Cannabinoids impact on pregnancy: effects in trophoblast cells

Cannabinoids (CBs) can be classified as: phytocannabinoids, the constituents of the Cannabis sativa plant; synthetic cannabinoids lab-synthesized and the endocannabinoids that are endogenous lipid mediators. Cannabinoid compounds activate cannabinoid receptors – CB1 and CB2. The most prevalent psychoactive phytocannabinoid is Δ9tetrahydrocannabinol (THC), but more than 60 different CBs were already identified in the plant. The best characterized endocannabinoids (eCBs) are anandamide (AEA) and 2arachidonoylglycerol (2-AG), that are involved in several physiological processes including synaptic plasticity, pain modulation, energy homeostasis and reproduction. On the other hand, some synthetic cannabinoids that were initially designed for medical research, are now used as drugs of abuse. During the period of placental development, highly dynamic processes of remodeling occur, involving proliferation, apoptosis, differentiation and invasion of trophoblasts. It is known that a tight control of eCBs levels is required for normal pregnancy progression and that eCBs are involved in trophoblast cells turnover. Therefore, by sharing activation of the same receptors, exposure to exocannabinoids either by recreational or medicinal use may lead to alterations in the eCBs levels and in the endocannabinoid system homeostasis In this work, it was studied the impact of CBs in BeWo trophoblastic cells and in primary cultures of human cytotrophoblasts. Cells were treated for 24 hours with different concentrations of THC, the synthetic cannabinoid WIN‐55,212 (WIN) and 2-AG. Treatment with THC did not affect BeWo cells viability while WIN and 2-AG caused a dose-dependent viability loss. Morphological studies together with biochemical markers indicate that 2-AG is able to induce apoptosis in cytotrophoblasts. On the other hand, morphological studies after acridine orange staining suggest that autophagy may take part in WIN-induced loss of cell viability. All cannabinoids caused a decrease in mitochondrial membrane potential (Δψm) but only 2-AG led to ROS/RNS generation, though no changes in glutathione levels were observed. In addition, ER-stress may be involved in the 2-AG induced-oxidative stress, as preliminary results point to an increase in CCAAT-enhancer-binding protein homologous protein (CHOP) expression. Besides the decrease in cell viability, alterations in cell cycle progression were observed. WIN treatment induced a cell cycle arrest in G0/G1 phase, whereas 2-AG induced a cell cycle arrest in G2/M phase. Here it is reinforced the relevance of cannabinoid signaling in fundamental processes of cell proliferation and cell death in trophoblast cells. Since cannabis-based drugs are the most consumed illicit drugs worldwide and some of the most consumed recreational drugs by pregnant women, this study may contribute to the understanding of the impact of such substances in human reproduction.

Perfil de ácidos gordos de sementes: benefícios para a saúde

Introdução e Objetivos: Nos últimos anos tem-se verificado um aumento na procura de sementes oleaginosas, sobretudo de girassol, sésamo, linhaça e pevides de abóbora, porque o seu consumo está associado a efeitos benéficos para a saúde. Recentemente, surgiram no mercado "novas" sementes que agora fazem parte da nossa alimentação, como por exemplo, as sementes de chia e de papoila. Normalmente, este tipo de produtos são adicionados a outros alimentos como batidos, iogurtes, sumos de fruta, ou são usados como ingredientes na produção de produtos de padaria e/ou pastelaria. O objetivo deste trabalho foi determinar o perfil de ácidos gordos de diferentes tipos de sementes que estão frequentemente disponíveis no mercado Português. Material e Métodos: Foram adquiridas em 2015, nas superfícies comerciais e ervanárias da região de Lisboa, oito tipos de sementes. Determinou-se o perfil de ácidos gordos por cromatografia gasosa das seguintes amostras: Papoila (Papaver somniferum L.), chia (Salvia hispanica), alpista (Phalaris canariensis L.), cânhamo (Cannabis sativa L.), abóbora (Cucurbita L.), girassol (Helianthus annuus L.), sésamo (Sesamum indicum L.) e linhaça (Linum usitatissimum L.). Resultados e Discussão: Verificou-se que para as sementes de linhaça e chia o principal ácido gordo foi o ácido alfa-linolénico (C18:3, n3), com valores que variaram entre 45,9% e 64,4% do total de ácidos gordos, para sementes de linhaça e sementes de chia, respetivamente. Para as restantes amostras o principal ácido gordo foi o ácido linoleico (C18:2, n6). As sementes de papoila apresentaram o maior teor de ácido linoleico (71,6% do total de ácidos gordos), e as sementes de sésamo apresentaram o teor mais elevado de ácido oleico (39,6% do total de ácidos gordos). Conclusões: Todas as sementes analisadas apresentam um perfil de ácidos gordos saudável, sendo estes sobretudo ácidos gordos insaturados relacionados com efeitos benéficos na prevenção de doenças cardiovasculares. Este estudo fornece novos dados sobre o perfil de ácidos gordos de sementes oleaginosas amplamente disponíveis, que poderão ser úteis para avaliar o padrão alimentar da população Portuguesa, mas também para o desenvolvimento de futuras recomendações e orientações alimentares.

Evidencia sobre la eficacia de cannabinoides en el dolor neuropático oncológico

Contexto: La eficacia de los cannabinoides en el dolor neuropático es desconocida. El control del dolor es determinante en los pacientes ya que genera un impacto negativo en la calidad de vida de los pacientes. Objetivo: El presente trabajo pretende demostrar la evidencia sobre la eficacia de los medicamentos cannabinoides en el control del dolor neuropático oncológico, mediante la evaluación de la literatura disponible. Metodología: Se realizó una revisión sistemática de literatura incluyendo estudios experimentales, observacionales y revisiones sistemáticas en un periodo de 15 años. Se incluyeron todos los estudios desde el años 2000 con evidencia IB según la escala de evidencia de Oxford. Resultados: Cuatro estudios cumplieron criterios para su inclusión, sin embargo la evidencia es baja y no permite recomendar o descartar los cannabinoides como terapia coadyuvante en control del dolor neuropático oncológico. La combinación de THC/CDB (Sativex®) parece ser un medicamento seguro pues no se reportaron muertes asociadas a su uso, sin embargo la presentación de eventos adversos a nivel gastrointestinal y neurológico podría aumentar el riesgo de interacciones medicamentosas y tener un impacto negativo en la calidad de vida de los pacientes oncológicos. Conclusiones: No hay suficiente literatura y la evidencia no es suficiente para recomendar o descartar el uso de los cannabinoides en dolor neuropático oncológico. Futuros estudios deben realizarse para analizar el beneficio de estos medicamentos. Aunque ética y socialmente hay resistencia para el uso de los cannabinoides, actualmente hay una gran discusión política en el mundo y en Colombia para su aceptación como terapia en el control del dolor.

Predictors of cannabis use in men with and without psychosis

Background: Factors associated with cannabis use among people with psychosis are not well understood. ----- Aims: To examine whether people with psychosis and age-matched controls modified cannabis use in response to recent experiences. ----- Method: This study predicted 4 weeks of cannabis use prospectively, using expectancies derived from recent occasions of use. ----- Results: People with psychosis used cannabis less frequently than controls, but had more cannabis-related problems. More negative cannabis expectancies resulted in less frequent cannabis use over Follow-up. The psychosis group was more likely to moderate cannabis use after negative effects than controls. ----- Conclusions: Results offer optimism about abilities of people with psychosis tomoderate cannabis use in the short term.

Cannabis use and misuse prevalence among people with psychosis

Background: Increasing attention has been given by researchers to cannabis use in individuals with psychosis. As psychoses are relatively low-prevalence disorders, research has been mostly been restricted to small-scale studies of treatment samples.The reported prevalence estimates obtained from these studies vary widely. Aims: To provide prevalence estimates based on larger samples and to examine sources of variability in prevalence estimates across studies. Method: Data from 53 studies of treatment samples and 5 epidemiological studies were analysed. Results: Based on treatment sample data, prevalence estimates were calculated for current use (23.0%), current misuse (11.3%),12-month use (29.2%),12-month misuse (18.8%), lifetime use (42.1%) and lifetime misuse (22.5%). Epidemiological studies consistently reported higher cannabis use and misuse prevalence in people with psychosis. Conclusions: The factor most consistently associated with increased odds of cannabis prevalence was specificity of diagnosis. Factors such as consumption patterns and study design merit further consideration.

Reasons for cannabis use in men with and without psychosis

Psychoses are relatively low prevalence disorders that have a disproportionately negative impact on individuals and society. Cannabis use is one factor that can exacerbate the negative consequences associated with psychotic disorders. Relatively few studies have examined the effects or reasons for using cannabis self-reported by individuals with psychosis. The present study is the first known to compare directly such factors in individuals with and without psychosis, within a single study. At baseline and follow-up participants with psychosis most commonly reported using cannabis for positive mood alteration (36% and 42%), coping with negative affect (27% and 29%) and for social activity reasons (38% and 29%). The control group most commonly reported using cannabis for relaxation (34% and 43%) and social activity reasons (49% and 51%). Participants with psychosis were less likely to report relaxation as the most important effect after use (27%) or expect it at follow-up (49%) compared to the control group (53% and 70%). In both groups, addiction and positive affect enhancement were the composite variable scores correlated most consistently with concurrent amount and frequency of use.

The reliability and validity of the Severity of Dependence Scale for detecting cannabis dependence in psychosis.

Aims: To determine the reliability and validity of the Severity of Dependence Scale (SDS) for detecting cannabis dependence in a large sample of in-patients with a schizophrenia spectrum disorder. Design: Cross-sectional study. Participants: Participants were 153 in-patients with a schizophrenia spectrum disorder in Brisbane, Australia. Measurements: Participants were administered the SDS for cannabis dependence in the past 12 months. The presence of Diagnostic and Statistical Manual Version-IV (DSM-IV) cannabis dependence in the previous 12 months was assessed using the Comprehensive International Diagnostic Interview (CIDI). Findings: The SDS had high levels of internal consistency and strong construct and concurrent validity. Individuals with a score of ≥2 on the SDS were nearly 30 times more likely to have DSM-IV cannabis dependence. The SDS was the strongest predictor of DSM-IV cannabis dependence after controlling for other predictor variables. Conclusions: The SDS is a brief, valid and reliable screen for cannabis dependence among people with psychosis

Being stoned : a review of self-reported cannabis effects.

Although there has been considerable research into the adverse effects of cannabis, less attention has been directed toward subjective effects that may be associated with ongoing cannabis use. Examination of self-reported cannabis effects is an important issue in understanding the widespread use of cannabis. While reviews have identified euphoria as a primary factor in maintaining cannabis use, relaxation is the effect reported most commonly in naturalistic studies of cannabis users, irrespective of the method used. Self-reported effects in 12 naturalistic and 18 laboratory studies were compared. Regardless of methodology there was considerable variation in the effects experienced. Variation has been reported in terms of opposite effects being experienced by different individuals, variation of effects by individuals within a single occasion and between occasions of use. Factors that might explain this variation are outlined. Limitations of the available literature and suggested directions for future research are discussed.

Genetic Analysis of Tolerance to Rice Tungro Bacilliform Virus in Rice (Oryza sativa L.) Through Agroinoculation

Balimau Putih [an Indonesian cultivar tolerant to rice tungro bacilliform virus (RTBV)] was crossed with IR64 (RTBV, susceptible variety) to produce the three filial generations F1, F2 and F3. Agroinoculation was used to introduce RTBV into the test plants. RTBV tolerance was based on the RTBV level in plants by analysis of coat protein using enzyme-linked immunosorbent assay. The level of RTBV in cv. Balimau Putih was significantly lower than that of IR64 and the susceptible control, Taichung Native 1. Mean RTBV levels of the F1, F2 and F3 populations were comparable with one another and with the average of the parents. Results indicate that there was no dominance and an additive gene action may control the expression of tolerance to RTBV. Tolerance based on the level of RTBV coat protein was highly heritable (0.67) as estimated using the mean values of F3 lines, suggesting that selection for tolerance to RTBV can be performed in the early selfing generations using the technique employed in this study. The RTBV level had a negative correlation with plant height, but positive relationship with disease index value

Validation of the Cannabis Expectancy Questionnaire (CEQ) in adult cannabis users in treatment

Background Outcome expectancies are a key cognitive construct in the etiology, assessment and treatment of Substance Use Disorders. There is a research and clinical need for a cannabis expectancy measure validated in a clinical sample of cannabis users. Method The Cannabis Expectancy Questionnaire (CEQ) was subjected to exploratory (n = 501, mean age 27.45, 78% male) and confirmatory (n = 505, mean age 27.69, 78% male) factor analysis in two separate samples of cannabis users attending an outpatient cannabis treatment program. Weekly cannabis consumption was clinically assessed and patients completed the Severity of Dependence Scale-Cannabis (SDS-C) and the General Health Questionnaire (GHQ-28). Results Two factors representing Negative Cannabis Expectancies and Positive Cannabis Expectancies were identified. These provided a robust statistical and conceptual fit for the data. Internal reliabilities were high. Negative expectancies were associated with greater dependence severity (as measured by the SDS) and positive expectancies with higher consumption. The interaction of positive and negative expectancies was consistently significantly associated with self-reported functioning across all four GHQ-28 scales (Somatic Concerns, Anxiety, Social Dysfunction and Depression). Specifically, within the context of high positive cannabis expectancy, higher negative expectancy was predictive of more impaired functioning. By contrast, within the context of low positive cannabis expectancy, higher negative expectancy was predictive of better functioning. Conclusions The CEQ is the first cannabis expectancy measure to be validated in a sample of cannabis users in treatment. Negative and positive cannabis expectancy domains were uniquely associated with consumption, dependence severity and self-reported mental health functioning.

The Cannabis Expectancy Questionnaire for Men who have Sex with Men (CEQ-MSM): A measure of substance-related beliefs

Objective Substance-related expectancies are associated with substance use and post-substance use thoughts, feelings and behaviours. The expectancies held by specific cultural or sub-cultural groups have rarely been investigated. This research maps expectancies specific to gay and other men who have sex with men (MSM) and their relationship with substance patterns and behaviours following use, including sexual practices (e.g., unprotected anal intercourse). This study describes the development of a measure of such beliefs for cannabis, the Cannabis Expectancy Questionnaire for Men who have Sex with Men (CEQ-MSM). Method Items selected through a focus group and interviews were piloted on 180 self-identified gay or other MSM via an online questionnaire. Results Factor analysis revealed six distinct substance reinforcement domains (“Enhanced sexual experience”, “Sexual negotiation”, “Cognitive impairment”, “Social and emotional facilitation”, “Enhanced sexual desire”, and “Sexual inhibition”). The scale was associated with consumption patterns of cannabis, and in a crucial test of discriminant validity not with the consumption of alcohol or stimulants. Conclusions The CEQ-MSM represents a reliable and valid measure of outcome expectancies, related to cannabis among MSM. Future applications of the CEQ-MSM in health promotion, clinical settings and research may contribute to reducing harm associated with substance use among MSM, including HIV transmission.