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The aim of the study is to discuss the use of crack in the form of "virado" as a harm reduction strategy in Pernambuco, Brazil. This is a cross-sectional study with a qualitative approach in which semi-structured interviews were conducted regarding aspects related to the culture of crack use with 39 crack users between March and August 2016. Participants were recruited using saturation criteria and data were analyzed through content analysis. Respondents discussed the use of "virado" and compared its effects in relation to crack, addressing improvement in interpersonal relationships, libido, and non-compulsive drug use, which can all be understood as harm reduction strategies. On the other hand, equipment sharing for the use of "virado" was identified as a high-risk practice with regards to the transmission of infectious diseases. Knowing about the culture of crack use in different contexts is essential in order to plan and develop health care actions.

Objective: To evaluate the effectiveness and tolerability of brivaracetam (BRV) in a refractory epilepsy population in an outpatient clinical setting., Methods: Retrospective medical information system review and self-report questionnaire for all patients treated with BRV until the end of 2017., Results: Thirty-eight patients were included, 73.7% female and mean age 36.2. The mean number of antiepileptic drugs (AEDs) for previous use was 8.9, and for current use was 2.5. Mean seizure frequency in the last 3 months was 12 per month. At 3, 6, 12, and 15 months, the 50% responder rates were 36.1%, 32%, 41.2%, and 45.5%, respectively. Patients took BRV for a median duration of 8.25 months, ranging from 7 days to 60 months. Retention rate was 75.0%, 72.0%, 59.2%, and 47.9% at 3, 6, 12, and 15 months, respectively. Overall, the main reasons for discontinuation were adverse events (AEs) (52.3%), lack of efficacy (35.3%), or both (11.8%). The rate of total AEs was 60.5% according to medical records and 85.7% according to questionnaire, including mostly tiredness, psychiatric, and memory complaints. Psychiatric side effects occurred in 31.6% according to medical records and 47.4% according to questionnaire results, which is higher than previously reported and persisted throughout the study period., Conclusions: BRV appears to be a useful and safe add-on treatment, even in a very refractory group of patients. In this real-life clinical setting, psychiatric AEs were found at a higher rate than previously published.

Background: There is evidence that schizophrenia is a neuro-immune disorder. Genes linked to intragenic LINE-1 methylation show a strong association with immune-associated disorders including psychosis. The aim of this study was to examine LINE-1 methylation patterns in paranoid schizophrenia and methamphetamine-induced paranoia, a model for schizophrenia., Methods: This study recruited 31 patients with paranoid schizophrenia, 94 with methamphetamine-induced paranoia (MIP) and 163 normal controls. LINE-1 methylation patterns were assayed in peripheral blood mononuclear cells and a combined bisulphite restriction analysis and COBRA were used to estimate LINE1 methylation (mC) and CpG dinucleotide methylation patterns, namely 2 methylated (mCmC) and 2 unmethylated (uCuC) CpGs and the partially methylated loci mCuC (5'm with 3'u) and uCmC (5'u with 3'm)., Results: Patients with paranoid schizophrenia show highly significant changes in LINE-1 partial methylation patterns, namely a higher percentage of mCuC and lower percentage of uCmC as compared with controls and MIP patients, while the latter show a higher percentage of mCuC but lower percentage of uCmC as compared with controls. Higher mCuC significantly predicts paranoid schizophrenia with a sensitivity of 51.6%, specificity of 97.5% and an area under the ROC curve of 0.895., Conclusions: The results indicate that a common dysfunction in LINE-1 partial methylation may underpin both paranoid schizophrenia and MIP and that this methylation pattern is significantly more expressed in paranoid schizophrenia than MIP. Reciprocal links between impairments in LINE-1 methylation and neuro-immune and neuro-oxidative pathways may underpin the pathophysiology of both MIP and paranoid schizophrenia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Objectives: Synthetic cannabinoid use is associated with severe problems, including psychosis, kidney failure, and death. Given that young adults are especially vulnerable to using synthetic cannabinoids, the current study sought to identify factors and consequences related to use within this population., Methods: 1140 undergraduates completed an online survey of synthetic cannabinoid use, consequences, and related constructs., Results: The prevalence of lifetime synthetic cannabinoid use was 7.9% (n = 90), 15.6% (n = 13) of which were regular users, meaning they used once a year or more often. Synthetic cannabinoid users reported multiple adverse effects (e.g., anxiety, paranoia, tachycardia, lightheadedness) and 16.7% (n = 15) of users said they considered or did go to the Emergency Room while using synthetic cannabinoids. In the entire sample, participants believed their friends (t = 18.3, p < .001) and students in general (t = 46.0, p < .001) use synthetic cannabinoids more than they do. Natural cannabis users were associated with increased odds of having tried synthetic cannabinoids than those who had never used natural cannabis, OR = 7.63 (4.44 to 13.14) p < .0001, and 92.2% (n = 83) of synthetic cannabinoid users reported lifetime use of natural cannabis. Common reasons for use were legality, not appearing on drug tests, and availability, not that students enjoyed using synthetic cannabinoids or thought they were safe to use., Discussion and Conclusions: Synthetic cannabinoid use is associated with a variety of negative consequences. The data also supports a strong link between natural cannabis use and synthetic cannabinoid use., Scientific Significance: Natural cannabis users appear to be a high-risk group for using synthetic cannabinoids. There are multiple negative effects associated with synthetic cannabinoid use and reasons for use relate to convenience vs. enjoyment. Data have important implications for prevention and treatment efforts., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The use of psychoactive substances, including methamphetamine (MA) may cause changes in DNA methylation. The aim of this study was to examine the effects of MA use on long interspersed element-1 (LINE-1) methylation patterns in association with MA-induced paranoia. This study recruited 123 normal controls and 974 MA users, 302 with and 672 without MA-induced paranoia. The Semi-Structured Assessment for Drug Dependence and Alcoholism was used to assess demographic and substance use variables. Patterns of LINE-1 methylation were assessed in peripheral blood mononuclear cells and a combined bisulfite restriction analysis (COBRA) was used to estimate overall LINE-1 methylation (mC) while COBRA classified LINE-alleles into four patterns based on the methylation status of two CpG dinucleotides on each strand from 5' to 3', namely two methylated (mCmC) and two unmethylated (uCuC) CpGs and two types of partially methylated loci (mCuC that is 5'm with 3'u and uCmC that is 5'u with 3'm CpGs). MA users showed higher % mCuC and % mCuC + uCmC levels than controls. Use of solvents and opioids, but not cannabis and alcohol dependence, significantly lowered % uCmC levels, while current smoking significantly increased % uCuC levels. MA-induced paranoia was strongly associated with changes in LINE-1 partial methylation patterns (lowered % uCmC), heavy MA use, lower age at onset of MA use, and alcohol dependence. Women who took contraceptives showed significantly lower LINE-1 % mC and % mCmC and higher % uCuC levels than women without contraceptive use and men. The results show that MA-induced changes in LINE-1 partial methylation patterns are associated with MA-induced paranoia and could explain in part the pathophysiology of this type of psychosis. It is argued that MA-induced neuro-oxidative pathways may have altered LINE-1 partial methylation patterns, which in turn may regulate neuro-oxidative and immune pathways, which may increase risk to develop MA-induced paranoia.

A dopamine excess is thought to be involved in positive psychotic symptoms in schizophrenia. All current antipsychotics show a degree of dopamine receptor antagonism. Little is known about the differential effectiveness of different antipsychotics in treating specific sets of symptoms. We report the case of a 35-year-old man with schizophrenia who presented with prominent hallucinatory symptoms (Positive and Negative Syndrome Scale [PANSS] P1=5, P3=5, P6=5) resistant to high doses of a dopamine, serotonin receptor antagonist, olanzapine. Switching from olanzapine to zuclopenthixol, a dopamine D2 receptor antagonist, led to a complete shift of his symptomatology: his hallucinations abated, however, he presented as very highly paranoid (PANSS P1=6, P3=2, P6=7). On a combination of both antipsychotics, his symptoms subsided (PANSS P1=3, P3=2, P6=2). We discuss the potential for differential effectiveness of different antipsychotic medications in treating hallucinations and paranoia. We argue that future studies could address this question by stratifying patients based on symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess prospectively the prevalence of impulse control disorders (ICD), psychiatric symptoms, and their clinical correlates in patients with prolactinoma receiving dopamine agonists (DA) in comparison to those with non-functioning pituitary adenomas (NFA) and healthy controls (HC)., Methods: A total of 25 patients with prolactinoma, 31 with NFA, and 32 HCs were included in the study. All patients and controls were screened for the presence of ICDs and other psychiatric disorders using revised version of Minnesota Impulsive Disorders Interview (MIDI-R), Barratt Impulsiveness Scale (BIS-11), Symptom Check List (SCL-90-R) questionnaire and Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI)., Results: We detected two new cases (8%) of ICD associated with DAs. Both cases presented with hypersexuality, which reversed totally or decreased upon discontinuation of the drug. The re-challenge of the DA in a smaller dose has led to either no symptoms or weaker symptoms than before. There was an increase in the number of patients who screened positive on obsession, interpersonal sensitivity, paranoid ideation, and additional items subscales of SCL-90-R in comparison to HCs at the end of the study period (p < 0.05 for all). Likewise, cumulative DA dose was positively correlated to obsession, interpersonal sensitivity, paranoid ideation, hostility, phobic anxiety subscales, and GSI scores of SCL-90-R (p < 0.05 for all)., Conclusions: DAs are associated with a small but substantial short-term risk of ICD development and a broad range of psychiatric symptoms in patients with prolactinoma receiving DAs.

Background and Aims: To review early case reports and experimental inductions of amphetamine and methamphetamine psychosis, prior to the prohibition of these drugs, to gain a better understanding of the nature and aetiology of methamphetamine psychosis., Methods: Papers considered were historical case reports and case series of psychosis relating to the use and misuse of prescription amphetamine, focusing upon papers by Young & Scoville (1938), Connell (1958), and three subsequent experimental studies published in the early 1970s (Griffith 1972, Angrist & Gershon 1970 and Bell 1973), where psychosis was induced in volunteers using high-dose amphetamine and methamphetamine., Results: High-dose methamphetamine and amphetamine can result in a paranoid psychosis which remits rapidly (within days) of discontinuing use. The central feature is paranoia occurring in a clear state of consciousness. This may be accompanied by other psychotic symptoms (e.g. hallucinations). Pre-existing schizophrenia is not necessary, and the syndrome is not due to sleep deprivation., Conclusions: Research findings from the 1930s to the 1970s suggest that paranoid psychosis should be considered a probable consequence of high-dose methamphetamine use. Individuals who experience psychotic symptoms for any substantive period after intoxication has ended should be suspected of having a functional non-organic psychosis, or a latent vulnerability thereto., (© 2018 Society for the Study of Addiction.)

Introduction: Mocarz is a Legal high that consists of dried parts of plants mixed with synthetic cannabinoids. There is currently limited information on its acute toxicity., Case Report: We describe a 35-year-old patient with no previous medical and psychiatric history who was admitted to the psychiatric clinic after developing agitation and paranoid psychotic symptoms following the use of Mocarz purchased over the internet., Conclusion: Legal highs are a challenge in psychiatric acute care, because they provoke unpredictable mental states endangering self and others., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose of Review: Amphetamine-type stimulants now rank second worldwide in the table of most widely used recreational drugs. Many countries report increased availability and increased purity of the drugs.Surprisingly, while many authors in the last decade have described clinical issues and demographic patterns associated with amphetamine use, there is little published research quantifying the specifics of the impact of 'ICE' use on health resources.It is, therefore, timely to review the available literature on the impact of this group of drugs on emergency medical systems., Recent Findings: Recent research has focused on the increase in production and availability of metamphetamines. Clinical findings at acute presentation and long-term sequelae have been studied and in particular, the impact of the drugs on mental health and development of long-term neurological problems. Work has also been done unsuccessfully to develop therapeutic agents for the acute management of patients who present under the influence of amphetamines., Summary: It is clear that the use of metamphetamine-type substances places an increasing burden on acute health services. There is a need for preventive and harm-minimization strategies.

Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Aims: To explore the clinical features of methamphetamine-induced paranoia (MIP) and associations between MIP and a genetic polymorphism in dopamine β-hydroxylase (DBH-1021C→T)., Design: Retrospective analysis of clinical presentation and genetic association by χ(2) test and logistic regression analysis., Setting: A Thai substance abuse treatment center., Participants: A total of 727 methamphetamine-dependent (MD) individuals., Measurements: Clinical: Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) and the Methamphetamine Experience Questionnaire (MEQ). Genetic: DBH-1021C→T., Findings: Forty per cent of individuals (289 of 727; 39.8%) with MD had MIP. Within-binge latency to MIP onset occurred more rapidly in the most recent compared with initial MIP episode (P = 0.02), despite unchanging intake (P = 0.89). Individuals with MIP were significantly less likely to carry lower (TT/CT) compared with higher (CC) activity genotypes (34.3 versus 43.3%; χ(2) 1  = 5, P = 0.03). DBH effects were confirmed [odds ratio (OR) = 0.7, P = 0.04] after controlling for associated clinical variables (MD severity, OR = 3.4, P < 0.001; antisocial personality disorder, OR = 2.2, P < 0.001; alcohol dependence, OR = 1.4, P = 0.05; and nicotine dependence, OR = 1.4, P = 0.06). TT/CT carriers were more likely to initiate cigarette smoking (OR = 3.9, P = 0.003) and probably less likely to be dependent on alcohol (OR = 0.6, P = 0.05)., Conclusions: Among methamphetamine-dependent individuals, paranoia appears to occur increasingly rapidly in the course of a session of methamphetamine use. Severity of methamphetamine dependence and antisocial personality disorder predicts methamphetamine-induced paranoia. The genetic polymorphism in dopamine β-hydroxylase is associated with methamphetamine-induced paranoia and influences smoking initiation., (© 2014 Society for the Study of Addiction.)

We report a genome-wide association study (GWAS) for cocaine dependence (CD) in three sets of African- and European-American subjects (AAs and EAs, respectively) to identify pathways, genes and alleles important in CD risk. The discovery GWAS data set (n=5697 subjects) was genotyped using the Illumina OmniQuad microarray (8 90 000 analyzed single-nucleotide polymorphisms (SNPs)). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4063 subjects. Then, the most significant GWAS SNPs were genotyped in 2549 independent subjects. We observed one genome-wide-significant (GWS) result: rs2629540 at the FAM53B ('family with sequence similarity 53, member B') locus. This was supported in both AAs and EAs; P-value (meta-analysis of all samples)=4.28 × 10(-8). The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 2) SNP rs150954431 was associated with P=1.19 × 10(-9) in the EA discovery sample. SNP rs2456778, which maps to CDK1 ('cyclin-dependent kinase 1'), was associated with cocaine-induced paranoia in AAs in the discovery sample only (P=4.68 × 10(-8)). This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies.

Purpose: The purpose of this review is to heighten the awareness of the increased use and risks of synthetic cannabinoids (SCs) and associated clinical manifestations among adolescents and young adults., Conclusions: Reviewed case studies suggest that the use of SCs have unpredictable negative psychological and physiological effects. Predominant manifestations reported were anxiety, agitation, paranoia, hallucinations, tachycardia, nausea and vomiting, and diaphoresis., Practice Implications: Nurses provide the most direct and supportive care to patients who present for medical treatment after the use of SCs. Knowledge of clinical manifestations can facilitate supportive management of patients suspected of SCs use., (© 2013, Wiley Periodicals, Inc.)

Objective: To report a case of paranoid psychosis and cognitive impairment associated with Hepatitis C virus (HCV) antiviral therapy., Methods: Case report., Results: A 55-year-old male presented with paranoid psychosis and cognitive impairment, 4 months after initiating interferon-based HCV antiviral therapy. His psychosis resolved with discontinuation of therapy and initiation of risperidone, but his cognitive impairment persisted. His psychosis also re-emerged months later when attempting to titrate down his risperidone. Brain MRI demonstrated bilateral asymmetric subcortical and deep white matter changes, which were non-specific but may have rendered him susceptible to neuropsychiatric sequelae of antiviral therapy., Conclusion: This case emphasizes the importance of neuropsychiatric screening and monitoring of patients being treated with interferon-based therapy for HCV, particularly if there is evidence of previous neurologic disease., (© 2014.)

This was a naturalistic study of 23 abstinent cocaine-dependent patients and 38 controls who were studied using a paired-stimulus paradigm to elicit three mid-latency auditory evoked responses (MLAERs), namely, the P50, N100, and P200. Sensory gating was defined as the ratio of the S2 amplitude to the S1 amplitude. Psychosis-proneness was assessed using four Chapman psychosis proneness scales measuring perceptual aberration, magical ideation, social anhedonia, and physical anhedonia. Omnibus correlations based upon the entire sample revealed significant and differential relationships between the MLAER components and psychosis-proneness. Social Anhedonia scale scores accounted for the largest proportion of variance in the P50 gating ratio, while Perceptual Aberration scores accounted for the largest proportion of variance in P200 gating. Psychosis proneness and sensory gating appear to be associated. In particular, poorer P50 gating is related to higher scores on the Social Anhedonia scale in healthy controls and across mixed samples of cocainede-pendent patients and controls. These findings hold significance for the further understanding of the relationship between deficient sensory gating ability and the propensity to developing psychotic symptoms in a vulnerable population like cocaine-dependent individuals., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: This study aimed to review the available evidence-based literature on novel psychoactive substances and to inform health care professionals., Methods: Internet searches were carried out using Google and Yahoo by using specific key words. For each set of key words, the first 100 websites identified by Google and Yahoo were fully assessed, together with a further 5% of random samples selected by research randomizer of the remaining websites. Thus, a list of unique web forums was identified, and qualitative information was extracted. Available evidence-based literature were reviewed along with a user's experimentation with mephedrone, NRG-1, NRG-2 and Benzofury., Results: It showed that when a substance (mephedrone) became controlled, the vendors aggressively promote the sale of other new compounds (NRG-1, NRG-2, Benzofury) to attract vulnerable adults. The characteristics, toxicity and suggested management of these new compounds (NRG-1, NRG-2, Benzofury) are discussed., Conclusions: The arrival of hundreds of novel psychoactive substances for sale online has raised a number of public health and legal issues. Although evidence-based literature remains limited, few studies identified that most products do not contain the ingredients as advertised. Better levels of international cooperation and rapid share of available information may be needed to tackle this emerging problem., (Copyright © 2013 John Wiley & Sons, Ltd.)

We report the case of a 43 year old male with no prior psychiatric history with apparent tacrolimus-induced psychosis. Previous reports have identified other neurotoxic adverse effects due to tacrolimus, however, to our knowledge, there are few reports that describe psychosis induced by the immunosuppressant drug. Although psychosis may be a rare adverse effect, it can have significant impact on the long-term prognosis and treatment in transplant recipients. It is imperative to quickly identify patients who develop a mental status change while on tacrolimus and to work with the appropriate transplant team in managing these patients. Treatment usually calls for prompt discontinuation of tacrolimus, substituting with another immunosuppressant, and possible use of antipsychotics., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.

Background: Personality correlates highly with both cocaine and nicotine dependencies (CD, ND), and their co-morbid psychopathologies. However, little is known about the nature of these relationships. This study examined if environment (marriage) or genetics (a single SNP, CHRNA5*rs16969968) would moderate the correlation of personality with CD, ND and cocaine-induced paranoia (CIP) in African and European Americans (AAs, EAs)., Methods: 1432 EAs and 1513 AAs were examined using logistic regression. Personality was assessed by NEO-PI-R, while CD, ND and CIP were diagnosed according to DSM-IV. ND and CD were examined as binary traits and for the analysis of CIP, subjects were divided into 3 groups: (A) Controls with no CIP; (B) CD cases without CIP; and (C) CD cases with CIP. Multiple testing was Bonferroni-corrected., Results: For CD and ND in the EA population, marital status proved to be a significant moderator in their relationship with openness only (OR = 1.90, 95%CI = 1.36-2.64, p = 1.54e-04 and OR = 2.12, 95%CI = 1.52-2.90, p = 4.65e-06 respectively). For CIP, marriage was observed to moderate its correlation with openness and neuroticism (OR = 1.39, 95%CI = 1.18-1.63, p = 7.64e-04 and OR = 1.26, 95%CI = 1.12-1.42, p = 1.27e-03 respectively). The correlations moderated by rs16969968 were those of conscientiousness and CD (OR = 1.62, 95%CI: 1.23-2.12, p = 8.94e-04) as well as CIP (OR = 1.21, 95%CI: 1.11-1.32, p = 4.93e-04 when comparing group A versus group C). No significant interactions were observed in AA population. The Bonferroni-corrected significance threshold was set to be 1.67e-03., Conclusion: The role of personality in CD and CIP may be interceded by both environment and genetics, while in ND by environment only.

Abuse of the psychoactive "designer drug" methylenedioxypyrovalerone (MDPV) has become a serious international public health concern because of the severity of its physical and behavioral toxicities. MDPV is the primary ingredient in so-called "bath salts," labeled as such to avoid criminal prosecution and has only been classified recently as a controlled substance in the United States and some other countries. However, it remains a danger because of illegal sources, including the Internet. MDPV is a synthetic, cathinone-derivative, central nervous system stimulant and is taken to produce a cocaine- or methamphetamine-like high. Administered via oral ingestion, nasal insufflation, smoking, intravenous or intramuscular methods, or the rectum, the intoxication lasts 6 to 8 hours and has high addictive potential. Overdoses are characterized by profound toxicities, causing increased attention by emergency department and law enforcement personnel. Physical manifestations range from tachycardia, hypertension, arrhythmias, hyperthermia, sweating, rhabdomyolysis, and seizures to those as severe as stroke, cerebral edema, cardiorespiratory collapse, myocardial infarction, and death. Behavioral effects include panic attacks, anxiety, agitation, severe paranoia, hallucinations, psychosis, suicidal ideation, self-mutilation, and behavior that is aggressive, violent, and self-destructive. Treatment is principally supportive and focuses on counteracting the sympathetic overstimulation, including sedation with intravenous benzodiazepines, seizure-prevention measures, intravenous fluids, close (eg, intensive care unit) monitoring, and restraints to prevent harm to self or others. Clinical presentation is often complicated by coingestion of other psychoactive substances that may alter the treatment approach. Clinicians need to be especially vigilant in that MDPV is not detected by routine drug screens and overdoses can be life-threatening., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Rationale: Delta-9-tetrahydrocannabinol (THC) is one of the few cannabinoid receptor ligands that can be used to probe the cannabinoid system in humans. Despite increasing interest in the cannabinoid receptor system, use of intravenous THC as a research tool has been limited by concerns about its abuse liability and psychoactive effects., Objectives: This study aims to evaluate the safety of all intravenous THC studies conducted at this center for the past 13 years., Methods: Included were 11 studies with 266 subjects (14 schizophrenia patients and 252 healthy subjects, of whom 76 were frequent cannabis users), 351 active THC infusions, and 226 placebo infusions. Subjects were monitored for subjective and physical adverse events and followed up to 12 months beyond study participation., Results: There was one serious and 70 minor adverse events in 9.7% of subjects and 7.4% of infusions, with 8.5% occurring after the end of the test day. Nausea and dizziness were the most frequent side effects. Adverse events were more likely to be associated with faster infusion rates (2-5 min) and higher doses (>2.1 mg/70 kg). Of 149 subjects on whom long-term follow-up data were gathered, 94% reported either no change or a reduction in their desire to use cannabis in the post-study period, 18% stated that their cannabis use decreased, and 3% stated that it increased in the post-study period., Conclusions: With careful subject selection and screening, risk to subjects is relatively low. Safeguards are generally sufficient and effective, reducing both the duration and severity of adverse events.

Psychoactive bath salts are a relatively new group of designer drugs sold as tablets, capsules, or powder and pur-chased in places such as tobacco and convenience stores, gas stations, head shops, and the Internet. Bath salts are stimulant agents that mimic cocaine,lysergic acid diethylamide, methamphetamine, or methylenedioxymethamphetamine (ecstasy). The most common bath salts are the cathinone derivatives 3,4-methylenedioxypyrovalerone(MDPV), 4-methylmethcathinone(mephedrone), and 3,4-methylenedioxy-N-methylcathinone (methylone). The drugs cause intense stimulation, eu-phoria, elevated mood, and a pleasurable "rush" Tachycardia, hypertension,peripheral constriction, chest pain, hallucinations, paranoia, erratic behavior,inattention, lack of memory of substance use, and psychosis have been observed in those who have used bath salts. The U.S. Drug Enforcement Administration recently exercised an emergency authority to name three key ingredients in bath salts as Schedule I, thereby making them illegal to possess or sell in the United States. Nursing implications related to both clinical and educational settings are discussed.

Background: There has been an increase in the popularity of designer drugs known as "Bath Salts" in the United States. These products commonly contain mephedrone, mephylone, methylenedioxypyrovalerone (MDPV), or other cathinone derivatives with psychoactive properties similar to amphetamine and cocaine. Although recently outlawed, abuse of these products continues to occur in Mississippi., Methods: We report a 19-year-old male who presented with paranoia and auditory as well as visual hallucinations. Auditory effects included voices that prompted him to kill people. The patient displayed anxiety, paranoia, and exhibited repeated bouts of inappropriate laughter. Urine toxicology analysis via GC/ MS detected MDPV, a compound structurally similar to methylenedioxymethamphetamine (MDMA)., Conclusions: Clinicians should be aware that these designer drugs are not detected with common immunoassay drug screens. Symptoms most commonly associated with these substances include tachycardia, delusions, hallucinations, and paranoia. Psychosis, self harm, and death have been associated with some cases.

Of growing concern has been the phenomenon of psychoactive chemicals legally marketed as a variety of products such as "bath salts" or "herbal incense." There is little in the formal literature about actual adverse effects of such chemicals. We have two cases of a paranoid psychosis in individuals consuming methylenedioxypyrovalerone. A discussion of this chemical and its abuse follows., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Catechol-O-methyltransferase (genetic locus, COMT) is a major enzyme involved in catecholamine metabolism and has been associated with numerous psychiatric phenotypes. We studied COMT SNPs and haplotypes in cocaine-induced paranoia (CIP) in African-American (AA) and European-American (EA) populations. We genotyped 17 SNPs across the COMT locus in 319 AA pedigrees (848 individuals) and 302 EA pedigrees (707 individuals). Family-controlled association analyses were conducted using FBAT. We found SNP rs737865 to be nominally significantly associated in the AA family population (P = 0.05). In EAs, the best-known marker, rs4680 (Val158Met), was nominally significant in additive models (P = 0.03). SNP rs174696 also showed nominal significance in additive models (P = 0.02). We considered the three SNPs (rs737866-rs4680-rs174696) together in haplotype analysis in both family populations, using HBAT. The A-A-T haplotype was significantly associated with CIP in EAs (Z = 2.845; P = 0.0044, global P = 0.020). We then studied COMT SNPs in an additional 738 AA and 404 EA unrelated cocaine dependent individuals with and without paranoia. The A-A-T haplotype was significantly associated to CIP in the AA unrelated population (P = 0.0015). Two haplotypes, A-G-C and A-A-C, were significant in the EA unrelated population (P = 0.001 and 0.0003). We also identified rs4680 and three other SNPs, rs933271, rs5993883, and rs740603, as potentially functional variants, as predicted by a signature of positive selection in unrelated EAs and AAs. Based on our robust family-controlled and unrelated-affected analyses, we conclude that COMT is associated with CIP, possibly as a result of its role in the metabolism of dopamine and norepinephrine., (Copyright © 2011 Wiley-Liss, Inc.)

Marijuana (cannabis) is the most commonly abused drug by adolescents and young adults and also by people with schizophrenia or other psychotic disorders. An increasing number of studies suggest that regular cannabis users can show psychotic episodes similar to schizophrenic disorders but it still unclear if cannabis induced psychotic disorder is a distinct entity requiring special therapy or regular cannabis use consequently leads to schizophrenia. Therefore, we retrospectively compared psychotic patients with and without cannabis use by clinical profile. Clinical data of 85 patients with schizophrenia spectrum disorder were analyzed retrospectively. Cannabis use was not reported by 43 persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least 1 year (Cnbs1 subgroup). Clinical data were collected from electronic medical documentation of patients concerning anamnesis, family history, socio-demographic condition, symptoms and psychiatric state, acute and long-term therapies. Men were over-represented in the cannabis abuser group while mean age was lower among them compared to the Cnbs0 subgroup. Prevalence of suicidal attempts was increased in men without cannabis use. Patients without cannabis use spent more time in hospital and smoking was more frequent among them. Positive and negative symptoms and family history did not differ significantly between the two subgroups. Dosage, intensity and length of pharmacotherapy was different between the two subgroups. These results revealed that certain clinical aspects were different in case of cannabis-related schizophrenia spectrum disorder compared to schizophrenia.

Background: Prader Willi syndrome (PWS) without strict environmental modifications can lead to obesity associated with significant morbidity and mortality. In addition to increased appetite, these individuals have decreased energy expenditure with lower insulin like growth factor 1 (IGF1), which contributes to adiposity. No effective treatment is available for this condition. Endocannabinoid receptor CB1 antagonist, rimonobant, has been effective for treatment of obesity in adult subjects. Rimonabant promotes weight loss by multiple proposed mechanisms, including decreased appetite and lipogenesis, and increased energy expenditure. Therefore, we conducted this pilot study to evaluate the effect of rimonabant on body weight and composition of adults with PWS., Method: This was a double blind placebo controlled study. Body weight, total fat mass, fasting ghrelin, leptin, IGF1 and insulin like growth factor binding protein (IGFBP-3) were collected at baseline, and after 90 and 180 days of treatment with placebo or 20 mg of rimonabant., Results: Due to psychiatric adverse effects, 50% of subjects in the rimonabant group withdrew, and the study was terminated early (N=10) for safety concerns. There was a trend for weight loss, lower fat mass and higher IGF1 level at the end of study in this group. Leptin followed the fat mass and decreased with rimonabant treatment., Conclusion: Rimonabant administration may be efficacious for weight loss in adults with PWS; unfortunately it is associated with an unacceptably high risk of psychiatric side effects. Future CB1 antagonists will need a better psychiatric profile before considered in the treatment of obesity in this genetic condition., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Cocaine remains the second most used illicit drug in Europe, after cannabis, though levels of use vary between countries. This psychostimulant has become a noticeable part of the European drug scene. Cocaine dependence, a chronic, relapsing and multifactorial disorder, is a significant worldwide public health problem with somatic, legal, social, cognitive and psychological complications. The relationship between clinical psychotic symptoms and use of specific substances other than cannabis has received minimal attention in the literature. Psychotic symptoms and experience of paranoia and suspiciousness are reported during the use and the withdrawal of cocaine. Furthermore, although psychotic symptoms were found to be common among substance users, the risk for development of chronic psychotic disorder was found. In the light of recent epidemiological data stating that there is an increased cocaine use, that there is an increased number of patients entering drug treatment for primary cocaine use in Europe for several years and that cocaine users are an heterogeneous group, we made a review on the specific topic of cocaine-induced psychotic disorders. This review is based on Medline, EMBASE, PsycINFO and Google Scholar searches of English and French-language articles published between 1969 and February, 2010.

Interferon-ß is used in patients with multiple sclerosis to reduce autoimmunity; although other psychiatric side-effects are common, in contrast to interferon-alpha, psychosis has been reported only once. A patient with multiple sclerosis developed auditory hallucinations, paranoid delusions, and increased aggressiveness after 16 months of treatment with interferon-ß-1b, 250 mg every other day. He responded after about one month to antipsychotic treatment, but tended to relapse upon dose reduction, and after 2 years still needs antipsychotics to control his symptoms. Because there was no change in his magnetic resonance imaging between pre- and post-treatment with interferon, we concluded that psychosis was more related to interferon treatment than to the underlying disease.

Unlabelled: Cannabis can produce and/or exacerbate psychotic symptoms in vulnerable individuals. Early exposure to cannabis, particularly in combination with genetic factors, increases the risk of a subsequent, primary, psychotic disorder. Because paranoia is a common feature of stimulant abuse and cocaine-dependent individuals frequently endorse a history of cannabis abuse, we examined whether early cannabis exposure, in conjunction with polymorphic variation in the catechol-O-methyl transferase gene (COMT Val158Met), influences the risk for cocaine-induced paranoia (CIP)., Methods: Cannabis-use history was obtained in 1140 cocaine-dependent individuals from a family-based (affected sibling pair) study using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). Logistic regression and generalized estimating equations' analyses were used to examine the role of adolescent-onset cannabis use (< or =15 years of age) on CIP risk, both controlling for previously implicated CIP risk factors and familial relationships, and considering potential interactions with COMT Val158Met genotype., Results: Cocaine-dependent individuals who endorsed CIP had significantly higher rates of adolescent-onset cannabis use than those without CIP (62.2% vs. 50.2%; chi(2)=15.2, df=1, p<0.0001), a finding that remained after controlling for sibling correlations and other risk factors. There were no effects of COMT genotype or genotype by early cannabis onset interactions. A modest (OR=1.4) and nearly significant (p=0.053) effect of CIP status in probands on CIP status in siblings was also noted., Conclusions: Adolescent-onset cannabis use increases the risk of CIP in cocaine-dependent individuals. COMT genotype and its interaction with early cannabis exposure did not emerge as significant predictors of CIP. In addition, trait vulnerability to CIP may also be familial in nature., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, we created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA-induced paranoia. We administered the MEQ to 274 MA-dependent subjects. Of the total subjects, 45% (123) first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA-induced paranoia, respectively). Test-retest and inter-rater reliability for MA-induced paranoia showed substantial agreement (kappa = .77, p < .05 and kappa = .80, p < .05, respectively). First episodes of paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the Brief Symptom Inventory (BSI) paranoid ideation scale (rho = .27, p < .05). As expected, there was a poor correlation between paranoia on the MEQ and the BSI depression scale (rho = .14, p = .07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use. (Am J Addict 2010;00:1-14).

Opsoclonus-myoclonus syndrome (OMS) typically presents with chaotic eye movements and myoclonus with some patients exhibiting ataxia and behavioural disturbance. The pathogenesis may be inflammatory with an infectious or paraneoplastic trigger. In this report, we describe four HIV-infected cases with OMS presenting to a tertiary referral centre in Cape Town, South Africa, over a 10-year period. OMS was the initial neurological presentation of HIV-infection in three subjects of whom two had preserved CD4+ cell counts. Immunosuppressive therapy, mainly prednisone, led to a dramatic improvement of symptoms in all cases suggesting an inflammatory aetiology, consistent with the observation that HIV-infection can be associated with both inflammatory and autoimmune conditions. Three previous reports of OMS associated with HIV-infection have been documented including a sero-conversion syndrome and as part of an immune reconstitution syndrome. We suggest that in HIV-associated OMS the pathophysiology may be the consequence of a dysregulated immune system in which a reduced CD4/CD8 ratio, in addition to a critical level of functional CD4+ cells for efficient CD8+ cytotoxicity, results in dysfunction of the brainstem-cerebellar circuitry in susceptible individuals.

We recently reported that, in a European-American (EA) sample, the interaction between two cannabinoid receptor 1 gene (CNR1) variants significantly increased risk for drug dependence (DD), including cocaine dependence (CD). This study aimed to investigate directly the association between CNR1 and CD in four independent samples. Eight markers across the 45 kb CNR1 region and four large samples, ie, family-based European-American (EA) sample (n=734), case-control EA sample (n=862), family-based African-American (AA) sample (n=834) and case-control AA sample (n=619) were examined in the present study. We investigated the association of these markers with CD and cocaine-induced paranoia (CIP) in the EA family sample first, and then replicated positive results in the other three samples. The interaction between two independent CNR1 variants, ie, the G allele-containing genotypes of rs6454674 (SNP3(G+)), and the T/T genotype of rs806368 (SNP8(T)/T), significantly increased risk for CD in the EA family (P(GEE)=0.015) and EA case-control (P(regression)=0.003) samples. EA subjects with SNP3(G+) and SNP8(T)/T had higher risk to develop CD than those EA subjects with the other genotypes for these two SNPs (LR+ =1.4). The SNP3(G)-SNP8(T)haplotype also showed significant association (P=0.018) with CD in the EA case-control sample. SNP8-containing haplotypes showed significant association with both CD (P(global)=0.007) and CIP (P(global)=0.003) in the EA family sample. In the AA family sample, SNP8(T)/T significantly conferred higher risk for CD (P=0.019). We conclude that two independent CNR1 variants have significant interaction effects on risk for CD in EAs; they may also have effects on risk for CD in AAs.

A 24-year-old Caucasian female was voluntarily admitted to an inpatient psyciatric unit after starting varenicline (Chantix). She reported feelings of paranoia, anxiety and suicidal ideation. She had no known history of psychiatric illness and was on no other medications prior to starting varenicline. This was her first attempt at smoking cessation, and she decided to use varenicline at the recommendation of her primary care provider and the South Dakota QuitLine program. We report this case to inform health care providers that the potential for psychiatric effects is possible, even in those individuals who do not have a history of psychiatric illnesses.

As a competitive adenosine antagonist, caffeine affects dopamine transmission and has been reported to worsen psychosis in people with schizophrenia and to cause psychosis in otherwise healthy people. We report of case of apparent chronic caffeine-induced psychosis characterized by delusions and paranoia in a 47-year-old man with high caffeine intake. The psychosis resolved within 7 weeks after lowering caffeine intake without use of antipsychotic medication. Clinicians might consider the possibility of caffeinism when evaluating chronic psychosis.

Cannabis use has increased greatly over the last three decades. The various types of cannabis differ in their concentration of the main psychoactive component, Delta-9-tetrahydrocannabinol (THC), and the other major ingredient, cannabidiol (CBD). Plant engineering has maximized levels of THC, thus increasing the potency of street cannabis. It is well known that cannabis intoxication can cause brief psychotic symptoms like paranoia, whilst recent evidence demonstrates that heavy use of cannabis increases the risk of chronic psychoses like schizophrenia; genetic vulnerability seems to predispose some people to a higher risk. This paper starts to consider the neurochemical mechanisms whereby cannabis use increases the risk of psychosis.

Background: This study reports a new measure of psychotomimetic states in the context of cannabis and ketamine use. The Psychotomimetic States Inventory (PSI) has sub-scales of Delusory Thinking, Perceptual Distortions, Cognitive Disorganization, Anhedonia, Mania and Paranoia., Methods: The PSI was administered in two independent group, repeated measures designs: an experimental study of ketamine and a naturalistic study of cannabis., Results: Both cannabis and ketamine produced reliable increases in ratings of psychotomimetic state effects across several sub-scales., Conclusions: The PSI is a potentially useful measure of the nature and extent of the phenomenological effects of psychotropic drugs in schizophrenia-related research.