Betaine prevents and reverses the behavioral deficits and synaptic dysfunction induced by repeated ketamine exposure in mice.

As an N-methyl-D-aspartate (NMDA) receptor inhibitor, ketamine has become a popular recreational substance and currently is used to address treatment-resistant depression. Since heavy ketamine use is associated with persisting psychosis, cognitive impairments, and neuronal damage, the safety of ketamine treatment for depression should be concerned. The nutrient supplement betaine has been shown to counteract the acute ketamine-induced psychotomimetic effects and cognitive dysfunction through modulating NMDA receptors. This study aimed to determine whether the adjunctive or subsequent betaine treatment would improve the enduring behavioral disturbances and hippocampal synaptic abnormality induced by repeated ketamine exposure. Mice received ketamine twice daily for 14 days, either combined with betaine co-treatment or subsequent betaine post-treatment for 7 days. Thereafter, three-chamber social approach test, reciprocal social interaction, novel location/object recognition test, forced swimming test, and head-twitch response induced by serotonergic hallucinogen were monitored. Data showed that the enduring behavioral abnormalities after repeated ketamine exposure, including disrupted social behaviors, recognition memory impairments, and increased depression-like and hallucinogen-induced head-twitch responses, were remarkably improved by betaine co-treatment or post-treatment. Consistently, betaine protected and reversed the reduced hippocampal synaptic activity, such as decreases in field excitatory post-synaptic potentiation (fEPSP), long-term potentiation (LTP), and PSD-95 levels, after repeated ketamine treatment. These results demonstrated that both co-treatment and post-treatment with betaine could effectively prevent and reverse the adverse behavioral manifestations and hippocampal synaptic plasticity after repeated ketamine use, suggesting that betaine can be used as a novel adjunct therapy with ketamine for treatment-resistant depression and provide benefits for ketamine use disorders.

Trend level gene-gender interaction effect for the BDNF rs6265 variant on age of onset of psychosis.

A BDNF rs6265 [A/A] by gender by cannabis use interaction has been associated with age of onset of psychosis (AoP). We examined the gender and cannabis use-adjusted association between BDNF rs6265 [G>A] and AKT1 rs2494732 [T>C] and AoP. Data from 167 Caucasians on AoP and age at first regular cannabis use were collected. Kaplan-Meier and Cox regression analyses were conducted. A trend level gene-gender interaction effect was observed for the BDNF rs6265 A/A genotype, controlling for age at first regular cannabis use. Larger collaborative research projects are required to further investigate this effect.

Khat use and psychotic symptoms in a rural Khat growing population in Kenya: a household survey.

BACKGROUND: Khat is an amphetamine like psychostimulant chewed by over 10 million people globally. Khat use is thought to increase the risk of psychosis among its chewers. The evidence around this however remains inconclusive stemming from the scanty number of studies in this area and small study sample sizes. We undertook a large household survey to determine the association between psychotic symptoms and khat chewing in a rural khat growing and chewing population in Kenya. METHODS: For this cross-sectional household survey, we randomly selected 831 participants aged 10 years and above residing in the Eastern region of Kenya. We used the psychosis screening questionnaire (PSQ) to collect information on psychotic symptoms and a researcher designed sociodemographic and clinical questionnaire to collect information on its risk factors. We used descriptive analysis to describe the burden of khat chewing and other substance use as well as rates and types of psychotic symptoms. Using a univariate and multivariate analyses with 95% confidence interval, we estimated the association between khat chewing and specific psychotic symptoms. RESULTS: The prevalence of current khat chewing in the region was at 36.8% (n = 306) with a male gender predominance (54.8%). At least one psychotic symptom was reported by 16.8% (n = 168) of the study population. Interestingly, psychotic symptoms in general were significantly prevalent in women (19.5%) compared to men (13.6%) (p = 0.023). Khat chewing was significantly associated with reported strange experiences (p = 0.024) and hallucinations (p = 0.0017), the two predominantly reported psychotic symptoms. In multivariate analysis controlling for age, gender, alcohol use and cigarette smoking, there was a positive association of strange experiences (OR, 2.45; 95%CI, 1.13-5.34) and hallucination (OR, 2.08; 95% C.I, 1.06-4.08) with khat chewing. Of note was the high concurrent polysubstance use among khat chewers specifically alcohol use (78.4%) and cigarette smoking (64.5%). CONCLUSIONS: Psychotic symptoms were significantly elevated in khat users in this population. Future prospective studies examining dose effect and age of first use may establish causality.

Modulation of acute effects of delta-9-tetrahydrocannabinol on psychotomimetic effects, cognition and brain function by previous cannabis exposure.

Cannabis use has been associated with psychosis and cognitive dysfunction. Some evidence suggests that the acute behavioral and neurocognitive effects of the main active ingredient in cannabis, (-)-trans-Δ9-tetrahydrocannabinol (∆9-THC), might be modulated by previous cannabis exposure. However, this has not been investigated either using a control group of non-users, or following abstinence in modest cannabis users, who represent the majority of recreational users. Twenty-four healthy men participated in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject, ∆9-THC challenge study. Compared to non-users (N=12; <5 lifetime cannabis joints smoked), abstinent modest cannabis users (N=12; 24.5±9 lifetime cannabis joints smoked) showed worse performance and stronger right hemispheric activation during cognitive processing, independent of the acute challenge (all P≤0.047). Acute ∆9-THC administration produced transient anxiety and psychotomimetic symptoms (all P≤0.02), the latter being greater in non-users compared to users (P=0.040). Non-users under placebo (control group) activated specific brain areas to perform the tasks, while deactivating others. An opposite pattern was found under acute (∆9-THC challenge in non-users) as well as residual (cannabis users under placebo) effect of ∆9-THC. Under ∆9-THC, cannabis users showed brain activity patterns intermediate between those in non-users under placebo (control group), and non-users under ∆9-THC (acute effect) and cannabis users under placebo (residual effect). In non-users, the more severe the ∆9-THC-induced psychotomimetic symptoms and cognitive impairments, the more pronounced was the neurophysiological alteration (all P≤0.036). Previous modest cannabis use blunts the acute behavioral and neurophysiological effects of ∆9-THC, which are more marked in people who have never used cannabis.

Cocaine Abuse, Traumatic Brain Injury, and Preexisting Brain Lesions as Risk Factors for Bupropion-Associated Psychosis.

BACKGROUND AND OBJECTIVE: Bupropion is generally considered safe and is widely used both as a monotherapy and as an augmentation agent for the treatment of major depression. Concerns have been raised about bupropion's propensity to precipitate new psychosis and worsen existing psychotic symptoms, although the mechanism is poorly understood. Three cases are reported in which bupropion use was associated with psychosis. The aim of the study was to explore the risk factors and possible mechanisms of psychosis in each case. CASE REPORTS: Case 1 describes the interaction of cocaine abuse sensitization in a patient who developed psychosis with a lower dosage of bupropion. Cases 2 and 3 discuss the role of traumatic brain injury and structural brain lesions in increasing the risk of psychosis when using bupropion. CONCLUSIONS: Cocaine abuse, traumatic brain injury, and preexisting brain lesions appear to be risk factors for developing psychosis in persons taking bupropion. In such cases, clinicians should carefully assess the risks and benefits and closely monitor patients for symptoms of psychosis.

Are deficits in cognition associated with psychotic-like experiences after cannabis?

Not all individuals who smoke cannabis report psychotic-like experiences. Given that risk factors for psychotic disorders are multifaceted, precipitating factors to psychotic-like experiences after cannabis are likely to be equally complex. Reduced neurocognitive performance is associated with both psychosis risk and cannabis use. Therefore, it is possible cognitive performance may differentiate those who report psychotic-like experiences after cannabis from those who do not. We determined whether those reporting psychotic/dysphoric experiences after cannabis had reduced neurocognitive performance compared to those reporting primarily euphoric experiences. METHODS: Participants were recruited on the basis of responses to the cannabis high captured by the Psychosis-Dysphoric and Euphoric experiences subscales from the Cannabis Experiences Questionnaire (CEQ). RESULTS: Compared to participants reporting primarily euphoric cannabis experiences (n = 36; 44% male; mean age (SD) = 28 (9) years), those who reported psychotic/dysphoric experiences (n = 40; 45% male; mean age (SD) = 26 (5) years) demonstrated significantly faster responses to a trial and error learning task. In the presence of distracters, those with psychotic/dysphoric experiences after cannabis made more errors on a Continuous Performance Task. CONCLUSIONS: Those who report psychotic/dysphoric experiences after cannabis have subtle inefficiencies in their cognitive processes. The multiple factors which predict vulnerability to psychotic-like experiences after cannabis require further investigation.

Differential effects of sex on substance use between first episode psychosis patients and healthy people.

BACKGROUND: Substance use in psychosis is an important field of study given that it can be a risk factor for the development of psychosis and can give rise to psychotic symptoms. Studies of substance use in first episode psychosis patients do not frequently assess non-pathological substance consumption among patients, but rather the prevalence of substance abuse or dependence disorders. Moreover, most of these studies do not address the effects of sex in sufficient depth, and the consumption of caffeine or tobacco, which are two of the most frequently used substances, is often not assessed. OBJECTIVES: The aim of this study was to compare patterns and quantities of substance use between first episode psychosis patients and healthy controls and between men and women, and explore the potential interactive effects between group (patients or controls) and sex. METHODS: A total of 158 participants (82 first episode psychosis patients and 76 healthy controls) were included in the study. Both adults and adolescents were included in the study. Frequency and amount of use of caffeine, tobacco, alcohol, cannabis, cocaine, hallucinogens, stimulants, and opiates were gathered. RESULTS: A significant main effect of sex was found for the frequency of use of tobacco (p=.050). Main effects of group were found for the quantity of tobacco (p<.001) and cannabis (p<.001) consumed, as well as main effects of sex for the quantity of alcohol (p=.003) and cannabis (p=.017) consumed. There were also interaction effects between group and sex for the frequency of use of tobacco (p=.005) and cannabis (p=.009), and for the amount of cannabis consumed (p=.049). Qualitative differences between males and females regarding combined substance use are also reported. CONCLUSIONS: Among patients, men used tobacco more frequently than women, but this sex difference was not the same for the control group, in which women smoked more often than men. Regarding cannabis, men smoked cannabis more frequently and in larger amounts than women, but only in the patients group, whereas no sex differences for cannabis were found for the controls. Main effects of group and sex for tobacco and alcohol, as well as the lack of differences for the frequency and amount of use of caffeine, are also commented. This is the first study to assess the different effects of sex on substance use in first episode psychosis patients and healthy controls.

Adolescent Initiation of Cannabis Use and Early-Onset Psychosis.

BACKGROUND: It is important to evaluate the impact of cannabis use on onset and course of psychotic illness, as the increasing number of novice cannabis users may translate into a greater public health burden. This study aims to examine the relationship between adolescent onset of regular marijuana use and age of onset of prodromal symptoms, or first episode psychosis, and the manifestation of psychotic symptoms in those adolescents who use cannabis regularly. METHODS: A review was conducted of the current literature for youth who initiated cannabis use prior to the age of 18 and experienced psychotic symptoms at, or prior to, the age of 25. Seventeen studies met eligibility criteria and were included in this review. RESULTS: The current weight of evidence supports the hypothesis that early initiation of cannabis use increases the risk of early onset psychotic disorder, especially for those with a preexisting vulnerability and who have greater severity of use. There is also a dose-response association between cannabis use and symptoms, such that those who use more tend to experience greater number and severity of prodromal and diagnostic psychotic symptoms. Those with early-onset psychotic disorder and comorbid cannabis use show a poorer course of illness in regards to psychotic symptoms, treatment, and functional outcomes. However, those with early initiation of cannabis use appear to show a higher level of social functioning than non-cannabis users. CONCLUSIONS: Adolescent initiation of cannabis use is associated, in a dose-dependent fashion, with emergence and severity of psychotic symptoms and functional impairment such that those who initiate use earlier and use at higher frequencies demonstrate poorer illness and treatment outcomes. These associations appear more robust for adolescents at high risk for developing a psychotic disorder.

Early cannabis use is associated with severity of Cocaine-Induced Psychosis among cocaine smokers in Martinique, French West Indies.

OBJECTIVES: Cocaine intoxication can induce transient psychotic symptoms. The principal aim of this study was to determine sociodemographic and clinical characteristics associated with cocaine-induced psychosis (CIP) and to identify clinical factors predicting CIP in crack cocaine smokers in Martinique. The second aim was to identify clinical factors associated with severity of CIP, assessed with the Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis (SAPS-CIP). METHODS: Fifty-three cocaine-dependent smokers (45 men and 8 women) seeking treatment for cocaine dependence were included. Patients were assessed using the Cocaine Experience Questionnaire (CEQ), an instrument for the identification of cocaine-induced paranoia, and a French version of the SAPS-CIP, for the severity of CIP. RESULTS: Thirty-five (66%) patients reported cocaine-induced paranoia on the CEQ (CIP(+) patients). The mean SAPS-CIP total score was 6.1 ± 3.7, with a significant difference between CIP(+) and CIP(-) patients (P < 0.0001). Age at first cannabis use was associated with occurrence of CIP on the CEQ, and adolescent-onset cannabis use was associated with severity of hallucinations score on the SAPS-CIP. CONCLUSIONS: Cocaine-induced psychosis is frequent in crack cocaine smokers in Martinique, and early cannabis use is associated with the occurrence and the severity of psychotic symptoms during cocaine intoxication in this population. Patients developing psychotic symptoms during cocaine use began smoking cannabis earlier during adolescence than patients without CIP. These results confirm those of previous studies, highlighting the need to better assess early cannabis use in cocaine users, because early cannabis use is associated with severity of CIP.

Updating toxic psychosis into 21st-century Canadian: Bouchard-Lebrun v. R.

For centuries, Anglo-Saxon common law tradition has tended to limit voluntary intoxication as a defense on both mens rea (so-called diminished capacity defenses) and insanity. A new decision by the Supreme Court of Canada has clarified for Canadian jurisdictions whether voluntary substance-induced psychosis is a mental disorder for the purposes of determining insanity. In the United States, there is still considerable variation with regard to this question in such settled-insanity cases. This article is a review of Anglo-Saxon, American, and Canadian jurisprudence with regard to intoxication defenses on both mens rea and insanity. The factual and appellate history of Bouchard-Lebrun v. R. and a discussion of the Supreme Court's reasoning and the implications for future forensic practice follow. Potential pitfalls for forensic evaluators are explored, including the lack of scientific evidence available to detect individuals who, while appearing to present with a drug-induced psychosis, prove over time to have an endogenous psychotic illness.

New-onset psychosis following androgen deprivation therapy for prostate cancer.

Androgen deprivation therapy (ADT) is commonly used in the treatment of prostate cancer and is associated with several side effects including psychiatric disorders. We present an unusual case of a 62-year-old man with high risk prostate cancer that developed de novo psychosis after starting luteinizing hormone-releasing hormone (LHRH) agonists and discuss possible mechanisms to explain such findings. This case report highlights the importance of continuing assessment and monitoring of potential emotional and behavioral symptoms in prostate cancer patients treated with ADT.

"Spiceophrenia": a systematic overview of "spice"-related psychopathological issues and a case report.

OBJECTIVES: The use of synthetic cannabimimetics (SC; "spice" drugs) is increasing, especially among teenagers and young adults. In parallel with this, the number of studies describing intoxication episodes associated with psychotic symptoms in SC users is growing. We present both a systematic review of the related literature and a case report, which seems to highlight the existence of a possible association between SC use and psychosis. METHODS: Some 223 relevant studies were here identified and reviewed. Out of these, 120 full text articles were assessed for eligibility, and 41 were finally included in the systematic review. RESULTS: According to the available data from the studies here identified, SC's average age of users was 22.97 years, and the male/female ratio was 3.16:1. SC compounds most often reported in studies using biological specimen analysis were JWH-018, JWH-073, JWH-122, CP-47,497, and JWH-250. Mounting evidence seemed to suggest that psychotic symptoms such as hallucinations and delusions may occur in acute/chronic SC users. CONCLUSIONS: Although a clear causal link may not be here identified, the available evidence suggests that SC can trigger the onset of acute psychosis in vulnerable individuals and/or the exacerbation of psychotic episodes in those with a previous psychiatric history.

Self-inflicted testicular amputation in first lysergic acid diethylamide use.

BACKGROUND: Genital self-mutilation is a well-known phenomenon in patients with schizophrenia and has occasionally been described in patients with personality disorders or transsexuality. However, literature just provides few cases of genital self-mutilation related to the use of psychotropic substances. CASE DESCRIPTION: A previously mentally healthy man (age, 32 years) performed manual amputation of both testes after first use of lysergic acid diethylamide in combination with alcohol consumption. Follow-up examination 6 month after the event did not reveal the development of a psychiatric disorder. CONCLUSIONS: This report shows that a first and single use of lysergic acid diethylamide in combination with alcohol can cause intoxication with dramatic consequences.

[Can cannabis use increase the risk for schizophrenic psychoses?]. / Kann Cannabis das Risiko für schizophrene Psychosen erhöhen?

BACKGROUND: In recent years, cannabis has been increasingly discussed as one of the most important environmental risk factors for developing schizophrenic psychoses. This is mainly due to the following observations. (i) Cannabis at high doses can cause acute transient psychotic symptoms even in healthy individuals. (ii) Patients with schizophrenia abuse cannabis more often than age-matched healthy controls. OBJECTIVES: It is still controversial whether cannabis use can cause schizophrenic psychoses that would not have occurred otherwise. In our review, we have critically evaluated the evidence for a causal link between cannabis use and schizophrenic psychoses. METHODS: A systematic literature review in PubMed, ISI Web of Science and PsycINFO was carried out using the following keywords: cannabis, marijuana, THC, hashish, psychosis, schizophrenia. CONCLUSIONS: We have concluded that although a causal relationship between cannabis use and schizophrenic psychoses cannot be definitely proven, the available evidence strongly supports its plausibility. Furthermore, the results of the review indicate that cannabis might cause psychosis especially in individuals with a predisposition for schizophrenia and in adolescents with an early onset of cannabis use.

[Homicide and acute cortico-induced psychosis: A case report]. / Homicide et épisode psychotique aigu cortico-induit : à propos d'un cas.

BACKGROUND: Since their commercialization in 1950, the first psychiatric side effects of steroids have been reported. Today, steroids have become an important therapeutic tool in many diseases, but pharmacological mechanisms responsible for their side effects are still little known. The neuropsychiatric side effects concern 15% of patients while severe reactions occur in 5% of cases, mostly as acute psychotic episodes such as delusion. Serious forensic risks in this context are poorly documented and underestimated. CASE REPORT: We report the case of a 77 year-old man, treated by methylprednisolone for chronic lymphoid leukemia. After two months of treatment, although stabilized for the neoplastic disease, he stabbed his wife to death with a knife. In the emergency unit, an acute delirious state, a disorganization syndrome, and confusion items such as amnesia, disorientation and symptomatology fluctuation were observed. Mr. M also presented with hyponatremia and infectious pneumonia. Steroids were stopped and his condition rapidly declined, he died one month later during the hospitalization. DISCUSSION: This clinical case underlines the importance of the early detection of steroid psychosis and its management. Treatment should not be stopped brutally and a dose reducing strategy should be applied in combination with a mood stabilizer or antipsychotic treatment. Disease management strategies are insufficiently documented to be recommended. The extremely acute onset of the symptoms, a partial insight into delusions, a history of iatrogenic neuropsychiatry, the existence of somatic precipitating disorders and confusion factors should always alert the practitioner. The patient, and eventually his family circle, must be aware of the risks of adverse psychiatric effects of steroids for both ethical and forensic reasons, and must report them as early as possible to the clinician if they occur.

Does varenicline worsen psychiatric symptoms in patients with schizophrenia or schizoaffective disorder? A review of published studies.

OBJECTIVE: To review published cases and prospective studies describing the use of varenicline in patients with schizophrenia and schizoaffective disorder. DATA SOURCES: PubMed, PsychINFO, and the Cochrane Database were searched in July 2011 using the key words schizophrenia, schizoaffective disorder, psychosis, positive symptoms, negative symptoms, aggression, hostility, suicidal ideation AND varenicline to identify reports published between January 2006 and July 2011 in English. STUDY SELECTION: Five case reports, 1 case series, 1 retrospective study, 10 prospective studies (17 publications), and 1 meeting abstract describing the use of varenicline in patients with schizophrenia or schizoaffective disorder were identified. Review articles and articles describing findings other than the use of varenicline in patients with schizophrenia or schizoaffective disorder were excluded. Thirteen reports were included in the final analysis. DATA EXTRACTION: Information on each study's patient population, age, diagnosis, medication treatment, tobacco use history, adverse effects, and outcome was collected from the published reports. RESULTS: Of the 260 patients with schizophrenia or schizoaffective disorder who received varenicline in these published reports, 13 patients (5%) experienced the onset or worsening of any psychiatric symptom, although 3 of the 13 patients experienced a very brief negative effect after 1 dose. No patients experienced suicidal ideation or suicidal behaviors. CONCLUSIONS: Published reports suggest that, in most stable, closely monitored patients with schizophrenia or schizoaffective disorder, varenicline treatment is not associated with worsening of psychiatric symptoms. Current, prospective studies are assessing effectiveness and further assessing safety in this population.

A case of self amputation of penis by cannabis induced psychosis.

Self-mutilation, self-injuring or self-harming behaviour has been defined as deliberate destruction or alteration of body tissue in the absence of conscious suicidal intention. Persons suffering from mental disorder may inflict hundred of small wounds upon themselves which may be added to the actual cause of death. Another recognized syndrome is self mutilation of genitals almost invariably in males suffering from paranoid schizophrenia and often with strong religious flavour to their delusion. Here we present a case of a 35-year-old male who self mutilated his penis due to dependence on cannabis for the past few years that led to a condition called cannabis induced psychosis.

Acute mental disturbance caused by synthetic cannabinoid: a potential emerging substance of abuse in Hong Kong.

Synthetic cannabinoids are hybrid herbal/chemical products which mimic the effects of cannabis. They are usually marketed as incense or 'herbal smoking blend', and best known by the brand names 'K2' and 'Spice'. Their popularity among recreational drug abusers has grown rapidly due to their easy availability, relatively low cost, non-detection by conventional drug tests, and ease of concealing their use from family and authorities. They took Europe and later North America by storm in the late 2000s, yet limited medical literature exists detailing their adverse effects. They began to emerge in the Hong Kong drug scene in 2009. We report on a man who developed acute mental disturbance after 4 weeks of daily K2 abuse. This is the first case report of mental disorder caused by synthetic cannabinoid abuse in a Chinese.