[The use of "virado" as a harm reduction strategy among crack users in the State of Pernambuco, Brazil]. / El uso de "virado" como estrategia de reducción de daños entre los usuarios de crack del estado de Pernambuco, Brasil.

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.

El objetivo del estudio es discutir uno de los usos del crack denominado "virado", como estrategia de reducción de daños entre las personas que usan crack en Pernambuco, Brasil. Se realizó una investigación cualitativa y transversal. Desde marzo hasta agosto de 2016, se realizaron entrevistas semiestructuradas sobre la cultura del uso de crack a 39 personas que usan esta substancia. El límite de participantes se estableció por el criterio de saturación. Los datos se analizaron con la técnica de análisis de contenido. Las personas que participaron relataron que el virado es una manera distinta de utilizar el crack y, al comparar su efecto con el uso fumado o inhalado, mencionaron que el virado produce menos impacto en las relaciones interpersonales y en la libido, además de reducir el uso compulsivo de crack, cuestiones que se podrían considerar como estrategias de reducción de daños. Un aspecto negativo es que comparten los canutos para aspirar el virado, lo cual es una situación de riesgo para la transmisión de enfermedades infecciosas. Conocer la cultura del uso del crack en distintas formas y situaciones es imprescindible para la planificación y desarrollo de acciones de atención a la salud.

Brivaracetam: First Canadian Experience in an Intractable Epilepsy Population.

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.

El uso de "virado" como estrategia de reducción de daños entre los usuarios de crack del estado de Pernambuco, Brasil / The use of "virado" as a harm reduction strategy among crack users in the State of Pernambuco, Brazil

RESUMEN El objetivo del estudio es discutir uno de los usos del crack denominado "virado", como estrategia de reducción de daños entre las personas que usan crack en Pernambuco, Brasil. Se realizó una investigación cualitativa y transversal. Desde marzo hasta agosto de 2016, se realizaron entrevistas semiestructuradas sobre la cultura del uso de crack a 39 personas que usan esta substancia. El límite de participantes se estableció por el criterio de saturación. Los datos se analizaron con la técnica de análisis de contenido. Las personas que participaron relataron que el virado es una manera distinta de utilizar el crack y, al comparar su efecto con el uso fumado o inhalado, mencionaron que el virado produce menos impacto en las relaciones interpersonales y en la libido, además de reducir el uso compulsivo de crack, cuestiones que se podrían considerar como estrategias de reducción de daños. Un aspecto negativo es que comparten los canutos para aspirar el virado, lo cual es una situación de riesgo para la transmisión de enfermedades infecciosas. Conocer la cultura del uso del crack en distintas formas y situaciones es imprescindible para la planificación y desarrollo de acciones de atención a la salud.

ABSTRACT 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.

Can typical and atypical antipsychotics show differential effectiveness in treating paranoia and hallucinations in schizophrenia?

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.

Paranoid schizophrenia and methamphetamine-induced paranoia are both characterized by a similar LINE-1 partial methylation profile, which is more pronounced in paranoid schizophrenia.

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.

Synthetic cannabinoid use among college students.

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.

Methamphetamine (MA) Use Induces Specific Changes in LINE-1 Partial Methylation Patterns, Which Are Associated with MA-Induced Paranoia: a Multivariate and Neuronal Network Study.

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.

Impulse control disorders in patients with prolactinoma receiving dopamine agonist therapy: a prospective study with 1 year follow-up.

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.

Methamphetamine psychosis: insights from the past.

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.

[Acute Psychosis after Consumption of Synthetic Cannabinoids]. / Akute Psychose nach Konsum von synthetischen Cannabinoiden.

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.

The impact of amphetamine-type stimulants on emergency services.

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.

How cannabis causes paranoia: using the intravenous administration of ∆9-tetrahydrocannabinol (THC) to identify key cognitive mechanisms leading to paranoia.

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.

Clinical features of methamphetamine-induced paranoia and preliminary genetic association with DBH-1021C→T in a Thai treatment cohort.

AIMS: To explore the clinical features of methamphetamine-induced paranoia (MIP) and associations between MIP and a genetic polymorphism in dopamine ß-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 ß-hydroxylase is associated with methamphetamine-induced paranoia and influences smoking initiation.

Paranoid psychosis and cognitive impairment associated with hepatitis C antiviral therapy.

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.

Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene.

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.

A review of clinical manifestations in adolescent and young adults after use of synthetic cannabinoids.

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.