 16 treatment-seeking cocaine-dependent patients before 8 weeks of therapy. The measures for treatment outcome were longest self-reported duration of continuous cocaine abstinence, percent of urine screens negative for cocaine, and duration (weeks) of treatment retention. Correlations between treatment outcome measures and DTI parameters (fractional anisotropy (FA), longitudinal eigenvalue (λ1), perpendicular eigenvalue (λT), and mean diffusivity (MD)) were analyzed. Longest self-reported abstinence from cocaine and percent of cocaine negative urine samples during treatment positively correlated with FA values and negatively correlated with λ1, λT, and MD values across extensive brain regions including the corpus callosum, frontal, parietal, temporal, and occipital lobes, and cerebellum. The findings of an association between better WM integrity at treatment onset and longer abstinence suggest that strategies for improving WM integrity warrant consideration in developing new interventions for cocaine dependence.
DTI; Brain; neuroimaging; cognitive behavioral therapy; substance use disorder; addiction
Cocaine dependence is associated with white matter impairments that may compromise cognitive function and hence drug users' abilities to engage in and benefit from treatment. The main aim of this study was to assess whether white matter integrity correlates with treatment outcome measures in cocaine dependence. Diffusion tensor imaging (DTI) was used to assess the white matter (WM) of 16 treatment-seeking cocaine-dependent patients before 8 weeks of therapy. The measures for treatment outcome were longest self-reported duration of continuous cocaine abstinence, percent of urine screens negative for cocaine, and duration (weeks) of treatment retention. Correlations between treatment outcome measures and DTI parameters (fractional anisotropy (FA), longitudinal eigenvalue (λ1), perpendicular eigenvalue (λT), and mean diffusivity (MD)) were analyzed. Longest self-reported abstinence from cocaine and percent of cocaine-negative urine samples during treatment positively correlated with FA values and negatively correlated with λ1, λT, and MD values across extensive brain regions including the corpus callosum, frontal, parietal, temporal, and occipital lobes, and cerebellum. The findings of an association between better WM integrity at treatment onset and longer abstinence suggest that strategies for improving WM integrity warrant consideration in developing new interventions for cocaine dependence.
DTI; brain; neuroimaging; cognitive behavioral therapy; substance use disorder; addiction; Addiction & Substance Abuse; Psychiatry & Behavioral Sciences; Biological Psychiatry; Imaging; Clinical or Preclinical; Diffusion tensor imaging; Behavioral therapy
Concurrent alcohol dependence (AD) among polysubstance abusers has been associated with negative consequences, although it may not necessarily lead to poor treatment outcomes. One of the most efficacious treatments for cocaine abuse is contingency management (CM), but little research has explored the impact of AD on abstinence outcomes, particularly among patients in methadone maintenance. Using data from three trials of CM for cocaine use, we compared baseline characteristics and post-treatment and follow-up cocaine outcomes between methadone maintained, cocaine dependent patients (N=193) with and without concurrent AD, randomized to standard care (SC) with or without CM. Patients with and without concurrent AD had similar baseline characteristics, with the exception that AD patients reported more alcohol use. AD patients achieved longer durations of cocaine abstinence and were more likely to submit a cocaine negative sample at follow-up than non-AD patients. Patients randomized to CM achieved better outcomes than those randomized to SC, but there was no interaction between treatment condition and AD status. These findings suggest that cocaine using methadone patients with AD achieve greater cocaine abstinence than their non-AD counterparts and should not be necessarily viewed as more difficult to treat.
alcohol dependence; treatment outcomes; contingency management; cocaine dependence; methadone
There is a lack of psychotherapeutic trials of treatments of comorbid depression in cancer patients. Our study determines the efficacy of a manualized short-term psychodynamic psychotherapy and predictors of outcome by personality and quality of the therapeutic relationship.
Eligible breast cancer patients with comorbid depression are assigned to short-term psychodynamic psychotherapy (up to 20 + 5 sessions) or to treatment as usual (augmented by recommendation for counseling center and physician information). We plan to recruit a total of 180 patients (90 per arm) in two centers. Assessments are conducted pretreatment, after 6 (treatment termination) and 12 months (follow-up). The primary outcome measures are reduction of the depression score in the Hospital Anxiety and Depression Scale and remission of depression as assessed by means of the Structured Clinical Interview for DSM IV Disorders by independent, blinded assessors at treatment termination. Secondary outcomes refer to quality of life.
We investigate the efficacy of short-term psychodynamic psychotherapy in acute care and we aim to identify predictors for acceptance and success of treatment.
Breast cancer; Depression; Short-term psychodynamic psychotherapy; Personality; Helping alliance; Quality of life
Alpha synuclein is increased in dopamine neurons of cocaine abusers and in rats whose alcohol preference is inbred. Recent studies have shown increased alpha-synuclein protein expression in serum of alcoholic patients that is linked with severity of alcohol craving. The aim of this study was to analyze the serum levels of alpha synuclein in healthy subjects and in recently abstinent cocaine abusers. Alpha synuclein protein expression was measured by enzyme-linked immunosorbent assay in serum specimens obtained from 38 recently abstinent cocaine dependent patients and 14 control subjects. The presence of cocaine dependence disorder was based on the Structured Clinical Interview (DSM-IV). Drug severity was assessed by the Addiction Severity Index ratings and composite measures. Scores of the intensity and frequency of cocaine craving episodes were obtained from the Minnesota Cocaine Craving Questionnaire. The serum concentrations of alpha synuclein in cocaine dependent patients were significantly higher as compared with age-matched drug-free controls (p < 0.001). Alpha synuclein levels in blood were significantly correlated with the intensity (r = 0.60, p < 0.001) and frequency (r = 0.64. p < 0.001) of cocaine craving and with thirty days of cocaine use in the prior month before entry to treatment (r = 0.56, p < 0.005). However, there was no correlation between the serum protein levels of alpha synuclein and age in either group. This report is the first demonstration of altered alpha synuclein levels in peripheral blood from cocaine abusers. These data agree with previous reports in postmortem brain of cocaine abusers and provide support for an association between alpha synuclein and cocaine dependence.
Cocaine; serum; dopamine; craving; synuclein
We prospectively examined the gender-specific effects of childhood trauma on cocaine relapse outcomes in an inpatient sample of treatment engaged cocaine dependent adults. Cocaine dependent men (n = 70) and women (n = 54) participating in inpatient treatment for cocaine dependence were assessed on severity of childhood trauma and followed for 90 days after discharge from treatment. Greater severity of childhood emotional abuse was associated with an increased risk of relapse in women. Severity of emotional abuse, sexual abuse, and overall childhood trauma was associated with the number of days cocaine was used during follow-up in women, as was the association of severity of physical abuse and overall childhood trauma with the average amount of cocaine used per occasion. No associations between childhood trauma and cocaine relapse outcomes were found in men. These findings demonstrate that childhood trauma increases the likelihood of cocaine relapse and drug use escalation after initial relapse in women but not in men. Comprehensive assessments of childhood trauma and specialized treatments that address trauma-related pathophysiology could be of benefit in improving cocaine treatment outcomes in women.
childhood trauma; cocaine dependence; relapse; treatment outcome; gender
Relapse to drug use after a period of abstinence is a persistent problem in the treatment of cocaine dependence. Physical activity decreases cocaine self-administration in laboratory animals and is associated with a positive prognosis in human substance-abusing populations. The purpose of this study was to examine the effects of long-term access to a running wheel on drug-primed and cue-induced reinstatement of cocaine-seeking behavior in male and female rats.
Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) and exercising (access to wheel) groups for the duration of the study. After 6 weeks, rats were implanted with intravenous catheters and trained to self-administer cocaine for 14 days. After training, saline was substituted for cocaine and responding was allowed to extinguish, after which cocaine-primed reinstatement was examined in both groups. Following this test, cocaine self-administration was re-established in both groups for a 5-day period. Next, a second period of abstinence occurred in which both cocaine and the cocaine-associated cues were withheld. After 5 days of abstinence, cue-induced reinstatement was examined in both groups.
Sedentary and exercising rats exhibited similar levels of cocaine self-administration, but exercising rats responded less than sedentary rats during extinction. In tests of cocaine-primed and cue-induced reinstatement, exercising rats responded less than sedentary rats, and this effect was apparent in both males and females.
These data indicate that long-term access to a running wheel decreases drug-primed and cue-induced reinstatement, and that physical activity may be effective at preventing relapse in substance-abusing populations.
cocaine; exercise; extinction; reinstatement; self-administration; sex differences
Cocaine abuse and dependence continue to be widespread. Currently there are no pharmacotherapies shown to be effective in the treatment of cocaine dependence.
A 33-week outpatient clinical trial of fluoxetine (60 mg/day, p.o.) for cocaine dependence was conducted that incorporated abstinence-contingent voucher incentives. Participants (n=145) were both cocaine and opioid dependent and treated with methadone. A stratified randomization procedure assigned subjects to one of four conditions: fluoxetine plus voucher incentives (FV), placebo plus voucher incentives (PV), fluoxetine without vouchers (F), and placebo without vouchers (P). Dosing of fluoxetine/placebo was double blind. Primary outcomes were treatment retention and cocaine use based on thrice-weekly urine testing.
The PV group had the longest treatment retention (mean of 165 days) and lowest probability of cocaine use. The adjusted predicted probabilities of cocaine use were: 65% in the P group, 60% in the F group, 56% in the FV group, and 31% in the PV group.
Fluoxetine was not efficacious in reducing cocaine use in patients dually dependent on cocaine and opioids.
Cocaine; Contingency management; Fluoxetine; Methadone
Individuals who use cocaine report a variety of neuropsychiatric symptoms that are yet to be adequately targeted with treatment modalities. To address this problem requires an understanding of these symptoms and their neurobiological origins. Our paper reviewed the existing data on the neuropsychiatic implications of cocaine. We conducted a Medline search from 1984-2004 using terms, such as "cocaine", "cocaine addiction", "cocaine abuse", "cocaine neuropsychiatry" and "dual diagnosis". The search produced additional reference materials that were used in this review, although we focused on data that have likely clinical implications. The literature evidence suggested that, whereas acute cocaine overdose is potentially fatal, the ingestion of mild-to-moderate doses could result in fatal or nonfatal neuropsychiatric events. Also, chronic cocaine use may be associated with deficits in neurocognition, brain perfusion and brain activation patterns. Some of these deficits were unresolved with periods of abstinence ranging from 3-200 days. Taken together, these studies suggest the need for further investigations to fully characterize the neurobiological substrates of cocaine use disorders (CUDs) with the future possibility of more efficient treatment modalities.
Chronic exposure to cocaine is associated with neuroadaptions in stress and reward circuits that may increase susceptibility to relapse. We examined whether there are alterations in stress response and craving in abstinent cocaine-dependent individuals compared with a demographically matched group of non-addicted socially drinking community controls. Forty treatment-engaged abstinent cocaine patients (17F/23M) and 40 controls (19F/21M) were exposed to a brief 5 min guided imagery of individually calibrated stressful situations, personal drug/alcohol-related situation and a neutral-relaxing situation, one imagery per session, presented in random order. Craving, anxiety, emotion rating scales, and physiological measures were assessed. Cocaine patients reported significantly higher and more persistent stress- and cue-induced drug/alcohol craving, negative emotions, and physiological responses compared with social drinkers. In cocaine patients, stress- and cue-induced drug craving was accompanied by increased anger, fear, sadness, heart rate, and SBP. Controls reported minimal stress-induced craving and only increases in anxiety and SBP during stress exposure. Cue-induced alcohol craving was accompanied only by an increase in relaxed state. Females reported increased stress-induced anxiety and sadness compared with males, while males were emotionally and physiologically more reactive in the cue condition. These findings are the first to document functional alterations in stress- and reward-related affect and physiology in recently abstinent cocaine patients that is marked by an enhanced sensitivity to stress- and drug-related cue exposure. These data suggest that recovery from chronic cocaine abuse could be hampered by a hyper-responsive stress- and drug-craving state that increases cocaine relapse susceptibility.
cocaine abuse; stress; drug cues; emotion; gender; craving
Cocaine use is common in opioid dependent HIV-infected patients but its impact on treatment outcomes in these patients receiving buprenorphine/naloxone is not known.
We conducted a prospective study in 299 patients receiving buprenorphine/naloxone who provided baseline cocaine data and a subset of 266 patients who remained in treatment for greater than or equal to one quarter. Assessments were conducted at baseline and quarterly for one year. We evaluated the association between baseline and in-treatment cocaine use on buprenorphine/naloxone retention, illicit opioid use, antiretroviral adherence, CD4 counts, HIV RNA, and risk behaviors.
Sixty-six percent (197/299) of patients reported baseline cocaine use and 65% (173/266) of patients with follow-up data reported in-treatment cocaine use. Baseline and in-treatment cocaine use did not impact buprenorphine/naloxone retention, antiretroviral adherence, CD4 lymphocytes, or HIV risk behaviors. However, baseline cocaine use was associated with a 14.8 (95% CI=9.0–24.2) times greater likelihood of subsequent cocaine use (95% CI=9.0 – 24.2), a 1.4 (95% CI=1.02 – 2.00) times greater likelihood of subsequent opioid use, and higher Log10 HIV RNA (p≤ .016) over time. In-treatment cocaine use was associated with a 1.4 (95% CI=1.01–2.00) times greater likelihood of concurrent opioid use.
Given cocaine use negatively impacts opioid and HIV treatment outcomes, interventions to address cocaine use in HIV-infected patients receiving buprenorphine/naloxone treatment are warranted.
Cocaine; HIV; Buprenorphine; heroin dependence; opioid-related disorders
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.
We determined whether regional brain mOR binding before treatment correlates with outcome and compared it to 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 (PET) with [11C] carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment, 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology.
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 sub-lobar 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.
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.
cocaine; mu-opioid receptor; PET; treatment; addiction; dependence