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Illicit recreational drugs and sleep : a systematic review covering cocaine, ecstasy, LSD and cannabis

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Abstract

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.

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... Leider ist die Datenlage zu Studien zur Schlafbeeinflussung durch LSD sehr begrenzt (Schierenbeck, 2007). Nur wenige PSG-Untersuchungen mit begrenzter Fallzahl wurden durchgeführt, nutzen aber teilweise noch nicht die Schlafstadieneinteilung nach Rechtschaffen und Kales (1968). ...
... Die methodische Qualität vieler Arbeiten bleibt begrenzt, vor 1970 wurde noch nicht die heute anerkannte Einteilung der Schlafstadien nachRechtschaffen & Kales (1968) angewandt, teilweise wurde die PSG-Aufzeichnung ohne EMG und damit nur unsicherer Bewertung des REM-Schlafs durchgeführt. Generell sollten die Ergebnisse aus methodischer Sicht vorsichtig interpretiert werden, die Reproduktion ist teils gering (3 PSG-Studien zu LSD;Schierenbeck, 2007). Viele Untersuchungen wurden mit begrenzter Fallzahl und nur teilweiser Verblindung durchgeführt. ...
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The effect of d-lysergic acid diethylamide (LSD) upon ponto-geniculo-occipital (PGO) wave activity was studied in the cat. The results include the following observations: (1) During the acute phase of LSD's action (90–120 min), the PGO waves which appeared in the visual system were identical to those which normally accompany eye movement in the alert animal (PGOw). (2) A pattern of activity, not ordinarily present in the cortical EEG during arousal, began to dominate the recording in the intervals between PGOw as the dose of LSD was increased to a maximum of 800 . (3) A prolonged period of slow wave sleep followed the acute phase of drug action. There was a delay in the return of REM sleep and a delay in the appearance of the PGO waves associated with this state (Pgorem).The results oppose the hypothesis that the hallucinogenic effect of LSD is a result of the release of PGOREM into the state of wakefulness.
Article
The correlation between marihuana-induced aggressive behavior and changes in the sleep-wakefulness cycle was studied in chronically implanted rats. Marihuana injection in non-REM deprived rats did not induce aggressiveness irrespective of the animals being caged in isolation or paired. During this procedure quantization of the sleep-awake cycle revealed that wakefulness was increased while slow wave and REM sleep were decreased, mainly in the paired animals. REM deprived-marihuana injected animals recorded in isolation behaved like the control solution-injected rats. They showed a large rebound of REM and were not aggressive at the end of the 8 hr sessions. Conversely, when these animals were paired during the recording periods, they remained continuously awake and showed numerous episodes of aggressiveness. These results suggest that the aggressiveness inducing properties of marihuana are related to the REM deprivation and to the increased environmental stimulation achieved by pairing the animals.
Article
Cocaine in 6 mg/kg doses was administered orally and intraperitoneally to rats and sleep EEG's recorded. Cocaine significantly reduced total sleep time, slow-wave sleep, and sleep latency. Rapid eye movement sleep (REM) was significantly suppressed during the first half of the sleep recording. These effects were evident by both routes of administration. The effects of cocaine on total sleep time in animals parallels that observed in man.
Article
Effects of intravenous infusions of LSD (3.75, 7.5, 15 microgram/kg over 5 min; crossover N = 4) and tryptamine (0.04, 0.08, 0.12 mg/kg/min for 150 min; crossover N = 6) were compared to saline in intact cats through observation of five sleep/waking patterns. Electrocorticogram (ECoG) was analyzed for frequency band indices and mean amplitude and frequency. LSD increases wakefulness and drowsiness and decreases spindle sleep and rapid eye movement (REM) sleep during the first 75 min (period 1). The increase in active wakefulness and decrease in REM sleep persist during period 2, with an increase in spindle sleep thereafter. LSD increases delta index and ECoG amplitude, with a decrease in ECoG frequency; these effects peaked in period 2. Tryptamine increases wakefulness and drowsiness during period 1, with decreases in spindle sleep and REM sleep. The increase in quiet wakefulness and decrease in REM sleep persist during period 2, but no significant tryptamine effect is seen in sleep/waking patterns after infusion ceases. ECoG frequency increases during tryptamine infusion (periods 1 and 2), while ECoG amplitude increases during periods 2 and 3. Thus LSD and tryptamine both increase wakefulness, decrease spindle sleep, and decrease REM sleep.
Article
The actions of cannabidiol (CBD), one of the cannabis constituents, were assessed on the sleep-wakefulness cycle of male Wistar rats. During acute experiments, single doses of 20 mg/kg CBD decreased slow-wave sleep (SWS) latency. After 40 mg/kg SWS time was significantly increased while wakefulness was decreased. REM sleep was not significantly modified. Following the once-daily injections of 40 mg/kg CBD for a period of 15 days, tolerance developed to all the above-mentioned effects.
Article
Primary insomnia, major depression, and narcolepsy are usually considered to be separate disorders, distinguished by different polysomnographic profiles. But do polysomnographic data provide adequate evidence to segregate the three disorders, or might they display fundamentally the same sleep disturbance, differing only in degree? To test the viability of these two alternate hypotheses, the authors performed a meta-analysis of controlled polysomnographic studies of these disorders. A summary measure of degree of sleep disturbance was constructed from five variables: wakefulness after sleep onset, percentage of stage 1 sleep, percentage of stage 3 + 4 sleep, rapid eye movement (REM) latency, and REM density. The results of available studies for each variable were combined using a weighted average of effect sizes. An overall "sleep disturbance index" was then calculated by combining the estimates for the five above listed variables. On both the individual measures and especially on the summary index, insomnia, depression, and narcolepsy were arrayed on a simple continuum of progressively more severe sleep disturbance--congruent with the clinical observation that these disorders display progressively more disturbed sleep. These findings suggest that sleep can be disturbed in only a limited number of ways: in evaluating sleep architecture, it may not be possible to elaborate much beyond a single axis of good-to-bad sleep. Thus, polysomnographic measures may not provide adequate evidence to classify insomnia, depression, and narcolepsy as separate entities.
Article
The effect of cocaine on the behavioral state of six fetal sheep was studied during gestational ages between 128-135 days. Two to eight days after surgery, fetuses received either a continuous 60 min intravenous infusion of cocaine HCl (33.4 mg) or saline. The infusions were preceded and followed by control periods of 102 min. Cocaine induced a disruption in fetal behavioral state cyclicity and a decrease in the amount of time spent in rapid eye movement sleep (P < 0.01) and non-rapid eye movement sleep (P < 0.05) during the infusion, but not during the recovery period. Spectral amplitude of the electrocortical activity at all three cortical locations increased within most one-third octave bands between 0.8-4 Hz and decreased within most bands between 16-25 Hz (P < 0.05) compared to controls. There were no differences in spectral amplitude between pre- and post-cocaine periods at any location over the 25 frequency bands studied (P > 0.6) except for one frequency band centered at 12.5 Hz. The effects of a one hour cocaine infusion on fetal cortical electrical activity are diffuse, but short-lived, and occur independently of changes in fetal oxygenation.
Article
3,4-methylenedioxyethamphetamine (MDE; "Eve") exerts similar psychotropic effects in humans as 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and is less toxic in animal studies. We conducted a double-blind, placebo-controlled, cross-over sleep electroencephalogram (EEG) study with healthy volunteers. One hundred forty milligrams of MDE or placebo were administered PO in six subjects at 11 PM. Sleep EEG was registered from 11 PM-7 AM the next morning. All subjects had a normal sleep onset latency. They all awoke 60 to 120 min after administration of MDE and stayed awake for at least 150 min (total sleep time, TST MDE < placebo and intermittent time awake MDE > placebo: p < 0.001). After again falling asleep rapid eye movement (REM) sleep was totally suppressed (REM during time in bed, TIB MDE < placebo: p < 0.001). A cyclic alternation of relatively long periods of slow wave sleep (SWS) with periods of light sleep occurred in three subjects during the second part of the night (stage 4 in second part of night MDE > placebo: p = 0.16). The effects of MDE on sleep variables largely demonstrate the stimulant, amphetamine-like properties of MDE.
Article
We report on nine patients between the ages of 21 and 39 years who were admitted to an inpatient substance abuse treatment unit for cocaine treatment. The patients' sleep was studied in the laboratory for 4 nights during the first week, and 2 nights during the second and third weeks of their hospitalization. Daily mood ratings, cocaine craving scores and sleep logs were also recorded on each patient. During the first week of withdrawal, these patients had a markedly shortened REM latency, an increased REM sleep percentage, a very high REM density and a long total sleep period time. During the third week, REM latencies were very short and total percentage of REM sleep was increased. By week three of withdrawal the sleep continuity pattern was similar to that found in chronic insomnia, with a long sleep latency, an abnormally increased total time awake after sleep onset and a poor sleep efficiency. The subjects' ratings of cocaine craving, total POMS scores and depression fell precipitously after the first week of withdrawal and were at sub-clinical levels by week three of withdrawal.
Article
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.
Article
To evaluate cerebral cortical function with electroencephalography in infants of cocaine-addicted mothers. Patient series. The Children's Hospital of Philadelphia (Pa). Thirty-five consecutive infants of cocaine-addicted mothers hospitalized for a comprehensive health assessment and 51 healthy, age-matched infants studied with electroencephalography and respiratory thermistor because they were siblings of sudden infant death victims (comparison group). None. Behavioral states during spontaneous daytime sleep were classified as active sleep or quiet sleep; quiet sleep was further characterized as immature, tracé alternant sleep or mature, continuous, slow wave sleep. No episodes of ictal apnea or nonictal apnea were recorded in infants of cocaine-addicted mothers; nonictal apnea was observed in one control patient. No electrographic seizures were recorded. There were no significant differences between the proportions of infants exposed to cocaine in utero and that of controls who displayed excessive sharp electroencephalographic transients, background abnormalities, immaturity, and hypermaturity. Electroclinical sleep discordance was present in 5.7% of infants of cocaine-addicted mothers vs 0% of controls. Cocaine-exposed infants displayed mature, continuous, slow wave sleep below 45 weeks of conceptional age in a significantly higher percentage than those in the comparison group. Although frank electroencephalographic abnormalities were infrequent in infants whose mothers were addicted to cocaine, they differed significantly in their younger age of onset of continuous, slow wave sleep. Our findings provide continued reason for concern that infants of cocaine-addicted mothers may suffer subtle adverse neurologic, cognitive, or behavioral effects later in life. The longitudinal assessment of sleep disturbance and its relation to later development might permit tracking of the long-term effects of prenatal exposure to cocaine.
Article
Two persons are described who demonstrated prolonged neuropsychiatric syndromes after the ingestion of large doses of (+-)-3,4-methylenedioxymethamphetamine (MDMA), a recreationally used amphetamine analog. These cases suggest that MDMA, known to be neurotoxic to serotonin neurons in several experimental animals, may also produce untoward effects in humans. In addition, they provide evidence that ingestion of large doses of MDMA can produce lasting adverse functional consequences in vulnerable persons.
Article
In a sample of 298 cocaine abusers seeking inpatient (n = 149) or outpatient (n = 149) treatment, rates of psychiatric disorders were determined by means of the Schedule for Affective Disorders and Research Diagnostic Criteria. Overall, 55.7% met current and 73.5% met lifetime criteria for a psychiatric disorder other than a substance use disorder. In common with previous reports from clinical samples of cocaine abusers, these overall rates were largely accounted for by major depression, minor bipolar conditions (eg, hypomania, cyclothymic personality), anxiety disorders, antisocial personality, and history of childhood attention deficit disorder. Affective disorders and alcoholism usually followed the onset of drug abuse, while anxiety disorders, antisocial personality, and attention deficit disorder typically preceded drug abuse.