Association between psychiatric symptoms and craving in methamphetamine users

This study examined the differences in psychiatric symptoms between adult methamphetamine users (n = 46) and control subjects (n = 31), the relationship between psychiatric symptoms and the intensity of methamphetamine craving, and whether psychiatric symptoms were correlated to methamphetamine drug-usage variables (ie, length of abstinence, frequency, duration, and lifetime grams). We found that depressive symptoms on the Center for Epidemiology Studies-Depression (CES-D) and many other psychiatric symptoms on the Symptom Checklist-90 (SCL-90) significantly correlated with craving methamphetamine on the visual analog scale (VAS) for craving. Methamphetamine users had significantly more depressive symptoms (on CES-D) and psychotic symptoms (on SCL-90) compared to controls. There were no significant correlations between psychiatric symptoms and methamphetamine-usage variables. This study provides the first evidence to suggest that depressive symptoms (on CES-D) and psychiatric symptoms (on SCL-90) are strongly associated with the intensity of craving (on VAS) for the drug in methamphetamine users. However, the methamphetamine usage variables had no relationship with psychiatric symptoms. Therefore, methamphetamine users, regardless of their usage patterns, may benefit from treatment of their psychiatric symptoms in order to minimize craving and subsequent relapse to drug use.     

The nature, time course and severity of methamphetamine withdrawal

AIMS: To characterize the natural history of methamphetamine withdrawal during the first 3 weeks of abstinence. DESIGN: Cross-sectional study with comparison group. Setting A substance use treatment facility in Chiang Mai Province, Thailand. PARTICIPANTS: The sample comprised 21 in-patients undergoing treatment for methamphetamine dependence. Nine age- and sex-matched non-dependent individuals provided comparison data. MEASUREMENTS: Instruments including: the Amphetamine Withdrawal Questionnaire, a modified version of the Cocaine Selective Severity Assessment, Clinical Global Impression scale and the St Mary's Hospital Sleep Questionnaire were completed daily for the first 3 weeks of abstinence. FINDINGS: Methamphetamine withdrawal severity declined from a high initial peak within 24 hours of the last use of amphetamines reducing to near control levels by the end of the first week of abstinence (the acute phase). The acute phase of amphetamine withdrawal was characterized by increased sleeping and eating, a cluster of depression-related symptoms and less severely, anxiety and craving-related symptoms. Following the acute withdrawal phase most withdrawal symptoms remained stable and at low levels for the remaining 2 weeks of abstinence. CONCLUSIONS: This study has provided evidence of a methamphetamine withdrawal syndrome that can be categorized into two phases, the acute phase lasting 7-10 days during which overall symptom severity declined in a linear pattern from a high initial peak, and a subacute phase lasting at least a further 2 weeks.     

An examination of drug craving over time in abstinent methamphetamine users

Craving for addictive drugs may predict relapse in abstinent addicts. To assess relationships between craving and use, we examined changes in craving for methamphetamine (MA) in a sample of 865 outpatients in a multisite 16-week MA-treatment study. Craving was assessed on a 0-100 scale, and MA use was assessed by self-report and confirmed by urinalysis. We hypothesized that the magnitude of craving would decline (decay) with increased time of abstinence, and that decay would be greater for more frequent MA users, and greater for intravenous (IV) users and smokers as compared to those who used MA intranasally. Craving declined significantly as the number of weeks of consecutive abstinence increased. Rate of decay was greater for IV users and smokers as compared to both intranasal users and oral users, but not for more frequent users of MA. Rate of decay was independent of age, gender, and race/ethnicity. The trajectory to 0 (no) craving was 1 week shorter for females than males because females had significantly lower pretreatment craving scores compared to males. This study confirms that the sooner MA-dependent people are able to quit using and the longer that they are able to stay abstinent, the more likely it is that their craving for MA will decrease over time.     

Prolactin serum levels during alcohol withdrawal are associated with the severity of alcohol dependence and withdrawal symptoms

Background: Prolactin serum levels have been described to be elevated during alcohol withdrawal in alcohol‐dependent patients and normalize during abstinence. Alterations in prolactin levels may reflect disturbances of dopaminergic neurotransmission which is of crucial importance for alcohol‐seeking behavior. Methods: In this longitudinal observational study, we investigated prolactin serum levels in 99 male patients during the first 14 days of alcohol withdrawal and early abstinence and in 43 healthy controls. To assess the severity of alcohol dependence, the extent of withdrawal symptoms, craving, depressive symptoms, and anxiety, we employed a structured interview including psychologic measurements. Results: Prolactin serum levels were elevated during the whole study period in alcohol‐dependent patients compared to the healthy control group. Prolactin levels at admission (first day of alcohol withdrawal) were associated with the severity of alcohol withdrawal (CIWA‐Ar) and of alcohol dependence (SESA) but not with the other assessed psychologic parameters. Conclusions: The presented findings confirm that prolactin is significantly elevated in alcohol‐dependent patients during alcohol withdrawal and early abstinence, not showing a rapid decline after cessation of drinking. The association with the severity of withdrawal and dependence may reflect at least partially the individual alterations in the dopaminergic and glutamatergic pathways.     

Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial

Aims Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double‐blind, placebo‐controlled out‐patient trial tested topiramate for treating methamphetamine addiction. Design Participants (n = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 50 mg/day to the target maintenance of 200 mg/day in weeks 6–12 (tapered in week 13). Medication was combined with weekly brief behavioral compliance enhancement treatment. Setting The trial was conducted at eight medical centers in the United States. Participants One hundred and forty methamphetamine‐dependent adults took part in the trial. Measurements The primary outcome was abstinence from methamphetamine during weeks 6–12. Secondary outcomes included use reduction versus baseline, as well as psychosocial variables. Findings In the intent‐to‐treat analysis, topiramate did not increase abstinence from methamphetamine during weeks 6–12. For secondary outcomes, topiramate reduced weekly median urine methamphetamine levels and observer‐rated severity of dependence scores significantly. Subjects with negative urine before randomization (n = 26) had significantly greater abstinence on topiramate versus placebo during study weeks 6–12. Topiramate was safe and well tolerated. Conclusions Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent.     

Chronic methamphetamine psychosis after long-term abstinence in Japanese incarcerated patients

Eighty female incarcerated subjects who maintained a long-term methamphetamine (Meth) abstinence, but manifested psychosis, were examined for correlations among symptom severity premorbid diathesis, recurrence, and adverse effects of pharmacotherapy. Baseline symptoms were assessed with a 24-item version of the Brief Psychiatric Rating Scale (BPRS) prior to, and 2 weeks after, the commencement of pharmacotherapy. Fifty-four subjects who had abused volatile solvents in their teenage years commenced Meth abuse at a significantly lower age than the rest of the subjects (18.4 vs. 22.5 years old, p < .001). Twenty-nine patients who had attempted suicide in their lives suffered from premorbid psychiatric disorders significantly more often than those who had never attempted suicide (odds ratio = 8.6, 95% confidence interval [CI]= 2.6-27.8, p < .001). Twenty subjects who manifested spontaneous recurrence had a significantly longer abstinence period (17.5 vs. 12.1 months, p = .049), but suffered from premorbid psychiatric disorders significantly less often (odds ratio = .12, 95% CI = .02- .99, p = .031) than those who manifested nonrecurrent-protracted psychosis. Subjects who eventually suffered from extrapyramidal symptoms (EPS) following pharmacotherapy had higher total BPRS scores at the baseline assessment. The present study provides evidence that a subpopulation of Meth abusers suffered from chronic Meth psychosis in long-term abstinence, and also highlights the involvement of affective symptoms in its severity.     

Predictors of Treatment Outcome in Outpatient Cocaine and Alcohol Dependence Treatment

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.     

Effect of pre-treatment with nicotine patch on withdrawal symptoms and abstinence rates in smokers subsequently quitting with the nicotine patch: a randomized controlled trial

Aims To determine whether 2‐week pre‐treatment with transdermal nicotine influences withdrawal symptoms or success rate of subsequent smoking cessation using nicotine patches. Design Randomized controlled trial. Setting Smoking cessation clinic. Participants Healthy smokers (n = 200, 45% female) were allocated randomly to either active nicotine‐patch (AP, 15 mg daily, n = 100) or placebo‐patch (PP, n = 100) pre‐treatment. Baseline characteristics were well balanced except for daily cigarette consumption: mean (± SD) 23.1 (8) and 26.4 (11) for AP and PP groups, respectively (P = 0.021). Intervention At the screening visit (? 2 weeks) subjects were counselled and started pre‐treatment with daily patches (AP or PP). From the quit date (week 0) onwards all subjects received active nicotine patches for 12 weeks (15 mg daily for 8 weeks, 10 and 5 mg daily for 2 weeks each) and counselling. Measurements Follow‐up visits included measurement of exhaled carbon monoxide at the quit date, 2, 6, 10 and 26 weeks. Subjects documented daily cigarette consumption and severity of withdrawal symptoms (Wisconsin scale) from ? 2 weeks to week 2. Outcome measures were withdrawal symptoms composite score and abstinence rates. Findings There was no significant difference in withdrawal symptoms, but more subjects in the AP group were smoke‐free during the 6‐month study period. Overall sustained abstinence was documented in 17% of subjects at 6 months; 22% and 12% for AP and PP, respectively (P = 0.03). Retrospective subgroup analysis showed for subjects smoking >16 cigarettes/day sustained cessation rates were 22% and 9% for AP and PP, respectively (P = 0.01). No difference in adverse event rates was observed. Conclusions Nicotine patch pre‐treatment before cessation did not reduce early withdrawal symptoms but increased sustained abstinence rates at 6 months. The nicotine pre‐treatment was equally effective in light and heavy smokers.     

Marijuana withdrawal and craving: influence of the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes

Aim To examine whether withdrawal after abstinence and cue‐elicited craving were associated with polymorphisms within two genes involved in regulating the endocannabinoid system, cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH). Two single nucleotide polymorphisms (SNPs) in the CNR1 (rs2023239) and FAAH (rs324420) genes, associated previously with substance abuse and functional changes in cannabinoid regulation, were examined in a sample of daily marijuana smokers. Participants Participants were 105 students at the University of Colorado, Boulder between the ages of 18 and 25 years who reported smoking marijuana daily. Measurements Participants were assessed once at baseline and again after 5 days of abstinence, during which they were exposed to a cue‐elicited craving paradigm. Outcome measures were withdrawal and craving collected using self‐reported questionnaires. In addition, urine samples were collected at baseline and on day 5 for the purposes of 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THC–COOH) metabolite analysis. Findings Between the two sessions, THC–COOH metabolite levels decreased significantly, while measures of withdrawal and craving increased significantly. The CNR1 SNP displayed a significant abstinence × genotype interaction on withdrawal, as well as a main effect on overall levels of craving, while the FAAH SNP displayed a significant abstinence × genotype interaction on craving. Conclusions These genetic findings may have both etiological and treatment implications. However, longitudinal studies will be needed to clarify whether these genetic variations influence the trajectory of marijuana use/dependence. The identification of underlying genetic differences in phenotypes such as craving and withdrawal may aid genetically targeted approaches to the treatment of cannabis dependence.     

Is Hepatitis C Infection Associated with Increased Risk of Depression in Persons with Methamphetamine Dependence?

The abuse of methamphetamine (MA) has increased in the United States over the past 15 years and is associated with considerable negative social, psychological, and health effects, including symptoms of depression. Infection with the hepatitis C virus (HCV), which is independently associated with increased risk of depression, is common among MA users, possibly due to high rates of transmission risk behaviors in this cohort (eg, injection drug use). Given the prevalence of depression among HCV-infected individuals and MA users separately, the current study aimed to determine whether HCV infection and MA dependence are associated with additive effects on depression. Focused psychiatric evaluations were conducted on 39 individuals with both MA dependence and HCV infection (MA + HCV +), 57 persons with only MA dependence (MA + HCV -), and a comparison sample of 46 participants with neither risk factor (MA - HCV -). Consistent with prior research, greater self-reported symptoms of depression were observed in the MA + groups relative to MA - HCV - participants; however, there was no evidence to suggest an additive effect of HCV infection. Surprisingly, the prevalence of current and lifetime diagnoses of Major Depressive Disorder (MDD) did not differ across the study groups. Results from this study suggest that HCV infection does not confer an additive effect on the severity of depressive symptoms or the prevalence of major depression in persons with MA dependence.     

Increased self-reported impulsivity in methamphetamine users maintaining drug abstinence

Background: Impulsivity has been proposed as an important factor in the initiation and maintenance of addiction. Indirect evidence suggests that some methamphetamine users report less impulsivity when they are using methamphetamine compared to when abstaining from drug use, but this hypothesis has not been directly tested. Objectives/Methods: In this study, self-reports of impulsivity were obtained from 32 methamphetamine-dependent (DSM-IV) research participants and 41 healthy control subjects, using the Barratt Impulsiveness Scale-11. The methamphetamine users were assessed during an active period of methamphetamine use, as determined through urinalysis, and again after approximately 1 week of confirmed abstinence. Control subjects likewise completed two assessments. A subset of participants also completed serial assessments of the Beck Depression Inventory (Methamphetamine Group, N = 17, Control Group, N = 38) and the Methamphetamine Withdrawal Questionnaire (Methamphetamine Group, N = 12). Results: There was a significant interaction of group with time on impulsivity (p = 0.044), reflecting a significant increase from the first to the second assessment in the methamphetamine users (p = 0.013), but no change among healthy control subjects. In contrast, depressive and withdrawal symptoms significantly decreased between the first and second assessments in the methamphetamine users (ps ≤0.01). Change in impulsivity in methamphetamine users was not significantly correlated with change in withdrawal or depression (ps >0.05). Conclusions: These findings suggest that methamphetamine users report more impulsivity when abstaining from drug use, an effect that is not significantly related to methamphetamine withdrawal. Attenuation of impulsivity may reinforce continued methamphetamine use in these individuals.     

Withdrawal symptoms do not predict relapse among subjects treated for cannabis dependence

This is the first follow-up study on the association between cannabis withdrawal symptoms and risk of relapse to cannabis use. Withdrawal symptoms were assessed in 36 subjects seeking treatment for cannabis dependence. All were free of other substance use or alcohol abuse in the month before abstinence from cannabis. Follow-up was performed 26+/-4 months later, and at this point, the withdrawal symptoms were re-assessed. The following symptoms were significantly elevated after abstinence compared with follow-up: irritability, anger, depression, restlessness, craving, sleep problems, strange dreams, increased appetite, violent outbursts, sweating, hot flashes, chills, and shakiness. This offers further validation of a cannabis withdrawal syndrome. Average withdrawal scores at baseline did not differ with gender, age, treatment type, extent of cannabis use, or a lifetime history of anxiety or affective disorders. Withdrawal scores at baseline did not predict relapse during follow-up.     

Methamphetamine Users in the Psychiatric Emergency Services: A Case-Control Study

The purpose of this study is to examine the sociodemographic, clinical, and service use characteristics of patients with positive methamphetamine (MA) urine toxicology and compare with non-MA users seen in an urban Psychiatric Emergency Services (PES). One hundred twenty patient charts were extracted for demographics, mode of arrival, clinical information, medication treatment of MA-intoxication, and disposition. Compared with non-MA patients, MA patients were significantly younger, male, referred by police, with cardiac symptoms, psychosis, dysphoria, past substance use, and were less likely to have a diagnosis of Schizophrenia, a past psychiatric history/hospitalization, and a history of suicide attempts. Subsequent hospitalization rates did not differ. MA patients treated with medications more readily accepted the referral to chemical dependency treatment. This study shows that hypertension and tachycardia upon arrival to the PES, symptoms of dysphoria and psychosis, past substance use and not having the diagnosis of Schizophrenia are all related to methamphetamine use.     

Methamphetamine users in the psychiatric emergency services: a case-control study

The purpose of this study is to examine the sociodemographic, clinical, and service use characteristics of patients with positive methamphetamine (MA) urine toxicology and compare with non-MA users seen in an urban Psychiatric Emergency Services (PES). One hundred twenty patient charts were extracted for demographics, mode of arrival, clinical information, medication treatment of MA-intoxication, and disposition. Compared with non-MA patients, MA patients were significantly younger, male, referred by police, with cardiac symptoms, psychosis, dysphoria, past substance use, and were less likely to have a diagnosis of Schizophrenia, a past psychiatric history/hospitalization, and a history of suicide attempts. Subsequent hospitalization rates did not differ. MA patients treated with medications more readily accepted the referral to chemical dependency treatment. This study shows that hypertension and tachycardia upon arrival to the PES, symptoms of dysphoria and psychosis, past substance use and not having the diagnosis of Schizophrenia are all related to methamphetamine use.     

Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving

Aims. To compare a transdermal nicotine patch designed for 24-hour wear with one designed for 16-hour wear for relief of craving and withdrawal, particularly in the morning hours. Design. Smokers were randomly assigned to use one of two common patch regimens: NicoDerm/NiQuitin (24-hour wear, 21 mg nicotine) or Nicotrol/Nicorette (16-hour wear, 15 mg). In a double-dummy design, participants wore two patches during the day, one active, one placebo and one patch while sleeping. Setting. A smoking cessation research clinic. Participants. Two hundred and forty-four smokers who suffered morning cravings. Intervention. Two patch formulations approved and marketed for over-the-counter use in the US- NicoDerm CQ (labeled as 21 mg over 24 hours) and Nicotrol (labeled as 15 mg over 16 hours)-were each used according to its instructions. Smokers also received behavioral counseling. Measurements. For a week of baseline and 2 weeks after quitting, smokers used palm-top computers to assess craving and withdrawal symptoms several times each day. Findings. The 21 mg/24-hour patch yielded consistently better control of craving, not only during the morning hours, but throughout the day, and over the 2-week period of abstinence. Additionally, the 21 mg/24-hour patch yielded greater reductions in anxiety, irritability and restlessness. Smokers using the 21 mg/24-hour dosing regimen also experienced longer abstinence than those using the 15 mg/16-hour patch. Conclusions. These findings demonstrate that 24-hour dosing with a 21 mg patch affords superior relief of craving and withdrawal during the first 2 weeks of abstinence, when symptoms are at their peak, and when relapse is most likely. They confirm the importance of dosing parameters in nicotine replacement products.     

Effects of Sensory and Behavioral Substitutes Following an Experimentally Induced Stressor among Abstinent Smokeless Tobacco Users

Despite the well‐known health risks associated with smokeless tobacco use, much is unresolved with respect to effective treatment for use of this substance. The present study examined the impact of a nicotine‐free smokeless tobacco substitute and confectionary chewing gum on craving, withdrawal, and anxiety among 24 smokeless tobacco users following 24 hours of nicotine abstinence and a laboratory stressor. Although chewing gum did not impact withdrawal, craving, or anxiety compared to a no‐product control condition, smokeless tobacco substitute administration resulted in a reduction of withdrawal and craving levels compared to the control condition following 24 hours of abstinence. Furthermore, significantly lower levels of craving and withdrawal were observed in both smokeless tobacco and smokeless tobacco substitute conditions compared to the control condition following the stressor. Results indicate that although general oral stimulation (eg, chewing gum) was not effective in reducing symptoms related to nicotine withdrawal, smokeless tobacco substitute use appears to be helpful in reducing withdrawal levels post‐stressor. These data suggest that use of a smokeless tobacco substitute may be an effective aid in helping individuals wishing to quit, especially when managing stressors. (Am J Addict 2010;00:1–8)     

The prevalence of psychotic symptoms among methamphetamine users

AIMS: To examine the prevalence of psychotic symptoms among regular methamphetamine users. DESIGN: Cross-sectional survey. SETTING: Participants were recruited from Sydney, Australia, through advertisements in free-press magazines, flyers and through word-of-mouth. PARTICIPANTS: Methamphetamine users (n = 309) who were aged 16 years or over and took the drug at least monthly during the past year. MEASUREMENTS: A structured face-to-face interview was used to assess drug use, demographics and symptoms of psychosis in the past year. Measures of psychosis included: (a) a psychosis screening instrument derived from the Composite International Diagnostic Interview; and (b) the Brief Psychiatric Rating Scale subscales of suspiciousness, unusual thought content, and hallucinations. Dependence on methamphetamine was measured using the Severity of Dependence Scale. FINDINGS: Thirteen per cent of participants screened positive for psychosis, and 23% had experienced a clinically significant symptom of suspiciousness, unusual thought content or hallucinations in the past year. Dependent methamphetamine users were three times more likely to have experienced psychotic symptoms than their non-dependent counterparts, even after adjusting for history of schizophrenia and other psychotic disorders. CONCLUSION: The prevalence of psychosis among the current sample of methamphetamine users was 11 times higher than among the general population in Australia. Dependent methamphetamine users are a particularly high-risk group for psychosis.     

A randomized controlled trial of oral selegiline plus nicotine skin patch compared with placebo plus nicotine skin patch for smoking cessation

Objectives To compare the effect of oral selegiline plus nicotine patch with placebo plus nicotine patch on smoking cessation rates. Design Randomized double‐blind placebo‐controlled trial. Setting Three community‐based clinics. Participants One hundred and nine male and female smokers aged 18–55 years, who smoked at least 15 cigarettes/day. Interventions Oral selegiline, 2.5 mg, or placebo twice/day initiated 1 week before the quit day, followed by 5 mg oral selegiline or placebo twice daily for 26 weeks, plus active nicotine skin patch to all participants for the first 8 weeks only. Measures of continuous abstinence rates up to 52 weeks, withdrawal symptoms, blood pressure and adverse events incidence. Findings Twenty‐five per cent (14 of 56) were continuously abstinent for 52 weeks in the selegiline plus nicotine group compared with 11% (6 of 53) in the placebo plus nicotine group (P = 0.08). Craving for cigarettes was lower in the selegiline plus nicotine group 4 weeks after quit day (P = 0.02). Conclusions Adding selegiline to nicotine patch was associated with a doubling of the 52‐week continuous abstinence rate, but this difference was not statistically significant. Selegiline significantly reduced craving for cigarettes and appeared to mitigate the need for nicotine replacement therapy. The results suggest that selegiline is a promising drug for future smoking cessation research.     

Double-blind placebo-controlled evaluation of the PROMETA™ protocol for methamphetamine dependence

Aims To evaluate the efficacy and safety of the PROMETA? Protocol for treating methamphetamine dependence. Design A double‐blind, placebo‐controlled 108‐day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with active hydroxazine only). Setting Three substance abuse treatment clinics: two in‐patient, one out‐patient. Participants Treatment‐seeking, methamphetamine‐dependent adults (n = 120). Measurements Primary outcome was percentage of urine samples testing negative for methamphetamine during the trial. Findings No statistically significant between‐group differences were detected in urine drug test results, craving, treatment retention or adverse events. Conclusions The PROMETA protocol, consisting of flumazenil, gabapentin and hydroxyzine, appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving.     

Can Cocaine Craving Be a Medication Development Outcome?

Craving, which ranges from a sustained desire for drugs persisting for weeks to an acute desire passing within minutes, has been described as an important clinical precipitant of relapse in cocaine and opioid abusers and may be a useful surrogate outcome for developing new drug abuse pharmacotherapies. Whereas craving for opioids frequently has been conceptualized as the negative reinforcer of protracted withdrawal or “drug hunger,” craving for cocaine has been conceptualized as the positive reinforcer of remembered euphoria. Medications can reduce both sustained cocaine craving and acute craving induced by a single dose of cocaine, and reductions in both types of craving are correlated with reductions in cocaine use. Furthermore, high levels of craving during treatment or during cue-induced challenges predict poor treatment response and later relapse to cocaine abuse in those who have attained abstinence.