Cannabis is a complex plant, with major compounds such as delta-9-tetrahydrocannabinol and cannabidiol, which have opposing effects. The discovery of its compounds has led to the further discovery of ...an important neurotransmitter system called the endocannabinoid system. This system is widely distributed in the brain and in the body, and is considered to be responsible for numerous significant functions. There has been a recent and consistent worldwide increase in cannabis potency, with increasing associated health concerns. A number of epidemiological research projects have shown links between dose-related cannabis use and an increased risk of development of an enduring psychotic illness. However, it is also known that not everyone who uses cannabis is affected adversely in the same way. What makes someone more susceptible to its negative effects is not yet known, however there are some emerging vulnerability factors, ranging from certain genes to personality characteristics. In this article we first provide an overview of the biochemical basis of cannabis research by examining the different effects of the two main compounds of the plant and the endocannabinoid system, and then go on to review available information on the possible factors explaining variation of its effects upon different individuals.
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.
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.
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.
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.
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).
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.
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 first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in ...early psychosis.
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.
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).
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.
Abstract 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.
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.
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.
Cannabis is the most widely used illicit substance in the world and due to the high levels of use observed among young people with psychosis, most research has focused on the causal relationship ...between cannabis use and mental health problems. Despite a large interest in developing intervention models to target this group, there are as yet no established and effective methods of prevention and intervention focusing on cannabis use. In this paper we present the available evidence for the effectiveness of substance use treatments in patients with co-morbid severe mental illness, as well as exploring the prevention and early intervention initiatives for substance use in the general population.
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