Post-traumatic stress disorder and sleep-what a nightmare!

According to DSM IV criteria, sleep disturbances are incorporated in the definition of post-traumatic stress disorder (PTSD). These include the re-experiencing symptoms (nightmares, criteria B) and a hyperarousal state (difficulty initiating and maintaining sleep, criteria D). PTSD patients commonly complain of sleep disturbances. Moreover, insomnia, restless sleep and trauma-related dreams might be the primary complaint of some patients. However, although subjective sleep disturbances are considered characteristic of PTSD, sleep laboratory studies have provided inconsistent evidence of objective sleep disorders. A variety of sleep architectures and sleep patterns has been reported in PTSD. However, only a few studies have controlled for comorbidities. Thus, uncertainty exists to what extent the sustained complaints of sleep disturbances in chronic PTSD are specifically related to the impact of exposure to traumatic stress, or rather are a consequence of comorbid disorders. Specific changes in REM sleep suggest a pathophysiologic role of REM sleep abnormality in PTSD (e.g. anxiety dreams, increased REM density, exaggerated startle response, decreased dream recall and elevated awakening thresholds from REM sleep). However, again, studies have failed to show consistent changes in percentage of REM sleep or in REM latency. There might be a coexistence of pressure to REM along with inhibitory forces of REM that result in high variability of REM parameters across patients. Alternatively, changes in REM sleep might reflect the effect of comorbid psychiatric disorders that results in inconsistent findings between patients. The current review tries to address these issues based on recent studies carried out in this field.     

Long-term neuropsychiatric consequences of "ecstasy" (MDMA): a review

The recreational drug "ecstasy" (3,4-methylenedioxymethamphetamine, or MDMA) is widely used by young people throughout the world. Experimental studies indicate that MDMA damages serotonergic neurons in animals and possibly in humans. Repeated use may induce long-term neurotoxic effects, with cognitive and behavioral implications. We reviewed both the preclinical and the clinical literature to assess the evidence for persistent neuropsychiatric sequelae in humans. We focused on studies of chronic recreational use and reports of presence or absence of neurological, psychiatric, and psychological problems related to MDMA exposure. These investigations show repeated use of ecstasy to be associated with sleep, mood, and anxiety disturbances, elevated impulsiveness, memory deficits, and attention problems, which may persist for up to 2 years after cessation. In a subset of humans, particularly adolescents, depletion of serotonin by MDMA use may hasten or enhance vulnerability to a wide array of neuropsychiatric problems. Together, the studies reviewed provide substantial evidence that MDMA causes neuronal damage in animals and humans. Additional research is necessary to determine whether the MDMA-induced destruction of serotonergic neurons can have long-term and possibly permanent neuropsychiatric consequences in humans.     

Sleep in Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is often associated with sleep disturbances. In this review, we focus on the published literature on subjective and objective findings of sleep in patients with PTSD. Insomnia and nightmares are most commonly reported subjective sleep disturbances. Polysomnographic investigations have frequently reported rapid eye movement (REM) sleep abnormalities in PTSD. However, studies have not been consistent about the type of REM sleep dysfunction in PTSD patients. Antidepressants such as nefazodone, trazodone, fluvoxamine, and imagery rehearsal therapy are found to be beneficial in the treatment of PTSD associated sleep disturbances as well as core symptoms of this anxiety disorder. We propose use of such modalities of treatment in PTSD patients with predominant sleep disturbances. Further studies are required to clarify polysomnographic sleep changes especially role of REM sleep dysregulation and treatment of sleep disturbances in PTSD.     

Neuroendocrine abnormalities in recreational ecstasy (MDMA) users: is it ecstasy or cannabis?

BACKGROUND: The purpose of this study was to investigate neuroendocrine function in ecstasy (3,4-methylenedioxymethamphetamine = MDMA) users and controls. METHODS: Prolactin response to d-fenfluramine was assessed in abstinent ecstasy users with concomitant use of cannabis only (n = 24, male/female 13/11) and in two control groups: healthy nonusers (n = 13, female) and exclusive cannabis users (n = 7, male). RESULTS: Prolactin response to d-fenfluramine was slightly blunted in female ecstasy users. Both male user samples exhibited a weak prolactin response to d-fenfluramine, but this was weaker in the group of cannabis users. Baseline prolactin and prolactin response to d-fenfluramine were associated with the extent of previous cannabis use. CONCLUSIONS: Endocrinological abnormalities of ecstasy users may be closely related to their coincident cannabis use. Cannabis use may be an important confound in endocrinological studies of ecstasy users and should be looked for more systematically in future studies.     

The marijuana withdrawal syndrome: Diagnosis and treatment

A subset of marijuana smokers develop a cannabis use disorder and seek treatment for their marijuana use on their own initiative. A less well-known consequence of daily, repeated marijuana use is a withdrawal syndrome, characterized by a time-dependent constellation of symptoms: irritability, anxiety, marijuana craving, decreased quality and quantity of sleep, and decreased food intake. Treatment studies show that rates of continuous abstinence are low (comparable to relapse rates for other abused drugs), and more treatment options are needed. The objective of this review is to update clinicians on the current state of marijuana research and to describe features of marijuana withdrawal to facilitate the diagnosis and treatment of cannabis use disorders.     

Are there sex differences associated with the effects of ecstasy/3,4-methylenedioxymethamphetamine (MDMA)?

Sex has been identified as an important factor in moderating the effects of several drugs of abuse. Given the increasing popularity of ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) use, it is important for researchers and clinicians to understand the factors that may influence its pharmacological actions to improve education, harm reduction and treatment efforts. This review focuses on preclinical and clinical research that examines the role of sex as an independent variable in the effects of ecstasy/MDMA. A systematic search of PsycINFO and MEDLINE electronic databases from 1966 to April 2006 was conducted. Both preclinical and clinical studies show a sexually dimorphic pattern in the acute, subacute and possibly long-term effects of ecstasy/MDMA. Specifically, adult females are more sensitive than males to the acute and subacute physical and psychological effects of ecstasy/MDMA and long-term alterations in aspects of 5-HT functioning. Conversely, males are more sensitive to the acute physiological effects of ecstasy/MDMA. These findings are consistent with research outcomes reported for other substances such as amphetamines and cocaine. Potential reasons for these sex differences and directions for future research are discussed.     

Sleep and Substance Use Disorders: An Update

Substance use disorders (SUD) are common and individuals who suffer from them are prone to relapse. One of the most common consequences of the use of and withdrawal from substances of abuse is sleep disturbance. Substances of abuse affect sleep physiology, including the neurotransmitter systems that regulate the sleep-wake system. Emerging research now highlights an interactive effect between sleep disorders and substance use. New findings in alcohol and sleep research have utilized sophisticated research designs and expanded the scope of EEG and circadian rhythm analyses. Research on marijuana and sleep has progressed with findings on the effects of marijuana withdrawal on objective and subjective measures of sleep. Treatment studies have focused primarily on sleep in alcohol use disorders. Therapies for insomnia in cannabis disorders are needed. Future research is poised to further address mechanisms of sleep disturbance in alcoholics and the effect of medical marijuana on sleep and daytime functioning.     

Association of paradoxical sleep deprivation and ecstasy (MDMA) enhances genital reflexes in male rats

Ecstasy ((±)3,4-methylenedioxymethamphetamine, MDMA) is a psychostimulant and a synthetic derivative of amphetamine that, according to its consumers, promotes the enhancement of sexual pleasure. This study sought to investigate the effects of ecstasy in the genital reflexes of paradoxical sleep deprived (PSD) male rats. Distinct groups of PSD rats were administered with saline or different doses of ecstasy. The incidence of genital reflexes was verified for 100 min. The four doses that were used induced genital reflexes in PSD animals and these significantly differed from their respective treated control groups. Under the influence of two intermediary doses (2.5 and 5 mg/kg), all animals displayed erection and ejaculation. The frequency of genital reflexes was also significantly greater than in relation to the PSD-saline group. The comparison between cocaine and ecstasy in PSD rats revealed that ecstasy induced more erections and ejaculations than cocaine. Thus, the present results showed a great enhancement of the genital reflexes of PSD rats that might have occurred due to serotoninergic alterations induced by this illicit substance when associated to sleep deprivation.     

REM sleep behavior disorder in Parkinson's disease and dementia with Lewy bodies

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia manifested by vivid, often frightening dreams associated with simple or complex motor behavior during REM sleep. Patients appear to "act out their dreams," in which the exhibited behaviors mirror the content of the dreams. Management of RBD involves counseling about safety measures in the sleep environment; in those at risk for injury, clonazepam and/or melatonin is usually effective. In this article, the authors present a detailed review of the clinical and polysomnographic features, differential diagnosis, diagnostic criteria, management strategies, and pathophysiologic mechanisms of RBD. They then review the literature and their institutional experience of RBD associated with neurodegenerative disease, particularly Parkinson's disease and dementia with Lewy bodies. The evolving data suggests that RBD may have clinical diagnostic and pathophysiologic significance in isolation and when associated with neurodegenerative disease.     

Major depression: the relative contribution of gender, MDMA, and cannabis use

Previous research has suggested that 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) users have elevated depressive symptomatology, although it is not clear whether this is due to MDMA or other drug use. This study aimed to investigate the contributions of MDMA and cannabis use to Major Depressive Disorder in MDMA users. A total of 226 MDMA users were studied. Participants (65% male) reported an average number of 35.8 uses of MDMA (SD = 45.6, range = 2-400). Participants were administered a Structured Clinical Interview for DSM-IV. Twenty-six individuals (11.5%) met lifetime criteria for Major Depressive Disorder. High rates of lifetime Cannabis Abuse (30.1%) and Cannabis Dependence (12.4%) were reported. No association was found between number of uses of MDMA and Major Depressive Disorder. Those with lifetime major depression were found, however, to have higher rates of lifetime cannabis use disorder (adjusted OR = 2.40). A logistic regression indicated that lifetime cannabis use disorder, but not MDMA use, was significantly associated with lifetime Major Depressive Disorder. Stratified analyses suggested that for males, neither drug use variable was associated with major depression. For females, a lifetime cannabis use disorder (adjusted OR = 4.99), but not MDMA use, was associated with lifetime Major Depressive Disorder. Results of this study suggest that although MDMA use was not found to be significantly associated with major depression for either gender, a lifetime cannabis use disorder was significantly associated with lifetime major depression for female, but not male, users of MDMA.     

Polysomnogram changes in marijuana users who report sleep disturbances during prior abstinence

BackgroundAbrupt discontinuation of heavy marijuana (MJ) use is associated with self-reports of sleep difficulty. Disturbed sleep is clinically important because MJ users experiencing sleep problems may relapse to MJ use to improve their sleep quality. Few studies have used polysomnography (PSG) to characterize changes in sleep architecture during abrupt abstinence from heavy MJ use.MethodsWe recorded PSG measures on nights 1, 2, 7, 8, and 13 after abrupt MJ discontinuation in 18 heavy MJ users residing in an inpatient unit.ResultsAcross abstinence, Total Sleep Time (TST), Sleep Efficiency (SEff), and amount of REM sleep declined, while Wake after Sleep Onset (WASO) and Periodic Limb Movements (PLM) increased. Furthermore, quantity (joints/week) and duration (years) of MJ use were positively associated with more PLMs.ConclusionThe treatment of sleep disturbance is a potential target for the management of cannabis use disorders since poor sleep could contribute to treatment failure in heavy MJ users.     

Dream experience during REM and NREM sleep of patients with complex partial seizures

This study examined the effectiveness of the cognitive processes underlying dreaming in patients with complex partial seizures (CPS), by assessing the frequency of recall and the structural organization of dreams reported after awakenings provoked alternately during REM and stage 2 NREM sleep on 12 cognitively unimpaired CPS-patients (six with epileptic focus in the right hemisphere and six in the left one). Each patient was recorded for three consecutive nights, respectively, for adaptation to the sleep laboratory context, for polysomnography and for dream collection. The frequency of dream recall was lower after stage 2 NREM sleep than REM sleep, regardless of the side of epileptic focus, while the length and structural organization of dreams did not significantly differ in REM and NREM sleep. However, the length of story-like dreams was influenced by global cognitive functioning during REM sleep. These findings indicate that in CPSs-patients the elaboration of dream experience is maintained in both REM and NREM sleep, while the access to information for conversion into dream contents and the consolidation of dream contents is much less effective during NREM rather than during REM sleep. Further studies may distinguish between these two possibilities and enlighten us as to whether the impaired memory functioning during NREM sleep is a side effect of anticonvulsant treatment.     

Idiopathic rapid eye movement sleep behaviour disorder

Neurological Sciences - Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by elaborate behaviours during REM sleep usually associated with action-filled dreams....     

Sleep architecture in stroke and relation to outcome

The aim of this study was to investigate sleep architecture in stroke patients, and correlate possible disturbances with the topography, severity and outcome of stroke and the presence of sleep-disordered breathing (SDB). In total, 62 acute stroke patients and 16 age- and gender-matched hospitalised controls underwent polysomnographic studies. Sleep architecture was analysed according to the topography of lesion, severity (National Institutes of Health Stroke Scale) and outcome (Barthel Index) of stroke. We found that sleep architecture is disturbed in stroke patients, regardless of SDB. Stroke patients (without SDB) have reductions in total sleep time and sleep efficiency, reduced stage II and slow wave sleep, increased wakefulness during sleep and increased sleep latency. Rapid eye movement (REM) sleep is reduced when SDB is also present. REM sleep is relatively preserved in cerebellar strokes, as opposed to other topographies. Sleep stages I and REM are negatively associated with stroke severity, and the latency to REM sleep is positively correlated with a good outcome. Sleep architecture is impaired in stroke patients (with fragmentation, increased wakefulness and reduced slow wave sleep), and this correlates with severity and outcome. Sleep disturbances should be investigated and addressed in these patients. Further studies are needed to confirm these findings and assess the clinical and therapeutic implications.     

Rapid Eye Movement Sleep Behavior Disorder

Abstract: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by loss of normal voluntary muscle atonia during REM sleep, and is associated with excessive motor activity related to dreaming. The movements are often potentially harmful and may lead to repeated injuries to the patients and/or their bedpartners.
RBD is more common in the elderly and affects predominantly males. A recent survey reported an estimated prevalence of RBD of 0.38% in the elderly and 0.5% in the general population. Because the treatment of RBD is effective and safe in most cases, awareness and diagnosis of RBD is critical. Overnight polysomnography is required to differentiate accurately between RBD and other sleep disorders, even though the patients have been clinically diagnosed as RBD according to the minimal criteria of the International Classification of Sleep Disorders. Muscle tone persists during REM sleep in RBD patients, and may be frequently augmented for prolonged periods of time. The density of REMs or phasic muscle activity occurring during REM sleep significantly increases in these patients, although their overall sleep architecture is usually normal, with the expected cycles of non-REM and REM sleep.
RBD occurs in both acute and chronic form. Acute cases are associated with intoxication and withdrawal. Chronic cases are most often either idiopathic or associated with neurological disorders—especially neurodegenerative diseases. The etiology of idiopathic RBD is still unknown, but a recent study has shown an association between some cases of idiopathic RBD and neurodegenerative disorders with parkinsonism such as Parkinson's disease, multiple system atrophy, and diffuse Lewy body disease. RBD patients thus need to be carefully followed up in terms of neurological evaluation.     

Physiology and psychology of dreams

The discovery of the close association between rapid eye movement (REM) sleep and dreaming and development of sleep laboratory techniques ushered in a new era in the study of dreams. For the first time, direct and systematic investigation could be made of such topics as the occurrence, qualities, recollection, and childhood development of dreaming. Experimental methodologies permitted investigation of the responsiveness of dreams to external stimulation and the effects of deprivation of REM sleep. Much effort was devoted to searching for parallels between physiological aspects of REM sleep and characteristics of associated dreams, with modest results. The leading theory of dreaming in the early decades of this research was the psychoanalytic, which views dreams as highly meaningful reflections of unconscious mental functioning. With developments in understanding of the neurophysiology of REM sleep, new theories of dreaming were proposed. The most prominent, the activation-synthesis hypothesis, derived its view of dreaming directly from the neurophysiology of REM sleep, in particular the role of the brain stem, and in its original form regarded dreams as not essentially meaningful. Further developments in neurobiological research, including lesion and brain imaging studies, have established a clearer view of the functional neuroanatomy of REM sleep and dreaming. To what degree, and in what way, implications can be drawn from these findings for the psychology of dreaming is controversial. Some more recent theories of dreaming emphasize an adaptive function related to emotion and a role in learning and memory consolidation.     

Cannabis withdrawal syndrome in patients with cannabis dependence only, and in patients with cannabis and opioid dependence

Background

The cannabis withdrawal syndrome occurs after cannabis cessation in more than 50% of dependent smokers. But although opioid-dependent patients are more frequently cannabis users and cannabis-dependent than the general population, the frequency and phenomenology of cannabis withdrawal symptoms in this specific population is unknown. Our hypothesis was that cannabis-dependent patients with current opioid dependence would experience the same withdrawal syndrome after cannabis cessation.

Objective

To describe cannabis withdrawal symptoms in cannabis-only dependent patients and in cannabis-dependent patients with current opioid dependence.

Methods

Using retrospective interviews, we evaluated the number and duration of six cannabis withdrawal symptoms in two groups: 56 cannabis-dependent patients without and 43 cannabis dependent patients with current opioid dependence. Cannabis and opioid dependence diagnoses were defined with DSM IV criteria using the MINI structured interview.

Results

The two groups were not different in terms of age of onset of cannabis use, and number of cannabis joints smoked at the time of the cannabis cessation attempt. The frequency of a cannabis withdrawal syndrome (defined as at least two different symptoms) did not differ in the two groups (65%). Neither was the proportion of subjects with the following symptoms: appetite or weight loss (30.8%), irritability (45.1%), anxiety (56%), aggression (36.3%) and restlessness (45.1%). Patients with cannabis dependence and current opioid dependence were more likely to report sleep disturbances (79.1 vs. 53.6%, chi² = 6.91, P = 0.007). The median duration of this cannabis withdrawal syndrome was 20 days post-cessation.

Conclusion

This is, to our knowledge, the first study describing cannabis withdrawal syndrome in cannabis-dependent patients with current opioid dependence. These patients experience a cannabis withdrawal syndrome as often as cannabis-only dependent subjects, but describe more frequently sleep disturbances. This high rate of sleep disturbances may cause relapse to cannabis use.