Prospective memory impairment in former users of methamphetamine

Rationale  Considerable research indicates that methamphetamine use is associated with neurocognitive impairment, but no empirical study to date has assessed whether these difficulties extend to memory for future intentions (prospective memory). Objectives  The present study assessed prospective performance on a laboratory measure of prospective memory that closely represents the types of prospective memory tasks that actually occur in everyday life and provides an opportunity to investigate the different sorts of prospective memory failures that occur (“Virtual Week”). Materials and methods  Twenty adults with confirmed history of methamphetamine use and dependence, currently engaged in rehabilitation and confirmed to be abstinent for an average period of 6 months, and 20 methamphetamine-naive participants were tested on Virtual Week. Various other aspects of cognitive function were also assessed, including retrospective memory and executive functioning. Results  Methamphetamine users were significantly impaired on Virtual Week, and these deficits did not vary as a function of specific prospective memory task demands. Of all the cognitive measures, cognitive inhibition shared greatest variance with group effects on the prospective memory measure. Conclusions  Prospective memory performance is sensitive to prior methamphetamine use even well into abstinence. Methamphetamine users experience generalized difficulties with prospective memory, suggesting that these deficits are likely to have important implications for day-to-day functioning.     

Emergency management of inadvertent accelerated opiate withdrawal in dependent opiate users

Six opiate-dependent drug users presented to the local emergency department within a 10-day period with symptoms of severe opioid withdrawal immediately following intravenous use of recently acquired street 'heroin'. The withdrawal picture was similar to that described in patients undergoing rapid opioid detoxification, suggesting that the substance injected was contaminated with an opiate antagonist. A number of potential compounds are discussed, including naltrexone and buprenorphine, and recommendations for the medical management of severe opiate withdrawal within an emergency setting are outlined. [Lubman DI, Koutsogiannis Z, Kronborg I. Emergency management of inadvertent accelerated opiate withdrawal in dependent opiate users. Drug Alcohol Rev 2003;2:433 - 436]     

Comparatively preserved impulse control in late-onset opiate users

Rationale

A substantial literature indicates that in alcohol addiction aspects of impulsive decision-making are typical of individuals with an early onset of addictive behaviour problems. It is not known whether the same applies to opiate addiction, and this insight has important theoretical and clinical implications.

Objectives

This study aims to examine the relationship between age at onset of addictive behaviour problems and decision-making in opiate addiction.

Methods

Ninety-three opiate-dependent, treatment-seeking individuals were divided in three groups, early, late and intermediate onset of problems, and completed impulsivity questionnaires and delay discounting and gambling tasks.

Results

Individuals with a late onset of opiate problems (25 years or above) had lower delay discounting rates than individuals with early (18 years or less) or intermediate onset. There were no differences in performance on the gambling tasks. Late-onset individuals were older and had shorter drug histories, but there was no relationship between either age or length of exposure to opiates and delay discounting rates.

Conclusions

In keeping with previous studies in alcohol addiction, these findings support the notion of at least two distinct subgroups of opiate-dependent individuals, characterised by a different onset of problems, different propensity to impulsive behaviour and perhaps distinct mechanisms leading to addiction.     

Prospective memory,everyday cognitive failure and central executive function in recreational users of Ecstasy

Chronic use of MDMA (3,4-methylenedioxymethamphetamine), or Ecstasy, is believed to lead to impaired psychological performance, including well-documented decrements in laboratory and field tests of retrospective memory. Less is known about the impact of Ecstasy on aspects of 'everyday' memory, despite obvious concerns about such effects. The three studies reported here focused on the impact of chronic Ecstasy use on prospective memory (PM), associated central executive function and other aspects of day-to-day cognition. In study 1 46 regular Ecstasy users were compared with 46 Ecstasy-free controls using the Prospective Memory Questionnaire (PMQ). Ecstasy users reported significantly more errors in PM (remembering to do something in the future); these findings persisted after controlling for other drug use and the number of strategies used to aid memory. No difference was found between representative subgroups on the Lies Scale of the Eysenck Personality Questionnaire. In study 2 a different group of 30 regular Ecstasy users and 37 Ecstasy-free controls was assessed on the PMQ and on a central executive task comprising verbal fluency measures. The results confirmed the significant impairments in long- and short-term PM and revealed corresponding impairments in verbal fluency. In study 3 15 Ecstasy users, 15 cannabis users and 15 non-drug users were assessed using the Cognitive Failures Questionnaire, which requires participants to provide ratings of the frequency of various day-to-day cognitive slips. The results indicate that the Ecstasy users did not perceive their general cognitive performance to be worse than that of controls. Taken together, these results suggest that Ecstasy users have impaired PM that cannot be explained by an increased propensity to exaggerate cognitive failures. These may be attributable, in part, to central executive deficits that are due to frontal lobe damage associated with Ecstasy use. Copyright 2001 John Wiley & Sons, Ltd.     

Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

Rationale  

Prospective memory (PM) deficits in recreational drug users have been documented in recent years. However, the assessment of PM has largely been restricted to self-reported measures that fail to capture the distinction between event-based and time-based PM. The aim of the present study is to address this limitation.     

Mortality of opiate users in Vienna, Austria.

The purpose of this study was to investigate whether there are differences in overall and cause-specific mortality rates of opiate users in maintenance treatment and of opiate users not in any drug treatment program in Vienna, Austria. A cohort of opiate-users enrolled in maintenance treatment in Vienna and a cohort of individuals involved in opiate-related emergencies from 1995 to 1997 were retrospectively analyzed. The standardized mortality rate of opiate-users enrolled in maintenance treatment was 12.1 and that of individuals involved in opiate-related emergencies was 48.8. Excess mortality was found for all categories for both groups. In the face of the extremely high excess mortality of opiate users involved in opiate-related emergencies, measures have to be taken to get these individuals in drug treatment programs as soon as possible.     

Long-term effects of ketamine: evidence for a persisting impairment of source memory in recreational users

RATIONALE: Ketamine is an N-methyl-d-aspartate (NMDA)-receptor antagonist that is increasingly being used as a recreational drug. Previous research has shown gross generalised verbal memory impairments persisting 3 days after ketamine use in chronic users, however episodic memory has not specifically investigated in this population. OBJECTIVE: To determine whether ketamine, on the night of drug use (day 0) and 3 days later, is associated with impaired episodic memory as assessed by a source memory task. METHODS: Twenty ketamine users and 20 poly-drug controls were compared on a source memory task both on day 0 and 3. Participants also completed questionnaires on both days indexing schizophrenic-like and dissociative symptoms. RESULTS: On day 0, ketamine abusers were impaired on both source memory and item recognition and scored more highly on schizophrenic and dissociative symptom scales compared to poly-drug controls. On day 3 ketamine abusers only displayed source memory impairments and these positively correlated with the level of schizophrenic-like symptoms on day 0. No differences on day 3 in schizophrenic-like or dissociative symptoms were observed. CONCLUSIONS: Ketamine abusers exhibit a persisting deficit in source memory on day 3 but not in item recognition. These findings suggest that repeated use of ketamine produces chronic impairments to episodic memory.     

Deficits of long-term memory in ecstasy users are related to cognitive complexity of the task

Rationale  

Despite animal evidence that methylenedioxymethamphetamine (ecstasy) causes lasting damage in brain regions related to long-term memory, results regarding human memory performance have been variable. This variability may reflect the cognitive complexity of the memory tasks. However, previous studies have tested only a limited range of cognitive complexity. Furthermore, comparisons across different studies are made difficult by regional variations in ecstasy composition and patterns of use.     

The pharmacokinetics of methadone in healthy subjects and opiate users

Aims There is some evidence that monitoring methadone plasma concentration may be of benefit in dosage adjustment during methadone maintenance therapy for heroin (opiate) dependence. However, the kinetics of oral methadone are incompletely characterized. We attempted to describe the latter using a population approach combining intensive 57 h sampling data from healthy subjects with less intensive sparse 24 h data from opiate users. Methods Single oral doses of rac-methadone were given to 13 drug-naive healthy subjects (7 men and 6 women) and 17 opiate users beginning methadone maintenance therapy (13 men and 4 women). Plasma methadone concentrations were measured by h.p.l.c. Kinetic analysis was performed using the P-Pharm software. Results Comparison of kinetic models incorporating mono- or biexponential disposition functions indicated that the latter best represented the data. The improvement was statistically significant for the data from healthy subjects whether the full 57 h or truncated 24 h profiles were used (P<0.031 and P<0.024, respectively), while it was of borderline significance for the more variable data from opiate users (P=0.057) or for pooled (healthy subjects and opiate users) data (P=0.066). The population mean oral clearance of methadone was 6.9±1.5 s.d. l h⁻¹ (5.3±1.2 s.d. l h⁻¹ using 0–24 h data) in the healthy subjects. The results of separate analyses of the data from opiate users and healthy subjects were in contrast with those obtained from pooled data analysis. The former indicated a significantly lower clearance for opiate users (3.2±0.3 s.d. l h⁻¹, P<0.001); 95% CI for the difference=−3 to −6 l h⁻¹ and no difference in the population mean values of V /F (212±27 s.d. l and 239±121 s.d. l, P=0.15), while according to the latter analysis addiction was a covariate for V /F but not for oral clearance. A slower absorption of methadone in opiate users was indicated from the analysis of both pooled and separate data. The median elimination half-life of methadone in healthy subjects was 33–46 h depending on the method used to calculate this parameter. Conclusions Estimates of the long terminal elimination half-life of methadone (33–46 h in healthy subjects and, possibly, longer in opiate users) indicated that accurate measurement of this parameter requires a duration of sampling longer than that used in this study. Our analysis also suggested that parameters describing plasma concentrations of methadone after a single oral dose in healthy subjects may not be used for predicting and adjusting dosage in opiate users receiving methadone maintenance therapy unless coupled with feedback concentration monitoring techniques (for example Bayesian forecasting).     

Everyday memory deficits in ecstasy-polydrug users

Recent research suggests that not only does the use of recreational drugs impact on working memory functioning, but more ;everyday' aspects of memory (e.g. remembering to do something in the future) are also affected. Forty-three ecstasy-polydrug users and 51 non-ecstasy users were recruited from a university population. Each participant completed the Cognitive Failures Questionnaire (CFQ) and Everyday Memory Questionnaire (EMQ). Of these, 28 ecstasy-polydrug users and 35 non-ecstasy users completed the Prospective Memory Questionnaire (PMQ). In addition, an objective measure of cognitive failures (the CFQ-for-others) was completed by friends of participants. With the exception of the CFQ-for-others, in each regression equation, cannabis emerged as the only significant predictor of everyday and prospective memory deficits. Significant correlations were found between the different indicators of everyday memory and various measures of illicit drug use. Cannabis featured prominently in this respect. The present study provides further support for cannabis related deficits in aspects of everyday memory functioning. Ecstasy may aLso be associated with cognitive slips, but not to the same extent as cannabis.     

Illicit tranquilliser use and dependence among female opiate users

This study determined the predictors of 12-month dependence on illicit tranquillisers among female opiate users attending three services in Glasgow, Scotland, UK. Twelve-month drug dependence was measured using the Diagnostic Interview Schedule. The Revised Clinical Interview Schedule (CIS-R) measured current neurotic symptoms. 60% (159/266) had used illicit tranquillisers in the past 30 days, and 50% (132/266) met criteria for 12-month dependence on illicit tranquillisers. Polydrug use, injecting drug use, childhood and adulthood abuse, adverse life experiences and current and previous mental health problems were associated with 12-month dependence on illicit tranquillisers. Using multiple logistic regression, polydrug use in last 30 days (OR 3.2, 95% CI 1.5 - 7.0), history of deliberate self-harm (OR 2.5, 95% CI 1.4 - 4.4), history of injecting drug use (OR 2.5, 1.2 - 5.2) and likely to need treatment for current neurotic symptoms (CIS-R ≥ 18) (OR 2.4, 95% CI 1.3 - 4.4) predicted 12-month dependence on illicit tranquillisers. Drug users in general and female drug users in particular who are using illicit tranquillisers are also particularly likely to have psychiatric symptoms requiring treatment. Mental health problems should be assessed and monitored among this client group and counselling and psychosocial support should be provided when indicated. [Gilchrist G, Atkinson J, Gruer L. Illicit tranquilliser use and dependence among female opiate users. Drug Alcohol Rev 2006;25:459 - 461]     

Punishment induces risky decision-making in methadone-maintained opiate users but not in heroin users or healthy volunteers.

Reinforcing properties of psychoactive substances are considered to be critically involved in the development and maintenance of substance dependence. While accumulating evidence suggests that the sensitivity to reinforcement values may generally be altered in chronic substance users, relatively little is known about the influence reinforcing feedback exerts on ongoing decision-making in these individuals. Decision-making was investigated using the Cambridge Risk Task, in which there is a conflict between an unlikely large reward option and a likely small reward option. Responses on a given trial were analyzed with respect to the outcome on the previous trial, providing a measure of the impact of prior feedback in modulating behavior. Five different groups were compared: (i) chronic amphetamine users, (ii) chronic opiate users in methadone maintenance treatment (MMT), (iii) chronic users of illicit heroin, (iv) ex-drug users who had been long-term amphetamine / opiate users but were abstinent from all drugs of abuse for at least 1 year and (v) matched controls without a history of illicit substance use. Contrary to our predictions, choice preference was modified in response to feedback only in opiate users enrolled in MMT. Following a loss, the MMT opiate group chose the likely small reward option significantly less frequently than controls and heroin users. Our results suggest that different opiates are associated with distinctive behavioral responses to feedback. These findings are discussed with respect to the different mechanisms of action of heroin and methadone.Neuropsychopharmacology (2005) 30, 2115-2124. doi:10.1038/sj.npp.1300812; published online 6 July 2005.     

Differences in orbitofrontal activation during decision-making between methadone-maintained opiate users, heroin users and healthy volunteers

Objective Previously, we reported that opiate users enrolled in methadone treatment made ‘risky’ choices on a decision-making task following a loss of points compared with heroin users and healthy volunteers. One possible explanation for this behaviour is that methadone users were less sensitive to punishment on immediately preceding unsuccessful trials.Methods We sought to explore this finding from a neural perspective by performing a post hoc analysis of data from a previous positron emission tomography study. We restricted the analysis to the opiate groups and controls, assessing differences between opiate users on methadone and those on heroin.Results We found significant over-activation in the lateral orbitofrontal cortex (OFC) in methadone users compared with both heroin users and controls concomitant with the greatest overall tendency to ‘play risky’. Heroin users showed significant under-activation in this area compared with the other two groups whilst exhibiting the greatest overall tendency to ‘play safe’. Correlational analysis revealed that abnormal task-related activation of the left OFC was associated with the dose of methadone in methadone users and with the duration of intravenous heroin use in heroin users. ‘Playing safe’ following a loss of points was also negatively correlated with the activation of pregenual anterior cingulate and insula cortex in controls, but not in opiate users.Conclusion Our findings suggest that the interplay between processes involved in integrating penalty information for the purpose of response selection may be altered in opiate users. This change was reflected differentially in task-related pattern of OFC activation depending on the opiate used.     

Predictors of heroin abstinence in opiate substitution therapy in heroin-only users and dual users of heroin and crack

AimsTo analyse predictors of heroin abstinence in opiate substitution therapy (OST) based on frequency of crack use and its interactions with other predictors in a clinical non-experimental setting.DesignRetrospective study.SettingA community drug service in London, UK.Participants325 clients starting OST between 2010 and 2014 (197 methadone and 128 buprenorphine).MeasurementsLogistic regression models (a general model and separate models for methadone and buprenorphine) assessed demographic and clinical data as predictors of heroin abstinence at one year after treatment start (or at the date of transfer to another service).FindingsFor the general model participants choosing methadone were more likely to use heroin at follow up (OR = 2.36, 95% CI: 1.40–3.17) as were daily crack users on methadone (OR = 2.62, 95% CI: 0.96–7.16).For the methadone model only daily crack use predicted heroin use at follow up (OR = 2.62, 95% CI: 0.96–7.16).For buprenorphine, higher amounts of baseline heroin use, lower buprenorphine dose and daily drinking predicted heroin use at follow up (OR = 0.85, 95% CI: 0.75–0.95; OR = 1.31, 95% CI: 1.06–1.60 and OR = 6.04, 95% CI: 1.26–28.92). Both use of cannabis and depression increased likelihood of heroin abstinence for clients not using crack compared to occasional (OR = 6.68, 95% CI: 0.37–119.59; OR = 106.31, 95% CI: 3.41–3313.30) and daily (OR = 57.49 (95% CI: 2.37–1396.46; OR = 170.99 (95% CI: 4.61–6339.47) users.ConclusionsMost of the predictors in the general model were found significant only in the buprenorphine but not in the methadone model, suggesting that a general model has little predictive value. Crack use was a significant predictor of heroin abstinence at follow up in all models, however for buprenorphine only when depression or cannabis use was present. Further research is needed to assess effective treatment approaches for the growing population of dual users.     

Chronic morphine affects working memory during treatment and withdrawal in rats: possible residual long-term impairment

An eight-arm radial maze was used to investigate a possible short-term (during the development of tolerance and dependence) and long-term (6, 9 and 12 months after treatment) effect on working memory, in young rats, which drank morphine (0.5mg/ml) for 1 month, or to which the drug was administered by i.p. injection (at weekly increasing doses of 20, 50, 100, 200mg/kg). Tail flick test and cortically derived electroencephalographic (EEG) recordings were also carried out in the same rats to determine any modifications in analgesia and in total EEG mean power spectra during treatment and withdrawal. Complete tolerance to morphine analgesia developed during the period of drug treatment. Chronic morphine significantly impaired radial maze performance in the working memory components of the task during both treatment and early withdrawal, but only in the i.p. group. Six and 9 months after morphine treatment, both the oral and i.p. group showed a significant impairment of radial maze performance. The mean power spectra were altered during treatment but returned to baseline values during abstinence, except for the first day. These findings suggest the possibility of morphine-induced premature ageing, which is more evident in i.p. treated animals. The mechanism by which morphine treatment produces residual long-term learning impairment requires further elucidation.     

Attention and memory in illicit amphetamine users

The purpose of this study was to assess cognitive functioning in a group of illicit amphetamine users. A neuropsychological test battery (Wechsler Memory Scale-Revised (WMS-R) and the digit symbol, block design and vocabulary subtests of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the National Adult Reading Test (NART)) was administered to 78 amphetamine users (mean age=22.5 years; 46 males, 33 females). Severity of amphetamine dependence was found to be associated with poorer performance on both memory and attention/concentration indices of the WMS-R. The relative contribution of amphetamine dependence, concurrent drug use and other drug related factors to neuropsychological functioning are discussed.     

Population pharmacokinetics of methadone in opiate users: characterization of time-dependent changes

AIMS: Although methadone is widely used to treat opiate dependence, guidelines for its dosage are poorly defined. There is increasing evidence to suggest that a strategy based on plasma drug monitoring may be useful to detect non-compliance. Therefore, we have developed a population-based pharmacokinetic (POP-PK) model that characterises adaptive changes in methadone kinetics. METHODS: Sparse plasma rac-methadone concentrations measured in 35 opiate-users were assessed using the P-Pharm software. The final structural model comprised a biexponential function with first-order input and allowance for time-dependent change in both clearance (CL) and initial volume of distribution (V ). Values of these parameters were allowed to increase or decrease exponentially to an asymptotic value. RESULTS: Increase in individual values of CL and increase or decrease in individual values of V with time was observed in applying the model to the experimental data. CONCLUSIONS: A time-dependent increase in the clearance of methadone is consistent with auto-induction of CYP3A4, the enzyme responsible for much of the metabolism of the drug. The changes in V with time might reflect both up- and down-regulation of alpha1-acid glycoprotein, the major plasma binding site for methadone. By accounting for adaptive kinetic changes, the POP-PK model provides an improved basis for forecasting plasma methadone concentrations to predict and adjust dosage of the drug and to monitor compliance in opiate-users on maintenance treatment.