Dietary intake, physical activity and sedentary behaviour patterns in a sample with established psychosis and associations with mental health symptomatology.

BACKGROUND: People with psychosis experience cardiometabolic comorbidities, including metabolic syndrome, coronary heart disease and diabetes. These physical comorbidities have been linked to diet, inactivity and the effects of the illness itself, including disorganisation, impairments in global function and amotivation associated with negative symptoms of schizophrenia or co-morbid depression. METHODS: We aimed to describe the dietary intake, physical activity (PA) and sedentary behaviour patterns of a sample of patients with established psychosis participating in the Improving Physical Health and Reducing Substance Use in Severe Mental Illness (IMPaCT) randomised controlled trial, and to explore the relationship between these lifestyle factors and mental health symptomatology. RESULTS: A majority of participants had poor dietary quality, low in fruit and vegetables and high in discretionary foods. Only 29.3% completed ⩾150 min of moderate and/or vigorous activity per week and 72.2% spent ⩾6 h per day sitting. Cross-sectional associations between negative symptoms, global function, and PA and sedentary behaviour were observed. Additionally, those with more negative symptoms receiving IMPaCT therapy had fewer positive changes in PA from baseline to 12-month follow-up than those with fewer negative symptoms at baseline. CONCLUSION: These results highlight the need for the development of multidisciplinary lifestyle and exercise interventions to target eating habits, PA and sedentary behaviour, and the need for further research on how to adapt lifestyle interventions to baseline mental status. Negative symptoms in particular may reduce patient's responses to lifestyle interventions.

Predictive value of cardiometabolic biomarkers and depressive symptoms for symptom severity and quality of life in patients with psychotic disorders.

BACKGROUND: Patients with psychotic disorders show higher rates of the metabolic syndrome (MS) between the cluster of severe mental illnesses. Depressive symptoms can worsen outcomes of individuals with psychotic disorders. However, research on the association between MS and depression in psychotic disorders and their relevance to outcomes is lacking. METHODS: We investigated the association between depression and cardiometabolic biomarkers in psychotic disorders and the predictive value of depressive symptoms on psychopathological severity and quality of life (QoL). 406 patients with psychotic disorders were recruited as part of the Improving Physical Health and Reducing Substance Use in Severe Mental Illness randomised controlled trial. Depression, psychotic symptoms, QoL, waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), blood pressure, and fasting glucose of patients were assessed at baseline and 12 months. Sensitivity analyses were conducted to test the effect of treatment. RESULTS: More severe baseline symptoms of depression significantly predicted worse 12-month psychotic symptoms and lower mental health related QoL at 12 months. These associations held after controlling for alcohol use, gender, ethnicity, education, and mental health related QoL Baseline. Depressive symptoms also correlated with waist circumference at both baseline and 12 months, after controlling for multiple testing. CONCLUSION: Individuals with psychotic disorders experiencing more severe depressive symptoms are more likely to have larger waist circumference contemporaneously and 12 months later, as well as more severe psychotic symptoms and worse QoL at follow-up. This highlights the need for evaluation of strategies to address depression in the management of psychotic disorders.

Effect of lifestyle, medication and ethnicity on cardiometabolic risk in the year following the first episode of psychosis: prospective cohort study.

BACKGROUND: The first episode of psychosis is a critical period in the emergence of cardiometabolic risk. AIMS: We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis. METHOD: This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months. RESULTS: Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol). CONCLUSIONS: Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Tobacco smoking and nicotine dependence in first episode and established psychosis.

AIM: People with psychotic disorders have increased premature mortality in comparison with the general population, with high rates of cigarette use a contributing factor. We aimed to describe the prevalence of cigarette use and nicotine dependence (ND) in first episode psychosis (FEP), and established psychosis; and to investigate associations between clinical symptoms and ND. METHODOLOGY: Smoking and clinical data were collected from two cohorts: 181 people with FEP recruited as part of the Physical Health and Substance Use Measures in First Onset Psychosis (PUMP) study and from 432 people with established psychosis recruited as part of the Improving physical health and reducing substance use in psychosis randomised controlled trial (IMPaCT RCT). RESULTS: The prevalence of cigarette smoking was 78% in FEP and 62% in established psychosis. Forty nine percent (n = 60) of smokers in the FEP cohort and 69% (n = 183) of smokers with established psychosis were highly nicotine dependent. Being a highly nicotine dependent smoker was significantly associated with higher PANSS positive symptom scores (F = 5.480 p = 0.004), and with decreased scores on the Rosenberg self-esteem scale (F = 3.261, p = 0.039) in established psychosis. There was no diagnostic specificity identified in relation to smoking or ND in both groups. CONCLUSION: High rates of cigarette usage and nicotine dependence are problems from the early stages of psychosis. ND is higher in people with established psychosis. Smoking cessation strategies as part of comprehensive management of psychotic disorders at every stage require further development and evaluation.

Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of δ-9-THC.

BACKGROUND: Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear. METHODS: We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomized, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n = 14) following THC administration and those who did not (NP; n = 22). RESULTS: Under placebo conditions, there was significantly greater engagement of the left hippocampus (p < 0.001) in the TP group compared with the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (Spearman's ρ = 0.44, p = 0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC. CONCLUSIONS: These results suggest that altered hippocampal activation during verbal encoding may serve as a marker of sensitivity to the acute psychotomimetic effects of THC.

Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT).

BACKGROUND: People with psychosis have a reduced life expectancy of 10-20 years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. METHODS: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. RESULTS: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15 months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p = 0.034). The 22% of patients who received >180 min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. CONCLUSION: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. TRIAL REGISTRATION: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926 .

Randomised controlled trial to improve health and reduce substance use in established psychosis (IMPaCT): cost-effectiveness of integrated psychosocial health promotion.

BACKGROUND: There is mounting evidence that people with severe mental illness have unhealthy lifestyles, high rates of cardiovascular and metabolic diseases, and greater risk of early mortality. This study aimed to assess the cost-effectiveness of a health promotion intervention seeking to improve physical health and reduce substance use in people with psychosis. METHODS: Participants with a psychotic disorder, aged 18-65 years old and registered on an enhanced care approach programme or equivalent were recruited from community mental health teams in six mental health trusts in England. Participants were randomisation to either standard community mental health team care (treatment as usual) or treatment as usual with an integrated health promotion intervention (IMPaCT). Cost-effectiveness and cost-utility analyses from health and social care and societal perspectives were conducted alongside a cluster randomised controlled trial. Total health and social care costs and total societal costs at 12 and 15 months were calculated as well as cost-effectiveness (incremental cost-effectiveness ratios and cost-effectiveness acceptability curves) at 15 months based on quality of life (SF-36 mental and physical health components, primary outcome measures) and quality adjusted life years (QALYs) using two measures, EQ-5D-3 L and SF-36. Data were analysed using bootstrapped regressions with covariates for relevant baseline variables. RESULTS: At 12-15 months 301 participants had full data needed to be included in the economic evaluation. There were no differences in adjusted health and social care costs (£95, 95% CI -£1410 to £1599) or societal costs (£675, 95% CI -£1039 to £2388) between the intervention and control arms. Similarly, there were no differences between the groups in the SF-36 mental component (-0.80, 95% CI -3.66 to 2.06), SF-36 physical component (-0.68, 95% CI -3.01 to 1.65), QALYs estimated from the SF-36 (-0.00, -0.01 to 0.00) or QALYs estimated from the EQ-5D-3 L (0.00, 95% CI -0.01 to 0.02). Cost-effectiveness acceptability curves for all four outcomes and from both cost perspectives indicate that the probability of the health promotion intervention being cost-effective does not exceed 0.4 for willingness to pay thresholds ranging from £0-£50,000. CONCLUSIONS: Alongside no evidence of additional quality of life/clinical benefit, there is also no evidence of cost-effectiveness. TRIAL REGISTRATION: ISRCTN58667926 . Date retrospectively registered: 23/04/2010. Recruitment start date: 01/03/2010.

Hyperprolactinaemia in first episode psychosis - A longitudinal assessment.

Little is known about hyperprolactinaemia (HPL) in first episode psychosis (FEP) patients. We investigated longitudinal changes in serum prolactin in FEP, and the relationship between HPL, and antipsychotic medication and stress. Serum prolactin was recorded in FEP patients at recruitment and again, 3 and 12months later. HPL was defined as a serum prolactin level >410mIU/L (~19.3ng/ml) for males, and a serum prolactin level >510mIU/L (~24.1ng/ml) for females. From a total of 174 people with serum prolactin measurements at study recruitment, 43% (n=74) had HPL, whilst 27% (n=21/78) and 27% (n=26/95) had HPL at 3 and 12months respectively. We observed higher serum prolactin levels in females versus males (p<0.001), and in antipsychotic treated (n=68) versus antipsychotic naïve patients (p<0.0001). Prolactin levels were consistently raised in FEP patients taking risperidone, amisulpride and FGAs compared to other antipsychotics. No significant relationship was observed between perceived stress scores (ß=7.13, t=0.21, df=11, p=0.0.84 95% CI -72.91-87.16), or objective life stressors (ß=-21.74, t=-0.31, df=8, p=0.77 95% CI -218.57-175.09) and serum prolactin. Our study found elevated rates of HPL over the course of the first 12months of illness. We found no evidence to support the notion that stress is related to elevated serum prolactin at the onset of psychosis.

An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis.

BACKGROUND: Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses. METHODS: The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis. RESULTS: PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10-6), but lower in individuals of African ancestry (R2 = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2 = 9.2%, p = .002). CONCLUSIONS: PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP.

The effect of five day dosing with THCV on THC-induced cognitive, psychological and physiological effects in healthy male human volunteers: A placebo-controlled, double-blind, crossover pilot trial.

RATIONALE: Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC. OBJECTIVES: To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers. METHODS: Ten male cannabis users (<25 use occasions) were recruited for this within-subjects, placebo-controlled, double-blind, cross-over pilot study. 10mg oral pure THCV or placebo were administered daily for five days, followed by 1mg intravenous THC on the fifth day. RESULTS: THCV was well tolerated and subjectively indistinguishable from placebo. THC did not significantly increase psychotic symptoms, paranoia or impair short-term memory, while still producing significant intoxicating effects. Delayed verbal recall was impaired by THC and only occurred under placebo condition (Z=-2.201, p=0.028), suggesting a protective effect of THCV. THCV also inhibited THC-induced increased heart rate (Z=-2.193, p=0.028). Nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense (χ(2)=6.4, p=0.011). THCV in combination with THC significantly increased memory intrusions (Z=-2.155, p=0.031). CONCLUSION: In this first study of THC and THCV, THCV inhibited some of the well-known effects of THC, while potentiating others. These findings need to be interpreted with caution due to a small sample size and lack of THC-induced psychotomimetic and memory-impairing effect, probably owing to the choice of dose.

Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study.

BACKGROUND: The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. METHODS: We applied adjusted logistic regression models to data from patients aged 18-65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. FINDINGS: Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52-3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81-11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17-31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. INTERPRETATION: The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. FUNDING: UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at King's College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]).

Cannabinoid modulation of functional connectivity within regions processing attentional salience.

There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.

Time perception networks and cognition in schizophrenia: a review and a proposal.

Timing is an essential function for the survival of many living organisms. Despite its significance, it is relatively under-researched, particularly in schizophrenia. We examined neurophysiological, neuropathological, imaging and genetic studies of both healthy subjects and subjects suffering from schizophrenia in relation to time perception as measured by interval timing. We found that the data from studies in healthy populations indicate that time perception may be inter-linked with numerous other cognitive functions and share common brain networks. The same networks are implicated in the pathophysiology of schizophrenia. There is also evidence that several neurotransmitter systems, particularly the dopaminergic D2 system, are involved in interval timing. Patients with schizophrenia have been shown to suffer from a distorted sense of time, which has an impact on their cognitive function and results in both positive and negative symptoms. Therefore, genes involved in interval timing can be considered candidate genes for distorted cognition in schizophrenia. We discuss the hypothesis that time perception dysfunction is a primary cognitive dysfunction in schizophrenia.

Improving physical health and reducing substance use in psychosis--randomised control trial (IMPACT RCT): study protocol for a cluster randomised controlled trial.

BACKGROUND: Cardiovascular morbidity and mortality is increased in individuals with severe mental illnesses.We set out to establish a multicentre, two arm, parallel cluster randomized controlled trial (RCT) of a health promotion intervention (HPI), IMPACT Therapy. The patient-tailored IMPACT Therapy aims to target one or more health behaviours from a pre-defined list that includes cannabis use; alcohol use; other substance use; cigarette smoking; exercise; diet and diabetic control, prioritising those identified as problematic by the patient, taking a motivational interviewing and CBT approach. METHODS: Impact therapy will be delivered by care coordinators in the community to the treatment group and will be compared to treatment as usual (TAU). The main hypothesis is that the addition of IMPACT Therapy (HPI) to TAU will be more effective than TAU alone in improving patients' quality of life as measured by the Short Form-36, including mental health and physical health subscales on completion of the intervention at 12 months post randomisation. A subsidiary hypothesis will be that addition of IMPACT Therapy (HPI) will be more cost-effective than TAU alone in improving health in people with SMI 12 months from baseline. The IMPACT therapy patient groups' improvement in quality of life, as well as its cost effectiveness, is hypothesised to be maintained at 15 months. Outcomes will be analyzed on an intention-to-treat (ITT) basis. DISCUSSION: The results of the trial will provide information about the effectiveness of the IMPACT therapy programme in supporting community mental health teams to address physical comorbidity in severe mental illness. TRIAL REGISTRATION: ISRCTN58667926.

Is cannabis neurotoxic for the healthy brain? A meta-analytical review of structural brain alterations in non-psychotic users.

AIMS: Despite growing research in the field of cannabis imaging, mostly in those with a psychotic illness, the possible neurotoxic effects of smoked cannabis on the healthy brain have yet to be fully understood. There appears to be a need to evaluate the existing imaging data on the neuroanatomical effects of cannabis use on non-psychotic populations. METHODS: We conducted a meta-analytical review to estimate the putative neurotoxic effect of cannabis in non-psychotic subjects who were using or not using cannabis. We specifically tested the hypothesis that cannabis use can alter grey and white matter in non-psychotic subjects. RESULTS: Our systematic literature search uncovered 14 studies meeting the inclusion criteria for the meta-analysis. The overall database comprised 362 users and 365 non-users. At the level of the individual studies there is limited and contrasting evidence supporting a cannabis-related alteration on the white and grey matter structures of non-psychotic cannabis users. However, our meta-analysis showed a consistent smaller hippocampus in users as compared to non-users. Heterogeneity across study designs, image acquisition, small sample sizes and limited availability of regions of interest to be included in the meta-analysis may undermine the core findings of this study. CONCLUSIONS: Our results suggest that in the healthy brain, chronic and long-term cannabis exposure may exert significant effects in brain areas enriched with cannabinoid receptors, such as the hippocampus, which could be related to a neurotoxic action.

The effect of cannabis on perception of time: a critical review.

The survival of any organism, animal or human, relies on the ability to accurately process, sense or tell time. Emerging evidence shows that timing is a crucial element in most, if not all, cognitive functioning and motor behaviour. Advances made by timing researchers provide valuable information on the neural substrates of interval timing, which indicate the involvement of certain brain areas and networks, most of which have not only been implicated in conditions such as schizophrenia, but are also abundant with cannabinoid receptors. A distorted sense of time is one of the most common effects of cannabis reported by users. In this paper, we present a critical review of the existing research on the topic. The findings are inconclusive, mainly due to methodological variations and the paucity of research. Even though 70% of time estimation studies report over-estimation, the findings of time production and time reproduction studies remain inconclusive. More research with robust methods is required to reach conclusions about the precise effect of cannabis and its active compounds on time perception. Such studies may also lead towards a better understanding of the mechanisms involved in brain functioning.

Neural mechanisms for the cannabinoid modulation of cognition and affect in man: a critical review of neuroimaging studies.

Pharmacological challenge in conjunction with neuroimaging techniques has been employed for over two decades now to understand the neural basis of the cognitive, emotional and symptomatic effects of the main ingredients of cannabis, the most widely used illicit drug in the world. This selective critical review focuses on the human neuroimaging studies investigating the effects of delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD), the two main cannabinoids of interest present in the extract of the cannabis plant. These studies suggest that consistent with the polymorphic and heterogeneous nature of the effects of cannabis, THC and CBD have distinct and often opposing effects on widely distributed neural networks that include medial temporal and prefrontal cortex and striatum, brain regions that are rich in cannabinoid receptors and implicated in the pathophysiology of psychosis. They help elucidate the neurocognitive mechanisms underlying the acute induction of psychotic symptoms by cannabis and provide mechanistic understanding underlying the potential role of CBD as an anxiolytic and antipsychotic. Although there are ethical and methodological caveats, pharmacological neuroimaging studies such as those reviewed here may not only help model different aspects of the psychopathology of mental disorders such as schizophrenia and offer insights into their underlying mechanisms, but may suggest potentially new therapeutic targets for drug discovery.

Why do psychotic patients use cannabis? Case series.

The rate of substance use, particularly cannabis, among patients with psychosis is high and much greater than in the general population. Persistent cannabis use by patients with an established psychotic disorder adversely affects prognosis and recovery. Little agreement has been reached on the reasons that sustain cannabis use in patients with psychosis although self-report studies have shown that patients appear to use cannabis largely for the same reasons as the general population i.e. to 'get high' or reduce negative states such as depression and boredom. The aim of this series is to explore 5 individual cases of patients with psychosis reporting cannabis use. Full clinical assessment for each patient as well as cannabis use history, reasons for use and implications for effective treatment are explored.

A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation.

Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the main compound of the Cannabis Sativa responsible for most of the effects of the plant. Another major constituent is cannabidiol (CBD), formerly regarded to be devoid of pharmacological activity. However, laboratory rodents and human studies have shown that this cannabinoid is able to prevent psychotic-like symptoms induced by high doses of Δ(9)- THC. Subsequent studies have demonstrated that CBD has antipsychotic effects as observed using animal models and in healthy volunteers. Thus, this article provides a critical review of the research evaluating antipsychotic potential of this cannabinoid. CBD appears to have pharmacological profile similar to that of atypical antipsychotic drugs as seem using behavioral and neurochemical techniques in animal models. Additionally, CBD prevented human experimental psychosis and was effective in open case reports and clinical trials in patients with schizophrenia with a remarkable safety profile. Moreover, fMRI results strongly suggest that the antipsychotic effects of CBD in relation to the psychotomimetic effects of Δ(9)-THC involve the striatum and temporal cortex that have been traditionally associated with psychosis. Although the mechanisms of the antipsychotic properties are still not fully understood, we propose a hypothesis that could have a heuristic value to inspire new studies. These results support the idea that CBD may be a future therapeutic option in psychosis, in general and in schizophrenia, in particular.

Pharmacological interventions in the treatment of the acute effects of cannabis: a systematic review of literature.

BACKGROUND: Cannabis intoxication is related to a number of physical and mental health risks with ensuing social costs. However, little attention has been given to the investigation of possible pharmacological interactions in this condition. OBJECTIVE: To review the available scientific literature concerning pharmacological interventions for the treatment of the acute effects of cannabis. METHODS: A search was performed on the Pubmed, Lilacs, and Scielo online databases by combining the terms cannabis, intoxication, psychosis, anxiety, and treatment. The articles selected from this search had their reference lists checked for additional publications related to the topic of the review. RESULTS: The reviewed articles consisted of case reports and controlled clinical trials and are presented according to interventions targeting the physiological, psychiatric, and cognitive symptoms provoked by cannabis. The pharmacological interventions reported in these studies include: beta-blockers, antiarrhythmic agents, antagonists of CB-1 and GABA-benzodiazepine receptors, antipsychotics, and cannabidiol. CONCLUSION: Although scarce, the evidence on pharmacological interventions for the management of cannabis intoxication suggests that propanolol and rimonabant are the most effective compounds currently available to treat the physiological and subjective effects of the drug. Further studies are necessary to establish the real effectiveness of these two medications, as well as the effectiveness of other candidate compounds to counteract the effects of cannabis intoxication, such as cannabidiol and flumazenil.