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Cannabis is the world's most widely used illicit drug. It can impair verbal learning and induce psychosis, both acutely and possibly following long term use. But, where cannabis acts in the brain to impair verbal learning and induce psychotic symptoms is unclear. The aim of this study was to clarify how one of the main psychoactive ingredients of cannabis, delta-9-tetrahydrocannabinol (THC) acts on the brain to impair verbal learning and induce psychotic symptoms.
15 healthy males with minimal exposure to cannabis, were studied on 2 occasions approximately 1 month apart, following oral administration of 10mg of THC or placebo 1 hour prior to scanning, in a double-blind design. MR images were acquired on a 1.5T GE camera while subjects performed a Verbal paired associates task with separate encoding followed by retrieval conditions, with the conditions repeated in the same sequence 4 times. We examined the main effects of drug, task and drug- task interactions.
Administration of THC abolished the normal linear decrement in parahippocampal activation across successive encoding blocks and was associated with a trend for impaired word recall. Administration of THC also altered the normal time-dependent change in ventral striatal activation during retrieval of word pairs which was directly correlated with concurrently induced psychotic symptoms.
These results suggest that impairment in learning and verbal memory associated with cannabis use may be mediated through its action in the medial temporal cortex while psychotic symptoms may be induced through its action in the ventral striatum.
There is considerable interest in the therapeutic potential of Cannabidiol (CBD), the second most abundant component of Cannabis. While delta-9-THC, the main psychoactive ingredient of cannabis, impairs memory and induces anxiety and psychotic symptoms acutely and increases the risk of psychotic disorders in regular cannabis users, CBD does not impair memory, may have anxiolytic and possibly antipsychotic effects. Hence, we compared directly the acute neural effects of these two active ingredients of cannabis, by combining pharmacological challenge with fMRI. Using a double-blind, repeated measures design and oral challenge with 10mg of delta-9-THC, 600mg of CBD or placebo in 15 healthy volunteers, we examined whether delta-9-THC and CBD have opposing effects on the neural substrates of verbal memory and fear processing and whether they also have opposing effects on the neural substrates of anxiety and psychotic symptoms induced by delta-9-THC. Delta-9-THC induced anxiety and psychotic symptoms acutely while there was a trend for a reduction in anxiety but no change in psychotic symptoms with CBD. During the memory task, delta-9-THC attenuated and CBD increased activation in the striatum bilaterally. Effect of delta-9-THC on striatal activation was inversely correlated with the psychotic symptoms induced by it concomitantly. During the processing of fearful faces, delta-9-THC increased and CBD attenuated activation in the amygdala and these effects correlated with their anxiogenic and anxiolytic effects respectively. These opposing effects of CBD on the key neural substrates for psychotic symptoms and anxiety induced by delta-9-THC may suggest its possible therapeutic role in countering these conditions.
Cannabis has well established effects on cognitive processing but the neural basis of these is unclear. We used functional neuroimaging to investigate this, focusing on tasks that engaged verbal memory and response inhibition.
Subjects were 15 healthy males who had used cannabis < 25 times in their lifetime. Each subject was studied on 3 occasions, and was given either THC, CBD or placebo 1 hour prior to scanning, in a double-blind design. The order of drug administration was randomised and there was 1 month between each scanning session. During each session, images were acquired on a 1.5T GE camera while subjects performed a verbal paired associates memory task and a Go/No Go task. The modulatory effects of THC and CBD relative to placebo were examined by comparing activation during each task.
During the encoding phase of the memory task THC attenuated activation in the left temporal cortex compared to placebo. During the go-no go task, THC attenuated activation in the right inferior frontal cortex. Neither of these effects were attributable to differences in behavioural performance, sedation, or intoxication. The severity of psychotic symptoms provoked by THC was a function of its effect on right inferior frontal activation during response inhibition.
The effects of cannabis on verbal memory and motor control may be mediated through the influence of THC on left temporal and right inferior frontal activity, respectively. The induction of psychotic symptoms by cannabis may reflect an effect of THC on right inferior frontal activity.
The study sought to examine the neurophysiological effects of cannabidiol (CBD) on the emotional processing using functional Magnetic Resonance Imaging (fMRI).
Fifteen healthy male participants (age range 18-35) with a lifetime exposure to cannabis of 15 times or less were recruited in a double blind event-related fMRI design. Prior to each scanning session, participants were given an oral dose of either 600mg CBD or a placebo. The blood levels of drugs were monitored via an intravenous line, while systolic and diastolic blood pressure and heart rate (beats per minute) were recorded manually. During the scan, subjects were presented with 10 different facial identities, each identity expressing 50% or 100% intensities of fear or a neutral expression. Neuropsychological performance and symptoms ratings were recorded at baseline, immediately before scanning (1 hr), immediately after scanning (2 hr), and one hour post scanning (3 hr).
CBD had no significant effect on the gender discrimination task. Reaction times were significantly faster when processing 100% fearful faces than compared to 50% fearful and neutral faces. CBD had a significant effect on brain activation in response to faces with emotional expressions, decreasing activation in the right posterior cingulate gyrus and in the right cerebellum, when compared to placebo. Furthermore, a significant interaction effect was observed. In the right cingulate gyrus CBD attenuated activation during the processing of intense fearful faces but had no effect of neural response to neutral or mild fearful faces.
CBD significantly modulates the neurophysiological response associated with anxiety.
This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task.
Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design.
Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms.
These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.
Neuropsychological and neuroimaging studies of response inhibition in cannabis users have reported inconsistent results. The age of onset of cannabis use and individual genetic differences may play a critical role in the regulation of inhibition in cannabis users.
We examine the influence of COMT Val158Met functional polymorphism on the response inhibition brain network in a group of early-onset chronic cannabis users compared with healthy controls.
fMRI data was acquired from 27 chronic cannabis users who began use cannabis before 16 years of age, and 29 non-using control subjects matched in terms of age, educational level and intelligence quotient while undergoing the Multi-Source Interference Task (MSIT). Participants were male, Caucasians aged between 18 and 30 years. All were assessed by a structured psychiatric interview (PRISM) to exclude any lifetime Axis-I disorder (DSM-IV). COMT genotyping was performed and resonance imaging data was analysed by voxel-based morphometry (VBM).
Both groups did not differ on their behavioural performance and brain responses during the MSIT task. A significant group-by-genotype interaction was observed on task-related brain activation (and on MSIT reaction times), in which met carrier load was associated with increased activation in cannabis users and val carrier load with increased activation in controls. The interaction pattern included the medial frontal cortex, ACC, inferior frontal gyrus, ventral striatum, anterior mesencephalon, inferior parietal and superior temporal cortices and the PCC.
Chronic cannabis exposure interacts with the genetically driven dopamine function in the modulation of the neural mechanisms related to response inhibition.
Increased psychotomimetic response to cannabis is demonstrated in psychosis-prone individuals. Early use of cannabis has poorer prognostic outcomes. However, as yet no cut-off age for early use has been established.
Aims and objectives
To determine, if age at first use affects later cannabis experiences and to determine if a “critical age” of first use exists for psychotomimetic cannabis experiences.
The cannabis experiences questionnaire (CEQ) (EUGEI version) was administered to a large internet-based non-clinical sample. Regression analysis was conducted of age at first use against CEQ scores controlling for gender, age frequency of use and duration of use. To determine cut-off age: independent ‘t’ tests (parametric) and Mann–Whitney-U tests (non-parametric) were used to determine significance of differences in CEQ scores at cut-off ages from 12-25.
We obtained data for 1115 participants. Younger age at first use was significantly associated with increased psychotomimetic experiences (adjusted P < 0.001). All cannabis experiences were increased in in those commencing at younger age at every cut off age from 17 to 22 (P < 0.001) with maximal difference at 22. Psychotic experiences significantly varied from age of first use of 19 to 22 with maximal difference at cut-off ages 20, 21 and 22 (P < 0.001). Pleasurable experiences were significantly reduced in those commencing later at every cut-off age from age of use 17 to 22 (P < 0.001) with maximal difference between groups at age 20.
Later onset of use is associated with reduced cannabis experiences till the early 1920s. This may have public health implications.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Duck production has the potential to play a major role in agricultural economy. Asian countries alone contribute 84.2% of total duck meat produced in the world. Driven by the demand of processed foods among consumers, the global duck meat market is expected to grow at a steady pace, reaching a value of about $11.23 billion in the coming years. Duck meat has higher muscle fibre content in breast meat compared to chicken, and is considered as red meat. Moreover, due to a higher fat content (13.8%) than chicken and a stronger gamey flavour, duck meat can be less appreciated by the consumer. Development and diversification of ready-to-eat duck meat products is expected to increase consumption levels. Hence, the status of duck meat production, physicochemical properties, processing, including traditional products, and development of novel value-added ready-to-eat products from spent duck meat is discussed in detail to explore its importance as an alternative to chicken.
Evidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels.
We compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels.
Individuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma.
Our results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis.
The solar active region (AR) 12192 was one of the most flare productive region of solar cycle 24, which produced many X-class flares; the most energetic being an X3.1 flare on October 24, 2014 at 21:10 UT. Customarily, such events are believed to be triggered by magnetic reconnection in coronal magnetic fields. Here we use the vector magnetograms from solar photosphere, obtained from Heliospheric Magnetic Imager (HMI) to investigate the magnetic field topology prior to the X3.1 event, and ascertain the conditions that might have caused the flare. To infer the coronal magnetic field, a novel non-force-free field (NFFF) extrapolation technique of the photospheric field is used, which suitably mimics the Lorentz forces present in the photospheric plasma. We also highlight the presence of magnetic null points and quasi-separatrix layers (QSLs) in the magnetic field topology, which are preferred sites for magnetic reconnections and discuss the probable reconnection scenarios.
Magnetic reconnections (MRs) for various magnetic field line (MFL) topologies are believed to be the initiators of solar eruptive events like flares and coronal mass ejections (CMEs). Consequently, important is a thorough understanding and quantification of the MFL topology and their evolution which leads to MRs. Contemporary standard is to extrapolate the coronal MFLs using equilibrium models where the Lorentz force on the coronal plasma is zero everywhere. In tandem, a non-force-free-field (NFFF) extrapolation scheme has evolved and allows for a Lorentz force which is non-zero only at the photosphere but asymptotically vanishes with height. The paper reports magnetohydrodynamic (MHD)- simulations initiated by NFFF extrapolation of the coronal MFLs for a flare producing active region NOAA 11158. Interestingly, quasi-separatrix layers (QSLs) which facilitate MRs are detected in the extrapolated MFLs and, here the paper makes an attempt to asses the role of QSLs in the flare onsets.
This paper details on the discovery of 21 pulsars using the Giant Metrewave Radio Telescope (GMRT) from targeted (Fermi directed search) and blind surveys (GMRT High Resolution Southern Sky - GHRSS) and results from the follow up studies. We discovered seven millisecond pulsars (MSPs) in the Fermi directed searches, which are the first Galactic MSPs discovered with the GMRT. We have discovered 13 pulsars (including a MSP and two mildly recycled pulsars) with the GHRSS survey, which is an off-Galactic-plane survey at 322 MHz with complementary target sky (declination range −40 deg to −54 deg) to other ongoing low-frequency surveys by GBT and LOFAR. The simultaneous time-domain and imaging study for localising pulsars and transients and efficient candidate investigation with machine learning are some of the features of the GHRSS survey, which are also finding application in the SKA design methodology.
Substance use may increase the risk of non-adherence to antipsychotics, resulting in negative outcomes in patients with psychosis.
We aimed to quantitatively summarize evidence regarding the effect of cannabis use, the most commonly used illicit drug amongst those with psychosis, on adherence to antipsychotic medication. Studies were identified through a systematic database search. Adopting random-effects models, pooled odds ratios (OR) for risk of non-adherence to antipsychotic medications were calculated comparing: cannabis-users at baseline v. non-users at baseline; non users v. continued cannabis users at follow-up; non-users v. former users at follow-up; former users v. current users.
Fifteen observational studies (n = 3678) were included. Increased risk of non-adherence was observed for cannabis users compared to non-users (OR 2.46, n = 3055). At follow-up, increased risk of non-adherence was observed for current users compared to non-users (OR 5.79, n = 175) and former users (OR 5.5, n = 192), while there was no difference between former users and non-users (OR 1.12, n = 187).
Cannabis use increases the risk of non-adherence and quitting cannabis use may help adherence to antipsychotics. Thus, cannabis use may represent a potential target for intervention to improve medication adherence in those with psychosis.
Measles elimination goals have been adopted in a range of countries, sub-regions, and regions since the WHO declared an elimination goal by 2015 or 2020. All countries attempt to achieve and maintain high coverage through routine immunization programmes. This routine strategy, however, does not ensure the elimination goal of measles. Many developed countries, such as the United States, that have succeeded in interrupting measles transmission earlier, are now experiencing outbreaks with an increasing number of cases. Using a stochastic, age-structured model of measles vaccination dynamics, we explore and characterize the transient dynamics of measles susceptibility in the years following the implementation of routine vaccination at the herd immunity threshold. We demonstrate how a population could face risks of potentially large outbreaks even within few years of vaccination. We characterize different risk profiles depending on the incidence pattern in the years prior to vaccination. These results suggest that the classic critical vaccination threshold is necessary to achieve herd immunity, but not sufficient to prevent long periods of transient, super-critical dynamics. Our results suggest the need of future work for more careful monitoring of the impacts of current immunization programmes, and developing models that take into account more complicated vaccination strategies, demographic factors, and population movements.
Relapse in psychosis typically necessitates admission to hospital placing a significant financial burden on the health service. Exposure to childhood trauma is associated with an increased risk of psychosis, however, the extent to which this influences relapse is unclear. This report summarises current research investigating the influence of childhood trauma on relapse requiring psychiatric hospital admission for psychosis. Seven studies were included; two revealed a positive association between childhood trauma and relapse admission, two studies found a negative relationship and three found no significant difference. Inconsistent current evidence suggests a need for further research in this area.
Although the association between cannabis use and violence has been reported in the literature, the precise nature of this relationship, especially the directionality of the association, is unclear.
Young males from the Cambridge Study of Delinquent Development (n = 411) were followed up between the ages of 8 and 56 years to prospectively investigate the association between cannabis use and violence. A multi-wave (eight assessments, T1–T8) follow-up design was employed that allowed temporal sequencing of the variables of interest and the analysis of violent outcome measures obtained from two sources: (i) criminal records (violent conviction); and (ii) self-reports. A combination of analytic approaches allowing inferences as to the directionality of associations was employed, including multivariate logistic regression analysis, fixed-effects analysis and cross-lagged modelling.
Multivariable logistic regression revealed that compared with never-users, continued exposure to cannabis (use at age 18, 32 and 48 years) was associated with a higher risk of subsequent violent behaviour, as indexed by convictions [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.19–23.59] or self-reports (OR 8.9, 95% CI 2.37–46.21). This effect persisted after controlling for other putative risk factors for violence. In predicting violence, fixed-effects analysis and cross-lagged modelling further indicated that this effect could not be explained by other unobserved time-invariant factors. Furthermore, these analyses uncovered a bi-directional relationship between cannabis use and violence.
Together, these results provide strong indication that cannabis use predicts subsequent violent offending, suggesting a possible causal effect, and provide empirical evidence that may have implications for public policy.
In search of a suitable resource conservation technology under pigeonpea (Cajanus cajan L.)–wheat (Triticum aestivum L.) system in the Indo-Gangetic Plains, the effects of conservation agriculture (CA) on crop productivity and water-use efficiency (WUE) were evaluated during a 3-year study. The treatments were: conventional tillage (CT), zero tillage (ZT) with planting on permanent narrow beds (PNB), PNB with residue (PNB + R), ZT with planting on permanent broad beds (PBB) and PBB + R. The PBB + R plots had higher pigeonpea grain yield than the CT plots in all 3 years. However, wheat grain yields under all plots were similar in all years except for PBB + R plots in the second year, which had higher wheat yield than CT plots. The contrast analysis showed that pigeonpea grain yield of CA plots was significantly higher than CT plots in the first year. However, both pigeonpea and wheat grain yields during the last 2 years under CA and CT plots were similar. The PBB + R plots had higher system WUE than the CT plots in the second and third years. Plots under CA had significantly higher WUE and significantly lower water use than CT plots in these years. The PBB + R plots had higher WUE than PNB + R and PNB plots. Also, the PBB plots had higher WUE than PNB in the second and third years, despite similar water use. The interactions of bed width and residue management for all parameters in the second and third years were not significant. Those positive impacts under PBB + R plots over CT plots were perceived to be due to no tillage and significantly higher amount of estimated residue retention. Thus, both PBB and PBB + R technologies would be very useful under a pigeonpea–wheat cropping system in this region.
The aim of this article is to summarize current evidence regarding alterations in the neuroendocrine stress response system and endocannabinoid system and their relationship in psychotic disorders such as schizophrenia. Exposure to stress is linked to the development of a number of psychiatric disorders including psychosis. However, the precise role of stress in the development of psychosis and the possible mechanisms that might underlie this are not well understood. Recently the cannabinoid hypothesis of schizophrenia has emerged as a potential line of enquiry. Endocannabinoid levels are increased in patients with psychosis compared with healthy volunteers; furthermore, they increase in response to stress, which suggests another potential mechanism for how stress might be a causal factor in the development of psychosis. However, research regarding the links between stress and the endocannabinoid system is in its infancy. Evidence summarized here points to an alteration in the baseline tone and reactivity of the hypothalamic–pituitary–adrenal (HPA) axis as well as in various components of the endocannabinoid system in patients with psychosis. Moreover, the precise nature of the inter-relationship between these two systems is unclear in man, especially their biological relevance in the context of psychosis. Future studies need to simultaneously investigate HPA axis and endocannabinoid alterations both at baseline and following experimental perturbation in healthy individuals and those with psychosis to understand how they interact with each other in health and disease and obtain mechanistic insight as to their relevance to the pathophysiology of schizophrenia.
Effect of cannabis use on memory function is a contentious issue, with effects being different in healthy individuals and patients with psychosis.
Employing a meta-analytic approach we investigated the effects of cannabis use on memory function in patients with psychosis and healthy individuals, and the effect of diagnosis, memory dimension and moderating factors. A total of 88 studies were identified through a systematic literature search, investigating healthy (n = 7697) and psychotic (n = 3261) individuals. Standardized mean differences between the cannabis user and non-user groups on memory tasks were estimated using random-effects models and the effect-size statistic Cohen's d. Effects of potential moderating factors were tested using mixed-effects models and subgroup analyses.
We found that cannabis use was associated with significantly (p ⩽ 0.05) impaired global (d = 0.27) and prospective memory (d = 0.61), verbal immediate (d = 0.40) and delayed (d = 0.36) recall as well as visual recognition (d = 0.41) in healthy individuals, but a better global memory (d = −0.11), visual immediate recall (d = −0.73) and recognition (d = −0.42) in patients. Lower depression scores and younger age appeared to attenuate the effects of cannabis on memory. Cannabis-using patients had lower levels of depression and were younger compared with non-using patients, whilst healthy cannabis-users had higher depression scores than age-matched non-users. Longer duration of abstinence from cannabis reduced the effects on memory in healthy and patient users.
These results suggest that cannabis use is associated with a significant domain-specific impairment in memory in healthy individuals but not in cannabis-using patients, suggesting that they may represent a less developmentally impaired subgroup of psychotic patients.
Since early detection of pathogens and their virulence factors contribute to intervention and control strategies, we assessed the enteropathogens in diarrhoea disease and investigated the link between toxigenic strains of Escherichia coli from stool and drinking-water sources; and determined the expression of toxin genes by antibiotic-resistant E. coli in Lagos, Nigeria. This was compared with isolates from diarrhoeal stool and water from Wisconsin, USA. The new Luminex xTAG GPP (Gastroplex) technique and conventional real-time PCR were used to profile enteric pathogens and E. coli toxin gene isolates, respectively. Results showed the pathogen profile of stool and indicated a relationship between E. coli toxin genes in water and stool from Lagos which was absent in Wisconsin isolates. The Gastroplex technique was efficient for multiple enteric pathogens and toxin gene detection. The co-existence of antibiotic resistance with enteroinvasive E. coli toxin genes suggests an additional prognostic burden on patients.