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Cocaine Use and Withdrawal: The Effect on Sleep and Mood
Abstract
Three recreational cocaine users (age, 26.7 years), after one adaptation night, spent 5 days and nights in the laboratory where their EEG, EOG, and submental EMG were recorded during all of their sleep. On the second afternoon and evening of the study, subjects used an estimated 1 to 2 g cocaine intranasally. They all slept between 2:00 A.M. and 9:00 A.M. that night. Blood samples were drawn each evening and morning. Absolute plasma cocaine levels and patterns of elimination were consistent with subjects report of dose and time of administration. Mood ratings were made repeatedly throughout the study. There was suppression of REM sleep during the use of cocaine followed by a rebound which is specific to REM sleep and is not seen in other stages of sleep. REM variables subsided to normal levels on the third recovery night following cocaine use.
... Acute cocaine administration can increase sleep latency [104,162,207], but the first few days of abstinence from cocaine in chronic users is associated with short sleep latencies relative to later in abstinence [81,121,138,148,153,192], when sleep latency may be as long as 30-60 min or more ( Table 2). ...
... Cocaine administration acutely suppresses REM sleep [104,162,207], with a subsequent rebound evident as an increase in REM sleep time and/or percent of total sleep time spent in REM (REM%), and a decrease in REM latency [81,104,121,149,153,192,207]. However, in chronic cocaine users, REM sleep decreases following the rebound, with low REM times observed during the second and third weeks of abstinence [13,104,138,147,149,153,192] (Table 2). ...
... Cocaine administration acutely suppresses REM sleep [104,162,207], with a subsequent rebound evident as an increase in REM sleep time and/or percent of total sleep time spent in REM (REM%), and a decrease in REM latency [81,104,121,149,153,192,207]. However, in chronic cocaine users, REM sleep decreases following the rebound, with low REM times observed during the second and third weeks of abstinence [13,104,138,147,149,153,192] (Table 2). ...
Sleep abnormalities are associated with acute and chronic use of addictive substances. Although sleep complaints associated with use and abstinence from addictive substances are widely recognized, familiarity with the underlying sleep abnormalities is often lacking, despite evidence that these sleep abnormalities may be recalcitrant and impede good outcomes. Substantial research has now characterized the abnormalities associated with acute and chronic use of alcohol, cannabis, cocaine, and opiates. This review summarizes this research and discusses the clinical implications of sleep abnormalities in the treatment of substance use disorders.
... Both recent cocaine administration (<24h since use) and acute cocaine withdrawal (>24h since use) have been reported to adversely affect objective measures of sleep quality. For example, both recent cocaine administration and withdrawal prolong sleep onset latency (SOL), reduce total sleep time (TST) and decrease sleep efficiency (SE) (Post et al., 1974;Watson et al., 1992;Johanson et al., 1999;Schierenbeck et al., 2008). Cocaine administration decreases REM sleep (Post et al., 1974;Watson et al., 1992;Johanson et al., 1999;Schierenbeck et al., 2008), while cocaine withdrawal increases REM sleep percentage and decreases REM latency (Post et al., 1974;Kowatch et al., 1992;Watson et al., 1992;Gillin et al., 1994;Johanson et al., 1999;Schierenbeck et al., 2008); however, since sleep time in cocaine-dependent individuals is dramatically reduced when compared to healthy controls, there is not an overall increase in REM sleep. ...
... For example, both recent cocaine administration and withdrawal prolong sleep onset latency (SOL), reduce total sleep time (TST) and decrease sleep efficiency (SE) (Post et al., 1974;Watson et al., 1992;Johanson et al., 1999;Schierenbeck et al., 2008). Cocaine administration decreases REM sleep (Post et al., 1974;Watson et al., 1992;Johanson et al., 1999;Schierenbeck et al., 2008), while cocaine withdrawal increases REM sleep percentage and decreases REM latency (Post et al., 1974;Kowatch et al., 1992;Watson et al., 1992;Gillin et al., 1994;Johanson et al., 1999;Schierenbeck et al., 2008); however, since sleep time in cocaine-dependent individuals is dramatically reduced when compared to healthy controls, there is not an overall increase in REM sleep. ...
... For example, both recent cocaine administration and withdrawal prolong sleep onset latency (SOL), reduce total sleep time (TST) and decrease sleep efficiency (SE) (Post et al., 1974;Watson et al., 1992;Johanson et al., 1999;Schierenbeck et al., 2008). Cocaine administration decreases REM sleep (Post et al., 1974;Watson et al., 1992;Johanson et al., 1999;Schierenbeck et al., 2008), while cocaine withdrawal increases REM sleep percentage and decreases REM latency (Post et al., 1974;Kowatch et al., 1992;Watson et al., 1992;Gillin et al., 1994;Johanson et al., 1999;Schierenbeck et al., 2008); however, since sleep time in cocaine-dependent individuals is dramatically reduced when compared to healthy controls, there is not an overall increase in REM sleep. ...
The goal of this project was to evaluate the relationship between self-reported sleep habits, daytime sleepiness, and drug use variables in individuals with cocaine and methamphetamine (METH) use disorders. Participants with a cocaine or meth use disorder completed questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and a demographic/drug use form. Participants with a cocaine (N=51) or meth use disorder (N=85) were separated into those with either high or low sleep deficits. In participants with a cocaine use disorder, ANOVA revealed significantly higher ESS scores among those defined as "poor sleepers" (with a PSQI score >5) when compared to those defined as "good sleepers" (with a PSQI score ≤5). In addition, poor sleepers reported using cocaine for more days out of the past 30 when compared to good sleepers. Interestingly, good sleepers reported using more grams of cocaine/day compared to poor sleepers. In participants with a METH use disorder, ANOVA revealed significantly higher ESS scores among poor sleepers when compared to good sleepers. Finally, individuals with a METH use disorder that endorsed elevated daytime sleepiness also had significantly higher PSQI scores when compared to those with normal daytime sleepiness. The results indicate that drug use variables, such as recent and daily use, may affect sleep quality and daytime sleepiness in individuals with stimulant use disorders; however, further investigations (i.e. in cocaine and METH users that do not meet criteria for a cocaine or METH use disorder) must be conducted in order to provide more conclusive evidence of the impact these usage variables may have on these sleep characteristics.
... Total sleep time did not change during acute withdrawal, but it did decrease during subacute withdrawal. Others have reported that changes in sleep, namely increased sleep time, increased REM, and decreased REM latency, dissipated within 3 days after cessation of cocaine use (Watson, Bakos, Compton, & Gawin, 1992). Unfortunately, in none of these studies were the levels of cocaine exposure during the last binge (period of use), cumulative history of cocaine exposure, or extent of other drug use of the participants. ...
... Other changes in sleep patterns-decreased sleep efficiency, increased REM latency, and decreased %REM-were also present. Similar effects have been found in other studies, although in most cases cocaine had not been administered under controlled conditions although sleep was monitored polysomnographically (Post, Gillin, Wyatt, & Goodwin, 1974;Watson et al., 1992). There was little evidence of improvement in these parameters across the 5-day period of Phase 2. This lack of improvement may indicate that tolerance does not develop quickly to these effects. ...
... Another limitation of this study was the failure to continue Phase 3 until sleep was normalized or had reached a stable level. Other studies have demonstrated similar types of disturbances continuing at least 3 weeks, although others have shown the emergence of normal sleep patterns after a very short period of abstinence (Kowatch et al., 1992;Thompson et al., 1995;Watson et al., 1992;Weddington et al., 1990). The problem with these other studies, however, was that cocaine use was only documented by self-report, making it difficult to compare to the present study and in the Weddington et al. (1990), sleep was not measured polysomnographically. ...
The effects of cocaine use and withdrawal on mood and sleep were examined. Three cocaine-dependent men lived in an inpatient facility for approximately 4 weeks, which included an initial abstinence phase (8-10 days), a cocaine administration phase (5 days), and a 2nd abstinence phase (14-16 days). During the 2nd phase, cocaine was administered intranasally a few hours before bedtime. During the day, mood and daytime sleepiness were measured, and sleep was monitored each night. Cocaine produced typical changes in mood and blood pressure, and sleep was severely disrupted. Following Phase 2, there were no changes in mood that was indicative of an abstinence syndrome, although, initially, daytime sleepiness increased. After 2 weeks, sleep architecture remained different from age-matched controls. This study is the first to measure changes in sleep architecture polysomnographically following a period of controlled cocaine use.
... The case report by Subramanya and Ramachandran (2006) describes a sleep profile which may have been induced by chronic cocaine consumption (see Table 8). There are additional, confirmatory data upon the sleep during cocaine binges from the studies by Watson et al. (1992), Johanson et al. (1999), Pace-Schott et al. (2005a) and Morgan et al. (2006). These articles will be discussed below in the section "PSG measures during cocaine withdrawal". ...
... Three of these lacked specificity for cocaine (Gillin et al., 1994;Thompson et al., 1995;Lukas et al., 1996). The time course of abstinence until the subacute phase was also addressed in all but two (Watson et al., 1992;Lukas et al., 1996) of these investigations. ...
... In order to study the presumed similarity between cocaine and amphetamines with respect to their neuropharmacologic action, Watson et al. (1992) recruited three healthy recreational intranasal cocaine users. The individuals (ages 24 to 32) reported having used cocaine about 25 times per year for a mean of 3.5 years. ...
This systematic review on illicit recreational drugs and sleep investigated the effects of cocaine, MDMA, MDE, LSD and cannabis upon subjective and objective measures of sleep, both after drug administration and during withdrawal. It also examined whether, on the other hand, sleep disturbances affect an individual’s propensity to use these drugs. The electronic databases Medline, Embase, CINAHL, PsycINFO and Psyndex were searched for all studies on these substances in conjunction with sleep, and reference lists of eligible articles were screened for further relevant studies. Articles published until October 2006 were eligible. 88 out of a total of 1200 studies were identified for analysis and twelve further studies were added when scrutinizing the reference lists. Meta-analyses were performed only for cocaine withdrawal, since number, quality and homogeneity of the other studies did not permit such analyses.
This dissertation has revealed the limitations of the available data. Studies have been flawed by a large number of methodological difficulties, some rather inevitable, some due to less rigorous standards of methodology in the past decades. It has been pointed out where future research is needed the most.
Acute administration of cocaine, MDMA and MDE increases wakefulness and suppresses REM sleep. These substances share a common pattern of acute effects on sleep with other psychostimulants such as amphetamine. LSD may have similar acute effects, but there is conflicting evidence.
In patients withdrawing from cocaine, sleep continuity measures resemble those of primary insomniacs. Even in the absence of depressed mood, REM sleep latency is not much longer than in depressed patients. After the first ten days of abstinence, sleep continuity measures deteriorate even further. Interestingly, the patients do not recognize this deterioration. It is accompanied by a worsening in cognitive performance.
Heavy ecstasy users often complain of persistent sleep disturbances. PSG studies have indicated that in abstaining heavy ecstasy users, stage 2 sleep, TST and SE are reduced. These findings can be interpreted as related to MDMA-induced serotonin neurotoxicity in humans.
Acute administration of THC increases stage 4 sleep and reduces REM sleep. After repeated administration of marijuana, tolerance develops to SWS effects. Upon withdrawal, SOL is elevated, SE is reduced and an REM rebound can be observed. Sleep disturbances constitute one of the most frequently reported symptoms of cannabis withdrawal. There is evidence suggesting that THC can be a treatment alternative for circadian rhythm disturbances, e.g. in patients with dementia and nighttime agitation.
Although some studies have shown that in patients with sleep disturbances the prevalence of drug abuse is elevated and that the incidence of new onset of an illicit drug use disorder is increased, an independent correlation or even a causal relationship has not been established. No studies have been conducted that investigated the predictive value of objective sleep disturbances during cocaine and cannabis withdrawal for treatment outcome. There are limited data on the predictive value of drug dreams during cocaine withdrawal.
... prolonged wakefulness during use and hypersomnia during early withdrawal). It has become increasingly clear, however, that reproducible sleep disturbances associated with cocaine dependence are not limited to periods of acute intoxication or early withdrawal, but are also present in periods of sustained abstinence [8][9][10][11][12]. Furthermore, these sleep disturbances are associated with parallel deficits in cognitive performance [8,13] that might affect treatment retention and promote relapse [14]. ...
... REM sleep is altered in chronic cocaine users, and appears to vary widely depending on recency of cocaine use, with evidence for an initial suppression followed by a rebound [9][10][11][12]. Furthermore, recent work has shown that cocaine has both immediate [23] and abstinence-related [8] effects on slow-wave brain activity. ...
... The decrease in REM latency that led to the increase in first-quarter REM sleep is not unprecedented, but rather a consistent finding in the largely male cohorts of cocaine users examined in the first week of abstinence [9][10][11]. More recent evidence suggests that cocaine use increases slow-wave activity acutely [23] and that total slow-wave activity during sleep decreases in the first week of abstinence relative to post-drug nights [8]. ...
Disturbances in sleep associated with chronic cocaine use may underlie abstinence-related cognitive dysfunction. We hypothesized that sleep-related cognitive function would be impaired in chronic cocaine users, and that this impairment would be associated with abstinence-related changes in sleep architecture.
Twelve chronic cocaine users completed a 23-day in-patient study that included randomized, placebo-controlled, cocaine self-administration sessions. We report polysomnographic measurement of rapid eye-movement (REM) sleep and slow-wave activity, and performance on a visual texture discrimination task.
Progressive abstinence from cocaine was associated with characteristic changes in REM sleep. REM sleep was shortest on nights following cocaine use and rebounded in the first week of abstinence before diminishing with progressive abstinence, following a pattern opposite that of slow-wave activity. Overnight visual learning was observed over the first night following 3 consecutive days of laboratory cocaine use; however, learning was not observed at 3 days or 17 days of abstinence. Across all points of abstinence, early-night slow-wave activity was associated strongly with non-deterioration of visual performance overnight. Furthermore, overnight enhancement of visual performance was predicted by the co-occurrence of sufficient early-night slow-wave activity and late night REM sleep, similar to results from studies in healthy subjects.
These results suggest that abstinence-associated sleep-dependent learning deficits are related to characteristic changes in sleep architecture, and promote the idea that treatments directed at sleep ('somno-tropic' treatments) could be helpful in offsetting physiological consequences of cocaine abstinence.
... 25 During the withdrawal phase, there is a decrease in sleep latency, an increase in total sleep time and sleep efficiency, and decreased ROL. 26,27 Patients experience a variety of sleep disturbances during cocaine withdrawal, including insomnia, hypersomnolence, and sometimes normalization of sleep in about 1 week. 25 Polysomnog-raphy may show an increase in stage N3 sleep and a decrease in REM sleep after cocaine use. ...
... 25 Polysomnog-raphy may show an increase in stage N3 sleep and a decrease in REM sleep after cocaine use. 26,27 There may be a progressive deterioration of sleep during abstinence. 25,28 Patients experience an increase in sleep latency and wake after sleep onset, decreases in ROL, total sleep time, and sleep efficiency, and a profound reduction in stage N3 sleep to the point of nonexistence. ...
A complex bi-directional relationship exists between substance use and sleep that encompasses several sleep disturbances including insomnia, hypersomnia, obstructive sleep apnea, and excessive daytime sleepiness. Substances of abuse produce their effect by acting on various receptor and neurotransmitter systems, some of which are involved in normal sleep regulation. Disruption of these neurotransmitter systems can lead to changes in the normal sleep architecture, causing sleep disturbances. Sleep disturbances can persist even after abstinence, a fact that is often not well recognized by substance use disorder treatment programs, and can lead to relapses. Incorporating strategies to counter sleep disturbances can help in relapse prevention. Pharmacologic and nonpharmacologic strategies exist that can be used to treat sleep disturbances in substance use disorders. The potential scope of these strategies is large, but currently there are limited data regarding which pharmacologic options are effective in treating sleep disturbances in patients with substance use disorders. Further advancement in the development of pharmacologic agents could lead to new strategies to help in relapse prevention and successful completion of substance use disorder treatment programs. This review explores the complex bi-directional relationship between substance use and sleep disturbances.
... When cocaine-dependent individuals attempt to quit using cocaine, they experience a number of withdrawal symptoms, including disturbances to sleep. During cocaine use, latency to REM sleep is increased, and total REM sleep is decreased (Watson et al., 1992). Then with abstinence REM rebounds (Watson et al., 1992). ...
... During cocaine use, latency to REM sleep is increased, and total REM sleep is decreased (Watson et al., 1992). Then with abstinence REM rebounds (Watson et al., 1992). During early (within one week of binge) abstinence, sleep efficiency, sleep latency, REM latency, and percent REM (Thompson et al., 1995;Johanson et al., 1999) are all improved. ...
Citicoline (cytidine-5'-diphosphate) is a mononucleotide composed of ribose, cytosine, pyrophosphate, and choline, and is involved in the biosynthesis of the structural phosopholipids of cell membranes. Treatment with citicoline, improves memory in patients with dementia, and reduces damage to the brain after traumatic brain injury or stroke. Recent research has been conducted to assess whether citicoline is an effective treatment for cocaine dependence. In cocaine-dependent individuals, withdrawal from cocaine is associated with disturbed sleep, which may contribute to the high rate of relapse to cocaine use. Therefore, it is important to know the impact of citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy.
In this double-blind, placebo-controlled trial, the effects of citicoline treatment on the sleep/wake cycles of cocaine dependent participants were assessed. The results of the current study are reported as part of a larger study, consisting of an eight-week treatment period to assess the efficacy of longer-term treatment with citicoline at decreasing cocaine consumption in cocaine-dependent polydrug using participants.
In this non-abstinent, cocaine-dependent population, citicoline had no effect on any of the sleep parameters measured including sleep efficiency, sleep latency, total sleep time, number of waking episodes, time awake per episode, amount of time in bed spent moving, number of sleep episodes, time asleep per episode, and amount of time in bed spent immobile.
These data suggest that eight weeks of citicoline administration does not disturb sleep/wake cycles of cocaine-dependent individuals.
... Dackis fluential studies of the subjective effects of cocaine withdrawal found that cocaine users reported poor sleep and fatigue in the first few days of abstinence but normal sleep shortly thereafter (10,11). However, small polysomnographic studies of sleep suggested that the sleep disturbance associated with abstinence from chronic use worsened rather than improved after initial abstinence (12)(13)(14)(15)(16)(17). In the largest polysomnographic study to date (18,19), using laboratory cocaine administration and an inpatient setting to confirm abstinence, we demonstrated that the quality of sleep, measured polysomnographically, deteriorates from the first to third week of abstinence, with characteristic alterations in sleep architecture. ...
... The changes in sleep architecture associated with chronic cocaine use include increases in sleep latency; decreases in total sleep time, slow-wave sleep time, and slow-wave activity; and alterations in REM sleep (12)(13)(14)(15)(16)(17)(18)(19)(20). These deficits are present initially and worsen over the course of 3 weeks of abstinence (18,19), without signs of improvement, and are associated with sleep-related cognitive deficits (18) that may be sleep-stage dependent Sl eep problems are a common and significant symptom of psychiatric illness (1). ...
The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users.
Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography.
Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness.
Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.
... The International Classification of Sleep Disorders (ICSD) provides a comprehensive classification system of sleep disorders, categorizing disorders into seven diagnostic sections: insomnia, sleeprelated breathing disorders, sleep-related movement disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, and other sleep disorders [36,37]. The revised edition of the ICSD also includes a separate International Classification of Diseases (ICD) code for substanceinduced sleep disorders in its appendices, which reflects clinical evidence indicating that drugs of abuse severely disrupt sleep [38,39] and that poor sleep is a risk factor for drug taking [40][41][42]. ...
It has been proposed that binge eating reflects a pathological compulsion driven by the “addictive” properties of foods. Proponents of this argument highlight the large degree of phenomenological and diagnostic overlap between binge eating disorder (BED) and substance use disorders (SUDs), including loss of control over how much is consumed and repeated unsuccessful attempts to abstain from consumption, as well as commonalities in brain structures involved in food and drug craving. To date, very little attention has been given to an additional behavioral symptom that BED shares with SUDs—sleep dysregulation—and the extent to which this may contribute to the pathophysiology of BED. Here, we review studies examining sleep outcomes in patients with BED, which collectively point to a heightened incidence of sleep abnormalities in BED. We identify the orexin (hypocretin) system as a potential neurobiological link between compulsive eating and sleep dysregulation in BED, and provide a comprehensive update on the evidence linking this system to these processes. Finally, drawing on evidence from the SUD literature indicating that the orexin system exhibits significant plasticity in response to drugs of abuse, we hypothesize that chronic palatable food consumption likewise increases orexin system activity, resulting in dysregulated sleep/wake patterns. Poor sleep, in turn, is predicted to exacerbate binge eating, contributing to a cycle of uncontrolled food consumption. By extension, we suggest that pharmacotherapies normalizing orexin signaling, which are currently being trialed for the treatment of SUDs, might also have utility in the clinical management of BED.
... Moreover, people who use illicit stimulants report mood alterations, both during the psychoactive period of use, and after long-term abstinence. Acutely, the use of illicit stimulants induces feelings of positivity, often characterised as euphoria (Ciccarone 2011), but after the acute intoxication period, users report negative feelings and depression, and in some extreme cases, suicidal ideation (Watson et al. 1992). Whilst the affective states produced by substances used for PCE may not be identical to recreational substance use, they have still been demonstrated to ameliorate aspects of self-reported mood during use (i.e., increases in interest and confidence) (Farah et al. 2009;Stoops et al. 2005). ...
... Sleep disturbances tend to normalize in about 1 week [21]. However, there may be persistent and progressive sleep disturbances in cocaine abstinence [22,23]. ...
... Ferner wachten die Probanden häufiger auf und klagten über eine reduzierte Schlafqualität [326]. Im Entzug kam es ferner zu einem vermehrten REM-Schlaf [327]. Infolge einer verminderten Schlafdauer und -qualität litten Stimulanzien-Konsumierende verstärkt unter Tagesmüdigkeit, dies wird in Verbindung mit kognitiven Störungen (siehe Abschnitt 6.11 Neurokognitive Störungen) gebracht [328][329][330]. ...
Background:
Addictive disorders form the group of the most common mental disorders. A wide range of psychotherapeutic treatment interventions exists; however, the proportion of patients receiving evidence-based interventions or psychotherapeutic treatment in outpatient care is very low.
Objective:
The aim of the present review was a systematic reassessment of the empirical evidence for the efficacy of the different forms of psychotherapeutic treatment, identification of new effective interventions and derivation of recommendations for treatment practitioners.
Material and methods:
A comprehensive literature search in a multistage method in the relevant national and international data banks was conducted. Subsequent analysis of topical guidelines, systematic reviews and original studies about addictions and therapy was performed.
Results:
A total of 3 topical national guidelines, 2 reviews and 16 original studies could be identified. In particular, cognitive behavioral therapy, behavioral interventions and motivational interventions could be identified as evidence-based interventions for the treatment of addictive disorders. Hypnotherapy can be recommended alternatively for patients dependent on tobacco. Also interesting for practitioners could be new treatment methods, such as neurocognitive training and mindfulness-based interventions.
Conclusion:
At present, although of high quality, results from existing studies are sometimes inconsistent or are numerically insufficient with respect to special treatment options. Future studies are warranted with respect to different substance use disorders and further patient groups.
... Although there have been several studies examining the acute effects of cocaine, another commonly used stimulant, on sleep using PSG (e.g., Post et al., 1974;Watson et al., 1992;Johanson et al., 1999), we are aware of only one PSG study that examined the effects of experimental methamphetamine administration on sleep (Miller et al., 1993). Miller and colleagues administered morning doses of oral methamphetamine to patients with narcolepsy and matched healthy controls. ...
Introduction
Use of amphetamine-type stimulants (e.g., methamphetamine) is associated with acute sleep disruptions. No prior reports have characterized the acute effects of methamphetamine on sleep using polysomnography, the gold standard for objective sleep monitoring.
Methods
Recreational stimulant users (n = 19) completed a baseline assessment, which included questionnaires assessing demographic and substance use characteristics, and the Pittsburgh Sleep Quality Index (PSQI), which assesses sleep quality over the past month. Participants were administered 0 mg (placebo), 20 mg, or 40 mg oral methamphetamine at 08:15 hours on study days, using a double-blind, randomized, within-subjects design. Sleep was monitored using polysomnography from 22:20 that evening until 06:15 the following morning.
Results
PSQI scores indicated more than half of participants reported poor sleep quality at baseline. Methamphetamine dose-dependently increased sleep latency, and decreased total sleep time, sleep efficiency, time in NREM 2 sleep, number of REM periods, and total time in REM sleep. Sleep under placebo conditions was consistent with what would be expected from healthy adults.
Conclusions
Morning oral administration of methamphetamine produces robust disruptions in nighttime sleep. Future research should examine relations between stimulant use and sleep disruption in naturalistic settings, with regard to both stimulant abuse and licit prescription use.
... During withdrawal, there is additionally more REM sleep [327]. As a result of diminished sleep duration and quality, stimulant users suffer from tiredness during the day, this was found to be linked to cognitive disorders (see Section 6.11 Neurocognitive disorders) [328][329][330]. It was shown that poor sleep quality was associated with more days of use per month. ...
Consumption of methamphetamine (“crystal”) has spread dramatically over several European countries. The management of methamphetamine-induced acute disorders has become a growing challenge to the health system. Pharmacological treatment strategies for methamphetamine-induced intoxication syndromes, acute withdrawal symptoms, and methamphetamine-induced psychosis are particularly important.
The development of interdisciplinary and evidence- and consensus-based (S3) German Guidelines was based on a systematic literature and guideline search on therapeutic interventions in methamphetamine-related disorders (April, June 2015). Consideration was given to 9 guidelines and 103 publications. Recommendations on pharmacological treatment strategies were drawn up using the nominal group technique.
Overall, only limited evidence is available. Benzodiazepines are first-line medication for methamphetamine-induced intoxication syndromes, particularly when they present with acute agitation and aggressive behavior. There is no evidence-based medication for the treatment of methamphetamine-related withdrawal symptoms and cravings. When treating methamphetamine-induced psychosis, second-generation antipsychotics should be favored, given their more favorable side-effect profile. The indication for continuation of antipsychotic medication must be reviewed regularly. In most cases, the antipsychotic should be tapered off within 6 months.
... The CSSA is a clinician-administered instrument that measures early cocaine abstinence signs and symptoms. The literatureinformed questions seek to quantify severity of symptoms that are most often associated with early cocaine abstinence, including depression, fatigue, anhedonia, anxiety, irritability, sleep disturbance, and inability to concentrate ( Brower et al., 1988 ;Cottler et al., 1993 ;Watson et al., 1992 ). Thus, similar to using the Beck Depression Inventory to quantify depression severity in patients with mood disorders, the CSSA provides a targeted quantification of anhedonia and depression in iCUD. ...
Background:
Hyposensitivity to non-drug reward, behaviorally manifested as anhedonia, is a hallmark of chronic substance use. Anhedonia is a transdiagnostic symptom underpinned by neurobiochemical disturbances in the reward circuit, yet an objective measure to assess anhedonia severity still eludes the field. We hypothesized that the Reward Positivity (RewP) component of the event-related potentials (ERPs) will specifically track anhedonia as the RewP is attributed to the same brain regions that are also implicated in anhedonia.
Methods:
Forty-six individuals with cocaine use disorders (iCUD) performed a gambling task predicting whether they would win or lose money on each trial, while ERP data was acquired. RewP in response to predicted win trials was extracted from the ERPs using the principal component analysis. State anhedonia and depression severity were assessed using the Cocaine Selective Severity Assessment (CSSA).
Results:
Although RewP amplitude correlated with both anhedonia and depression, only the RewP-anhedonia correlation survived a correction for depression severity. Further, a hierarchical multiple regression analysis revealed that anhedonia explained a significant amount of variance in the RewP amplitude, and this variance was significantly greater than that explained by demographics, severity and recency of drug use and even depression.
Conclusions:
These results show that RewP amplitude in response to rewarded trials tracks state anhedonia severity in iCUD. We argue that this association is perhaps driven by the activity in the dopaminergic mesocorticolimbic reward pathway that may underlie anhedonia symptomology as well as modulate RewP amplitude.
... Sleep continuity includes total sleep time, sleep latency, sleep efficiency, and wake after sleep onset, whereas sleep architectures include amounts of Stages 1-2 sleep and Stages 3-4 sleep (slow wave sleep, SWS), rapid eye movement (REM) sleep, and other REM measures (i.e., latency, density, and duration). Uncontrolled studies [5,[7][8][9][10][11][12], and a limited number of controlled studies [13,14] have examined PSG parameters during early abstinence in cocaine dependent subjects, and reported disturbances of sleep continuity (i.e., prolonged sleep latency; reduced sleep efficiency; and decreased total sleep time) as well as alterations in sleep architecture (i.e., increases in REM sleep, shortened REM latency) [4]. ...
Background and aims:
Sleep disturbance is a prominent complaint in cocaine and alcohol dependence. This controlled study evaluated differences of polysomnographic (PSG) sleep in cocaine dependent and alcohol dependent subjects, and examined whether substance dependence interacts with age to alter slow wave sleep and rapid eye movement (REM) sleep.
Design:
Cross-sectional comparison SETTING: Los Angeles and San Diego, California, USA.
Participants:
Abstinent cocaine dependent subjects (n = 32), abstinent alcohol dependent subjects (n = 73), and controls (n = 108); mean age 40.3 years, 91% male; recruited 2005-2012.
Measurements:
PSG measures of sleep continuity and sleep architecture primary outcomes of Stage 3 sleep and REM sleep. Covariates included age, ethnicity, education, smoking, body mass index, and depressive symptoms.
Findings:
Compared with controls, both groups of substance dependent subjects showed loss of Stage 3 sleep (p < 0.001). A substance dependence by age interaction was found in which both cocaine- and alcohol dependent groups showed loss of Stage 3 at an earlier age than controls (p < 0.05 for all), and cocaine dependent subjects showed loss of Stage 3 at an earlier age than alcoholics (p < 0.05). Compared with controls, REM sleep was increased in both substance dependent groups (p < 0.001), and cocaine and alcohol dependence were associated with earlier age-related increase in REM sleep (p < 0.05 for all).
Conclusions:
Cocaine and alcohol dependence appear to be associated with marked disturbances of sleep architecture, including increased rapid eye movement sleep and accelerated age-related loss of slow wave, Stage 3 sleep.
... Debe administrarlo un facultativo previamente familiarizado con la escala, la cual permite evaluar los signos y síntomas de abstinencia inicial de cocaína. Los 18 ítems que configuran esta escala describen los síntomas que se han asociado con más frecuencia a la abstinencia inicial de cocaína: depresión, fatiga, anhedonia, ansiedad, irritabilidad, trastornos del sueño e incapacidad para concentrarse (Dackis et al, 1987;Brower et al, 1988;Gawin y Ellinwodd, 1988;Watson et al, 1992;Cottler et al, 1993;Miller et al, 1993). Asimismo, la paranoia presentada con mucha frecuencia como síntoma de la abstinencia inicial de cocaína fue considerada como tal a partir de estudios llevados a cabo por Brower y Paredes (1987) y Gawin y Kleber (1986). ...
... It recurs approximately every 90 minutes and progressively increases its duration in consecutive sleep cycles. Several causes increase the percentage of REM or of the REM density during the night: first application of CPAP in patients with OSA [2], some stressful situations [14], depression [15], and withdrawal of substances suppressing REM, like alcohol [16], cocaine [17], or antidepressive drugs [18]. Among antidepressive drugs, the selective inhibitors of serotonin uptake (SSRI) decrease slow wave sleep and REM sleep and prolong REM sleep latency [19]. ...
A 20% increase in REM sleep duration has been proposed as a threshold to identify REM rebound in patients with obstructive sleep apnea (OSA) who start continuous positive airway pressure (CPAP) treatment. We describe the case of one patient with OSA who showed an unexpectedly high degree of REM rebound during titration of CPAP. A 34-year-old man was diagnosed with OSA. He remained untreated for many years, during which he developed systemic hypertension, depression, and severe daytime somnolence. When he was reevaluated sixteen years later, his Epworth sleepiness score was 18, and his OSA had greatly worsened (apnea/hypopnea index: 47, lowest nocturnal saturation: 57%). He underwent a successful CPAP titration during nocturnal polysomnography. Electroencephalographic analysis of the sleep recording revealed a huge amount of REM sleep, accounting for 72% of the total sleep time. When asked, the patient referred that he had suddenly interrupted paroxetine assumption three days before the polysomnography. The very large REM rebound observed in this patient could be due to additional effects of initiation of CPAP therapy and suspension of antidepressive treatment. This case does not report any dangerous consequence, but sudden antidepressive withdrawal could be dangerous for patients with OSA who develop hypoventilation during REM sleep with CPAP application.
... Schlafschwierigkeiten wurden häufig nach Kokainkonsum berichtet (Smith, Schwartz & Martin, 1989;Williamson et al., 1997). Polysomnographische (PSG-) Untersuchungen zeigen eine verlängerte Einschlafzeit, reduzierte Gesamtschlafzeit und supprimierten REM-Schlaf (REM = rapid eye movement) (Post, Gillin, Wyatt & Goodwin, 1974;Watson, Bakos, Compton & Gawin, 1992;Johanson, Roehrs, Schuh & Warbasse, 1999). ...
Fragestellung: Ziel ist die Darstellung des Einflusses von Drogen als stimulierende oder sedierende psychotrope Substanzen auf Änderungen im allgemeinen Wachheitszustand des Gehirns und auf die Schlaf-Wachregulation. Ergebnisse: Stimulanzien wie Kokain und Ecstasy (MDMA) führten zu einem gestörten Schlaf, während Cannabis und Benzodiazepine eher schlaffördernde Effekte hatten aber bereits bei mittelfristiger Gabe zu qualitativen Schlafveränderungen von funktioneller Relevanz führten. Obwohl keine illegalen Drogen im klassischen Sinne, weisen auch Benzodiazepine ein hohes Abhängigkeitspotenial auf, werden häufig missbräuchlich konsumiert, weshalb deren Effeke auf den Schlaf an dieser Stelle berichtet werden. Opioide wiederum hatten deutliche Schlafstörungen und eine Zunahme schlafbezogener Atmungsstörungen zur Folge. Einen gemeinsamen Effekt stellt die Suppression des REM-Schlafs dar. Als Entzugsphänomene traten häufig insomnische Beschwerden (Kokain, Cannabis, Benzodiazepine, Opioide), teilweise begleitet von einem REM-Rebound (Kokain, zumindest teilweise bei MDMA und Cannabis) auf. LSD beeinflusste die Schlafeffizienz wenig, führte aber auch zu Veränderungen des REM-Schlafs. MDMA-Opioid- und Benzodiazepin-Konsumenten zeigten oft Hangover-Effekte am nächsten Tag mit Tagesmüdigkeit, Konzentrations- und Leistungsdefiziten, vermehrten Stürzen und Verkehrsunfällen. Schlussfolgerungen: Die klinischen und therapeutischen Implikationen der beschriebenen Schlafveränderungen bleiben noch ungeklärt. Insbesondere mit dem Zusammenhang zwischen Insomnie, psychiatrischer und somatischer Komorbidität, Drogenkonsum und Rückfälligkeit werden methodisch belastbare Untersuchungen benötigt.
... While this study demonstrated that cocaine withdrawal is anxiogenic in nature, it is important to note that the reported withdrawal effects were devoid of somatic symptoms, such as: diarrhea, wet-dog shakes, weight loss, teeth chattering, tremors and convulsions (Wood and Lal, 1987). Clinical studies corroborated the existence of a cocaine withdrawal syndrome, characterized by anxiety and sleep disturbances (Gawin, 1991;Watson et al. 1992). Another classic example are the cannabinoids (e.g., marijuana), a drug class long thought to be devoid of withdrawal symptoms (Solomon and Corbit, 1974). ...
... Many of cocaine's effects on psychological functioning occur following withdrawal between administrations and include irritability, depression, insomnia and agitation. Psychological symptoms after chronic use include somatic complaints (Johanson et al., 1999;Watson et al., 1992), eating disorders (Ross-Durow and Boyd, 2000), anxiety, depression (Beckwith et al., 1999;Falck et al., 2002) and overall psychological distress post-partum (Singer et al., 1997(Singer et al., , 1995 and up to six years after (Minnes et al., 2008b). ...
Women who used cocaine during pregnancy may become at risk for increased physical and mental health problems.
Three hundred and twenty-one (158 cocaine use during pregnancy (PC), 163 no cocaine (NC)) women were assessed using the Health Survey Questionnaire (SF-36V2) 10 years after infant birth. Factors related to mental and physical health, and co-occurring with PC, were evaluated using multiple regression.
Controlling for age and education, PC women reported poorer total perceived mental health (PMH) (46.3±.9 vs. 50.7±.9, p<.001), more bodily pain (48.1±1.0 vs. 51.5±1.0, p<.02) and poorer health perceptions (46.8±.9 vs. 49.7±.9, p<.03) than NC women. PC women had lower BMI (29% vs. 32%, p<.006), higher current alcoholic drinks per/week (4.05±15.5 vs. 1.29±3.51, p<.005) and number of cigarettes per day (9±10.6 vs. 4±6.5, p<.0001) and greater total life strain (Family Inventory of Life Events and Changes (FILE)) (4.6±4.9 vs. 3.2±3.2, p<.004) than NC women. Regression analyses indicated that body mass index (BMI) mediated the effect of prior cocaine use on perceived physical health (PPH) and total life strain had additive effects. Current cigarette use and total life stress partially mediated the effects of cocaine use on PMH and also had additive independent effects.
PC use is a marker for poor health after 10 years. Mediators of these relationships (BMI, stressful life events and current tobacco use) should be considered when designing interventions to promote health.
... There are substantial individual differences in substance abuse patterns among cocaine users who present for treatment. Other studies have examined cocaine withdrawal after some regimen of controlled cocaine dosing, some as brief as a single dose (Foltin & Fischman, 1997; Johanson, Roehrs, Schuh, & Warbasse, 1999; McDougle et al., 1994; McDougle et al., 1992; Pace-Schott, Stickgold, Muzur, Wigren, Ward, Hart, Clark et al., 2005; Pace-Schott, Stickgold, Muzur, Wigren, Ward, Hart, Walker et al., 2005; Watson, Bakos, Compton, & Gawin, 1992). In one study (Foltin & Fischman, 1997), cocaine dependent subjects were allowed to self-administer up to twelve doses of 32 mg/70 kg intravenous cocaine per day over a two-or three-day " binge. ...
Cocaine withdrawal symptoms are thought to play a role in relapse; studies characterizing the symptomatology have yielded mixed findings. This study sought to examine the pharmacodynamic/pharmacokinetic profile of repeated high dose exposure to oral cocaine and characterize acute and protracted withdrawal in cocaine abusers. This study employed a repeated-dosing, single-blind design in which subjects (n = 9), resided for 40 days on a closed ward. They were maintained for two 4-day cocaine exposure periods (Days 1-4 & Days 9-12, cocaine 175 mg, p.o.; 5 hourly doses; 875 mg/day) separated by a 4-day matched placebo exposure period (Days 5-8). After these 12 days, an additional period of 28 days of placebo maintenance followed (Days 13-40). Test sessions were conducted during each phase; measures of mood, drug effects, sleep, pharmacokinetics, and prolactin were collected throughout the study. The dosing regimen produced cocaine plasma concentrations (Cmax of 680 ng/mL) two to threefold higher than typically seen in acute dose studies. Prototypic psychostimulant effects, including subjective ratings of euphoric effects (liking, high, good effects) and significant cardiopressor effects, were sustained during the active dosing periods, corresponding to the rise and fall of plasma cocaine. Withdrawal-like symptoms (i.e., disruptions of sleep, increased ratings of anxiety, irritability, crashing) were observed within 24-hr after cessation of dosing. Cocaine reduced prolactin acutely, but no sustained alterations were observed for this measure or for other signs or symptoms during the 28-day abstinence period. These findings indicate that exposure to controlled high doses of cocaine produces modest symptoms consistent with cocaine withdrawal within hours of cessation of dosing but provide no evidence of symptoms persisting beyond 24 hours.
... The identified drug-induced effects may therefore be important for the precipitation of short-term behavioral changes associated with cocaine withdrawal in animal models, such as decreases in locomotor activity and increases in anxiety levels (Fung and Richard, 1994), or more enduring responses associated with psychostimulant treatment such as behavioral sensitization (Kalivas and Alesdatter, 1993;Itzhak, 1997). In humans, such changes in glutamatergic function could play a role in the neurological, sleep, and mood impairments (O'Malley et al., 1992;Watson et al., 1992) observed in cocaine users and individuals experiencing withdrawal and related symptoms. ...
The present study characterized the effects of withdrawal from cocaine on the expression of NMDA receptor subunits (NR1, NR2B) and neuronal nitric oxide synthase. FosB induction was measured to confirm that repeated cocaine exposure influenced protein expression, as previously reported. Administration of cocaine followed by 24 h, 72 h, or 14 days of withdrawal resulted in alterations of NR1 and NR2B subunits and neuronal nitric oxide synthase expression as measured by immunohistochemical labeling of rat brain sections. Optical density analyses revealed significant up-regulation of NR1 in the ventral tegmental area at 72 h and 14 days of withdrawal. Structure-specific and withdrawal time-dependent alterations in NR2B expression were also found. After 24 h of withdrawal, cocaine-induced decreases in NR2B expression were observed in the nucleus accumbens shell, whereas increases in NR2B expression were found in medial cortical areas. Two weeks of withdrawal from cocaine caused an approximately 50% increase in NR2B subunit expression in regions of the cortex, neostriatum, and nucleus accumbens. In contrast, cocaine-induced up-regulation of neuronal nitric oxide synthase was transient and evident in cortical areas only at 24 h after the last drug injection. The results suggest that region-specific changes in interactions among proteins associated with the NMDA receptor complex may underlie neuronal adaptations following repeated cocaine administration.
In this article, we discuss the nature and treatment of insomnia in the context of common psychological comorbidities, including mood disorders, anxiety-related disorders, chronic pain, and substance-use disorders. We first review issues related to the diagnosis of insomnia when other psychological problems are present, and recent progression toward a more accurate understanding of the relation between sleep and psychological disorders. For each patient group discussed, we then provide a review of common sleep problems in the respective psychological problem, and discuss the current literature on insomnia treatment targets, insomnia treatment strategies, and insomnia treatment outcome data. We also discuss noteworthy insomnia treatment considerations for each patient population.
Dopamine, orexin (hypocretin), and adenosine systems have dual roles in reward and sleep/arousal suggesting possible mechanisms whereby drugs of abuse may influence both reward and sleep/arousal. While considerable variability exists across studies, drugs of abuse such as cocaine induce an acute sleep loss followed by an immediate recovery pattern that is consistent with a normal response to loss of sleep. Under more chronic cocaine exposure conditions, an abnormal recovery pattern is expressed that includes a retention of sleep disturbance under withdrawal and into abstinence conditions. Conversely, experimentally induced sleep disturbance can increase cocaine seeking. Thus, complementary, sleep-related therapeutic approaches may deserve further consideration along with development of non-human models to better characterize sleep disturbance-reward seeking interactions across drug experience.
Misuse of prescription medications has risen to popularity. Reasons for this practice include the self-medication of sleep and psychiatric disorders and attempts to counteract the dysphoric side effects of stimulant drugs. Clonazepam, a commonly prescribed benzodiazepine, has been increasingly used as a countermeasure to cocaine side-effects, including sleep reduction and anxiety. As both substances may impair sleep and aggravate psychiatric conditions, this study aimed to evaluate the long-term effects of the interaction of clonazepam and cocaine on anxiety-like behavior, and the short-term effects of this drug combination on sleep using male Wistar rats. Animals received saline, cocaine (15 mg/kg), clonazepam (1.25 mg/kg) or both drugs for 16 days. Sleep recording was performed on the first day of treatment to evaluate acute treatment effects. One day after the end of the treatment period, the open field and elevated plus-maze tests were used to assess anxiety-like behavior. Blood samples were collected for analysis of corticosterone levels. Rats receiving both drugs presented an increase in impulsivity when moving between arms in the elevated plus-maze and a reduction in exploratory behavior in the open field test. These findings suggest the presence of a withdrawal behavioral syndrome, which can manifest as a paradoxical increase in exploratory activity after a period without receiving the drug and may indicate the development of dependence. Combined treatment reduced paradoxical sleep time and increased its onset latency. There was no significant difference regarding corticosterone levels across any group. Our results contribute to the understanding of the risks of combining cocaine and clonazepam. Association of these drugs may impair sleep architecture and aggravate the dependence symptoms already seen when these substances are used separately. These findings may be useful in helping to counteract the impairments resulting from the combined use of these 2 substances and to raise awareness of these associated risks.
It is well-documented in the literature that individuals repeatedly exposed to cocaine exhibit cognitive impairment and that cognitive dysfunction is a risk factor for poor treatment outcomes in those with cocaine use disorder (CUD). Specific deficits related to attention, episodic memory, working memory, and executive functioning are the most common deficits noted in this population. Given that cognitive impairment is a risk factor for poor treatment outcomes in those with CUD, identifying possible moderating factors contributing to and/or exacerbating cocaine-related cognitive deficits is of great importance. Some of these factors may include premorbid intellectual functioning, cocaine use patterns, polysubstance use, comorbid emotional symptoms, and sleep dysfunction. It is plausible that by identifying moderating factors impacting cognition, behavioral interventions can then be modified accordingly and/or treatment regimens can be augmented with pharmacological interventions (e.g., cognitive enhancing agents), leading to a reduction in treatment attrition and improved treatment outcomes. The currently available treatments for CUD are mainly behavioral with variable efficacy, and even though there have been great preclinical and clinical research efforts focused on medication development for CUD, there are currently no Food and Drug Administration-approved medications for CUD. A description of some of the several potential moderating factors, along with some pharmacological treatments which have been shown to ameliorate, at least to some extent, cognitive dysfunction in those with CUD are discussed.
Das Ziel der Schadensminimierung („harm reduction“) besteht darin, das Ausmaß möglicher gesundheitlicher und psychischer Schäden durch den Methamphetamin-Konsum zu begrenzen. Adressaten sind alle Personen, die ihren Methamphetamin-Konsum nicht dauerhaft beenden wollen oder können.
A diagnosis of REM sleep behaviour disorder has important prognostic implications. The disorder is associated with synuclein-depositing neurodegenerative diseases and can be a harbinger of future decline and disability in those with these diseases.
Systematic observations of abuse and abstinence patterns that refine conceptualizations of street cocaine abuse and dependence are rare and, unfortunately, practical and ethical design restrictions on systematic inpatient research render clinical generalization from such studies negligible. Thus, a significant proportion of the clinical research base and clinical consensus is gleaned from experiences with heterogeneous “street” samples.
Design, Background and Pilot Data of Master Thesis. Please see the now available preprint:
https://www.biorxiv.org/content/early/2018/05/17/323667
Even if they do not complain, episodes of somnolence are frequent among alcoholodependant and drug addict patients. They can be related to the sedative effects of psychoactive substances (alcohol, opiates, cannabis) or the withdrawal of stimulants (tobacco, cocaine). They can also be related to the sleep disorders induced by the addictive substances. Lastly, they can be related to certain sleep disorders frequently found in addictions, in particular the sleep apnea syndrome and the syndrome of restless legs syndrome.
Definitions of dreaming are not required to map formal features of mental activity onto brain measures. While dreaming occurs during all stages of sleep, intense dreaming is largely confined to REM. Forebrain structures and many neurotransmitters can contribute to sleep and dreaming without negating brainstem and aminergic-cholinergic control mechanisms. Reductionism is essential to science and AIM has considerable heuristic value. Recent findings support sleep's role in learning and memory. Emerging technologies may address long-standing issues in sleep and dream research.
The Drugs of Abuse Conclusion Acknowledgments References
This paper reviews the recent literature supporting the hypothesis that reduced neurotransmission in the mesolimbic dopamine (DA) system may sustain some of the symptoms of depressive conditions including dysthymia. Experimental evidences indicate that mesolimbic DA plays a crucial role in controlling incentive, motivation and reward. Additionally, in different models of depression, a reduced DA activity in the limbic system, reversed by chronic antidepressant treatment, is observed. Finally, different antidepressants, irrespective of their acute action on the uptake of norepinephrine or serotonin, have the common property when given chronically to potentiate behavioural responses to DA agonists. The DA hypothesis of depression offers an explanation for the antidepressive effect of drugs such as sulpiride and amisulpride given at low doses, that preferentially block DA autoreceptors and thereby increase DA output.
This study attempted to clarify whether cocaine withdrawal altered sleep architecture and the role of adenosine receptors in this process. Cocaine (20 mg/kg) was administered subcutaneously once per day for 7 days to rat implanted with sleep/wake recording electrode. Polygraphic signs of undisturbed sleep/wake activities were recorded for 24 h before cocaine administration (basal recording as control); withdrawal-day 1 (after 1 day of repeated cocaine administration), withdrawal-day 8 (after 8 days of repeated cocaine administration), and withdrawal-day 14 (after 14 days of repeated cocaine administration), respectively. On cocaine withdrawal-day 1, wakefulness was significantly increased, total sleep was decreased, non-rapid eye movement sleep was markedly reduced, and rapid eye movement sleep was enhanced. Sleep/wake cycles were also increased on cocaine withdrawal day 1. However, non-rapid eye movement sleep was increased on withdrawal-day 8 and 14, whereas rapid eye movement sleep was decreased and no significant changes were observed in the total sleep and sleep/wake cycles during these periods. Adenosine A(2A) receptors expression was increased on withdrawal-day 8 and 14, whereas A(1) receptors levels were reduced after 14 days of withdrawal and the A(2B) receptors remained unchanged. Our findings suggest that alterations of sleep and sleep architecture during cocaine subacute and subchronic withdrawals after repeated cocaine administration may be partially involved in A(2A) receptors over-expression in the rat hypothalamus.
In earlier work REM sleep deprivation (RSD) by arousals improved endogenous depression. This suggested that drugs producing a similar RSD would have antidepressant activity. The arousal RSD was large, persisted for weeks, and was followed by a REM rebound. We call RSD with these properties arousal-type RSD. The present study reviewed literature from 1962 to 1989 on drug REM sleep effects to examine the hypothesis that drugs producing arousal-type RSD improve endogenous depression. The literature reviewed concerned the REM sleep effects of amine precursors, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, other hypnotics, drugs affecting cholinergic and noradrenergic neurotransmission, ethanol, lithium and narcotics. Four hundred and sixty-eight relevant papers were read and 215 contributed information that could be used in the review. The findings indicated that all drugs producing arousal-type RSD improved endogenous depression. Four drugs that improved endogenous depression did not produce arousal-type RSD.
Quantitative EEG changes were studied during cocaine withdrawal in 36 subjects. All subjects had used cocaine orally (n = 28) or intravenously (n = 8) within 48 h of admission to an inpatient unit. EEGs were recorded 2 and 6 days following admission. Nine subjects returned for a 1-month follow-up EEG. Modal EEG frequency significantly decreased on day 6 compared to day 2. The most dramatic change in both absolute and relative power from day 2 to day 6 was a decrease in the beta 2 (18-26 Hz) band. Those subjects who returned for the 4-week follow-up showed a further decrease in beta 2 power. Power in the beta 2 band was significantly greater for the intravenous users than for the smokers, and the decrease in power from day 2 to day 6 was also significantly greater in this group. While acute effects of cocaine on the EEG have been reported to last only several hours, this study indicates that chronic use may cause longer lasting neuroadaptive changes, particularly in those who have used cocaine intravenously.
Psychostimulant abusers often experience anhedonia, depression, fatigue, craving, and hypersomnia and increased propensity for rapid eye movement (REM) sleep during periods of acute and subacute withdrawal from cocaine and amphetamine. These signs and symptoms may reflect a state of relative functional dopamine depletion in the brain during abstinence. Lisuride, which has dopaminergic agonist effects, has been reported to reduce signs of psychostimulant withdrawal in rodent models of stimulant abuse. These observations prompted us to test the effects of oral administration of lisuride for 3 weeks (up to 4.0 mg daily) on mood and craving ratings in a double-blind, parallel design, controlled study in hospitalized stimulant abusers during acute withdrawal from cocaine or amphetamine. Although administration of lisuride significantly prolonged REM latency and reduced REM time, amelioration of other signs of withdrawal was not significantly greater in lisuride as compared with placebo treated patients. Self-rated craving ratings, however, were low in both groups throughout the hospital stay. Further studies, perhaps in patients with more severe symptoms during withdrawal, are needed to fully test the efficacy of lisuride in the treatment of stimulant withdrawal.
The proposed DSM-IV criteria for substance use disorders have included, as an option, a subtyping for physiologic dependence, characterized by either tolerance or withdrawal. Even if this option is not chosen at this stage of system revision, this weighting scheme justifies wider surveillance of these symptoms, especially for the more newly described cocaine dependence disorder. Wider surveillance of withdrawal is possible with the CIDI Substance Abuse Module (SAM), a WHO/ADAMHA diagnostic interview which covers criteria of substance use disorders according to the DSM-III, III-R, ICD-10 and proposed DSM-IV systems. To aid in this effort, we used the SAM, which includes a master list of all symptoms (n = 16) in the DSM manuals related to withdrawal from any substance to assess withdrawal symptoms from all substances. In this study, we hypothesized that the persons who used opiates with cocaine might misattribute their symptoms to cocaine; thus, we compared the responses of persons who used cocaine and opiates (opiate users) with the responses of persons who used cocaine without opiates (non-opiate users). Data from two St. Louis studies were combined for these analyses, users not in treatment or newly enrolled to drug-free or methadone treatment from a NIDA demonstration project and users selected for the St. Louis DSM-IV Field Trial. Of the 196 persons included from the field trial, 80% reported lifetime cocaine use compared with 91% of the 412 persons from the demonstration project. The symptoms mentioned in the diagnostic manuals were among the most frequently endorsed by both cocaine use groups.(ABSTRACT TRUNCATED AT 250 WORDS)
The new cocaine derivative CFT naphthalene sulphonate (WIN 35,428), has been shown to have a considerably longer duration of action and greater potency than cocaine as a central stimulant and it appears to have a similar mode of action on dopamine (DA) systems. The purpose of the present study was first to investigate the effects of low doses of WIM 35,428 with particular reference to the involvement of dopaminergic system in paradoxical sleep (PS), other sleep parameters and locomotor activity in the rat. WIN 35,428 a potent ligand of dopamine transporter showed biphasic effects upon PS and locomotor activity with low doses increasing and high doses decreasing PS. These changes reflect a functional involvement probably relevant to the action of Win 35,428 on DA transporters.
We hypothesized that stimulant abusers would sleep more and have more rapid eye movement (REM) sleep than primary alcoholics during acute withdrawal (first 10 days drug free) but would have opposite patterns during subacute withdrawal (days 11-14 drug free). We compared polygraphic sleep patterns during acute withdrawal (days 3-10) for 7 stimulant abusers and 8 alcoholics and during subacute withdrawal (days 11-14) for 7 different stimulant abusers and 8 different alcoholics. For comparison purposes, a group of normal controls from our preexisting database were matched for age and gender. Two statistically significant interactions were found: consistent with our hypothesis, stimulant abusers showed greater total sleep (TST) and REM sleep during acute withdrawal than subacute withdrawal, compared with alcoholics. In contrast, alcoholics showed less TST and REM sleep during acute withdrawal than during subacute withdrawal. Our polygraphic sleep data support the hypothesis that physiological withdrawal differs in alcoholics compared with stimulant abusers. Different mechanisms may underlie withdrawal in these two substances.
Dopamine has been proposed to mediate some of the behavioral effects of caffeine. This review discusses cellular mechanisms of action that could explain the role of dopamine in the behavioral effects of caffeine and summarizes the results of behavioral studies in both animals and humans that provide evidence for a role of dopamine in these effects. Caffeine is a competitive antagonist at adenosine receptors and produces a range of central and physiological effects that are opposite those of adenosine. Recently, caffeine has been shown to enhance dopaminergic activity, presumably by competitive antagonism at adenosine receptors that are colocalized and interact functionally with dopamine receptors. Thus, caffeine, as a competitive antagonist at adenosine receptors, may produce its behavioral effects by removing the negative modulatory effects of adenosine from dopamine receptors, thus stimulating dopaminergic activity. Consistent with this interpretation, preclinical behavioral studies show that caffeine produces behavioral effects similar to classic dopaminergically mediated stimulants such as cocaine and amphetamine, including increased locomotor activity, increased turning behavior in 6-hydroxydopamine-lesioned animals, stimulant-like discriminative stimulus effects, and self-administration. Furthermore, caffeine potentiates the effects of dopamine-mediated drugs on these same behaviors, and some of caffeine's effects on these behaviors can be blocked by dopamine receptor antagonists. Although more limited in scope, human studies also show that caffeine produces subjective, discriminative stimulus and reinforcing effects that have some similarities to those produced by cocaine and amphetamine.
A total of nine adult 'crack' cocaine users completed a protocol investigating changes in behavior on days following the self-administration of smoked cocaine. During self-administration sessions, participants could take up to six doses of smoked cocaine (50 mg; 25 mg for two participants). Both 2 and 3 day conditions were tested. During the 2 day condition, a cocaine self-administration session occurred in the afternoon and again in the evening on 2 consecutive days, while during the 3 day condition, self-administration sessions occurred twice a day-on 3 consecutive days. Participants reported greater cocaine craving (estimated using ratings of 'I want cocaine') and feeling more 'anxious,' 'confused,' 'of a good drug effect,' 'high,' 'sedated' and less 'friendly' the first day after using cocaine for 3 days compared to the first day after using cocaine for 2 days. Exposure to stimulus cues associated with smoked cocaine (e.g. participants preferred type of crack pipe) did not elicit cocaine craving or other behavioral changes after either 2 or 3 days of cocaine use. These data demonstrate that the cessation of heavy cocaine use under controlled laboratory conditions produced modest changes in mood and cocaine craving that were related to the length of the binge, and varied as a function of time since last cocaine use.
This article assesses the reliability and validity of the Cocaine Selective Severity Assessment (CSSA), a measure of cocaine abstinence signs and symptoms. Interrater reliability and scale internal consistency were high. Initial CSSA scores were significantly higher in cocaine-dependent subjects than in alcohol-dependent subjects. Initial CSSA scores were highly correlated with recent cocaine use and with severity measures from the Addiction Severity Index (ASI) including the interviewer severity rating and composite score in the drug section. Among cocaine-dependent subjects, initial CSSA scores were higher for those who failed to achieve abstinence or who subsequently dropped out of treatment. Further, CSSA scores showed consistent and marked declines over time for subjects who continued in treatment and remained abstinent. The CSSA appears to be a reliable and valid measure of cocaine abstinence symptoms and a useful predictor of negative outcomes in cocaine dependence treatment.
Sensationalism and shifting acceptance of drug use have influenced much of what has been written about cocaine. This review attempts a reasoned psychiatric appraisal of the prototypical abused psychomotor stimulants, cocaine and the amphetamines. We review the historical and epidemiologic features of the recent upsurge in cocaine abuse, summarize clinical psychiatric observations about stimulant abuse and emerging treatment approaches, and describe new perceptions of the biologic nature of stimulant addiction. Because emergency medical treatment of stimulant overdose and medical complications of cocaine and amphetamine abuse have been reviewed recently, we have excluded these topics.
Future sleep research in affective illness will probably continue the current evolution beyond cross-sectional to longitudinal studies, and beyond a largely descriptive emphasis to the testing of specific hypotheses and predictions derived from models of the pathophysiology of depression. These models are and will be variously neurochemical, chronobiological, genetic, and developmental in nature. Adequate testing of these models and predictions from them will require the use of pharmacologic and naturalistic probes and the use of sophisticated CNS imaging techniques. These probes will help further characterize the physiology of depression under conditions of disequilibrium or perturbation, such as following sleep deprivation, REM deprivation, phase advancement of the major sleep period, or the administration of antidepressant drugs with specific monoaminergic activity. Concurrently, if one is to understand further whether the sleep abnormalities of depression are part of a larger circadian rhythm disturbance, investigations will necessarily include 24-h measures of sleep-wake activity, psychomotor activity, and probably core body temperature rhythm under constant routine conditions. A complementary point of view would suggest that more intensive investigative efforts be focused on the first 100 min of sleep at night, since it is the first NREM-REM cycle that seems to show the greatest and most specific deviation in depressed patients from normal controls. Efforts to characterize further this part of the 24-h cycle, with respect to age- and gender-related variance as well as responses to physiologic, hormonal, pharmacologic, and naturalistic probes, are strongly warranted.
Abstinence symptoms and psychiatric diagnoses were evaluated in 30 chronic cocaine abusers. Structured diagnostic interviews were done within an experimental design intended to maximize differentiation of enduring symptoms from symptoms linked to binges of cocaine use. Longitudinal evaluations showed a three-phase sequence of post-cocaine abuse abstinence symptoms. Over half the sample also met criteria for ed 3 DSM-III, axis I psychiatric disorders. The findings present specific implications for treatment design.
The authors found that the clinical depressions which occurred following withdrawal from amphetamines after prolonged abuse were temporally associated with a decrease in the excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), a metabolite of norepinephrine, and altered EEG sleep patterns including an increased amount of D sleep (REM sleep). As the depressions subsided, MHPG excretion increased and measures of D sleep decreased.
Dependence on amphetamine, cocaine and other stimulants
- E H Ellinwood
Cocaine and other stimulants, A'. Engl
- F H Gawin
- E H Ellinwood