Cannabis use and psychosis: a review of reviews Hasan, Alkomiet; von Keller, Rupert; Friemel, Chris Maria ...
European archives of psychiatry and clinical neuroscience,
06/2020, Letnik:
270, Številka:
4
Journal Article
Recenzirano
We conducted a systematic review of meta-analyses and systematic reviews to evaluate the impact of cannabis use on the onset and course of psychoses. Following a systematic literature search of five ...data bases (2005–2016) and consecutive structured evaluation, we were able to include 26 systematic reviews and meta-analyses. The methodological quality of the included publications were in the range of high and poor. The scientific literature indicates that psychotic illness arises more frequently in cannabis users compared to non-users, cannabis use is associated with a dose-dependent risk of developing psychotic illness, and cannabis users have an earlier onset of psychotic illness compared to non-users. Cannabis use was also associated with increased relapse rates, more hospitalizations and pronounced positive symptoms in psychotic patients. We make recommendations about the type of research that is required to better characterize the relationship between cannabis use and the development and outcomes of psychosis.
PURPOSE OF REVIEWThe most recent studies published or initiated in the last 18 months, investigating cannabidiol in the treatment of symptoms of schizophrenia and related conditions are summarized, ...including observed tolerability and reported side-effects.
RECENT FINDINGSRecent studies focused on patients with sub-acute psychotic syndromes of schizophrenia, clinical high-risk state for psychosis (CHR-P), or frequent cannabis users, as well as cognitive functioning in chronic schizophrenia. There is further, although not consistent evidence for cannabidiol-reducing positive symptoms, but not negative symptoms. Evidence for improvement of cognition was weaker, with one study reporting a worsening. Regarding side effects and tolerability, cannabidiol induced sedation in one study, with the other studies indicating good tolerability, even at high doses.
SUMMARYRecent clinical trials added further evidence for an antipsychotic potential of cannabidiol. In general, studies following trial designs as suggested by regulators in schizophrenia are needed in sufficient numbers to clarify the safety and efficacy of cannabidiol herein. In addition, such studies will further elucidate its ability to target specific aspects of the syndrome, such as negative or cognitive symptoms. Furthermore, aiming for an add-on treatment with cannabidiol will require further studies to identify potentially useful or even harmful combinations.
The endocannabinoid system shows promise as a novel target for treating psychiatric conditions. Cannabidiol (CBD), a naturally occurring cannabinoid, has been investigated in several psychiatric ...conditions, with diverse effects and an excellent safety profile compared to standard treatments. Even though the body of evidence from randomised clinical trials is growing, it remains relatively limited in most indications. This review comprises a comprehensive literature search to identify clinical studies on the effects of CBD in psychiatric conditions. The literature search included case studies, case reports, observational studies, and RCTs published in English before July 27, 2023, excluding studies involving nabiximols or cannabis extracts containing CBD and ∆
-tetrahydrocannabinol. Completed studies were considered, and all authors independently assessed relevant publications.Of the 150 articles identified, 54 publications were included, covering the effects of CBD on healthy subjects and various psychiatric conditions, such as schizophrenia, substance use disorders (SUDs), anxiety, post-traumatic stress disorder (PTSD), and autism spectrum disorders. No clinical studies have been published for other potential indications, such as alcohol use disorder, borderline personality disorder, depression, dementia, and attention-deficit/hyperactivity disorder. This critical review highlights that CBD can potentially ameliorate certain psychiatric conditions, including schizophrenia, SUDs, and PTSD. However, more controlled studies and clinical trials, particularly investigating the mid- to long-term use of CBD, are required to conclusively establish its efficacy and safety in treating these conditions. The complex effects of CBD on neural activity patterns, likely by impacting the endocannabinoid system, warrant further research to reveal its therapeutic potential in psychiatry.
There is epidemiological evidence that frequent cannabis use in general and during puberty in particular increases the risk to suffer psychosis and psychotic symptoms. Based on these observations, ...there is growing interest in the role of the endogenous cannabinoid system (eCB system) - the point of action for psychoactive cannabinoids - in psychiatric disorders and schizophrenia in particular. It has been hypothesized nearly two decades ago that the eCB system may play a pathophysiological role in schizophrenia either in terms of an endogenous malfunction of the system itself and/or of a secondary malfunction as a result of the use of exogenous cannabinoids like Δ(9)-tetrahydrocannabinol, the major psychoactive phytocannabinoid in Cannabis sativa. To test this hypothesis, several studies have been performed investigating endogenous ligands to cannabinoid CB1-receptors such as anandamide both in cerebrospinal fluid and plasma of patients and controls. Here a mini-review of the role of anandamide in schizophrenia is provided.
We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first ...episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64-90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ.
Summary
Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change. Consequently, the effects of ...adolescent‐onset mood and psychotic syndromes can have long term consequences.
A key clinical challenge for youth mental health is to develop and test new systems that align with current evidence for comorbid presentations and underlying neurobiology, and are useful for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care.
Our highly personalised and measurement‐based care model includes three core concepts:
▶ A multidimensional assessment and outcomes framework that includes: social and occupational function; self‐harm, suicidal thoughts and behaviour; alcohol or other substance misuse; physical health; and illness trajectory.
▶ Clinical stage.
▶ Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on proposed pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian).
The model explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology. Inherent within this highly personalised approach is the incorporation of other evidence‐based processes, including real‐time measurement‐based care as well as utilisation of multidisciplinary teams of health professionals.
Data‐driven local system modelling and personalised health information technologies provide crucial infrastructure support to these processes for better access to, and higher quality, mental health care for young people.
Chapter 1: Multidimensional outcomes in youth mental health care: what matters and why?
Mood and psychotic syndromes present one of the most serious public health challenges that we face in the 21st century. Factors including prevalence, age of onset, and chronicity contribute to substantial burden and secondary risks such as alcohol or other substance misuse.
Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change; thus, effects can have long term consequences.
We propose five key domains which make up a multidimensional outcomes framework that aims to address the specific needs of young people presenting to health services with emerging mental illness. These include social and occupational function; self‐harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory.
Impairment and concurrent morbidity are well established in young people by the time they present for mental health care. Despite this, services and health professionals tend to focus on only one aspect of the presentation — illness type, stage and trajectory — and are often at odds with the preferences of young people and their families.
There is a need to address the disconnect between mental health, physical health and social services and interventions, to ensure that youth mental health care focuses on the outcomes that matter to young people.
Chapter 2: Combining clinical stage and pathophysiological mechanisms to understand illness trajectories in young people with emerging mood and psychotic syndromes
Traditional diagnostic classification systems for mental disorders map poorly onto the early stages of illness experienced by young people, and purport categorical distinctions that are not readily supported by research into genetic, environmental and neurobiological risk factors.
Consequently, a key clinical challenge in youth mental health is to develop and test new classification systems that align with current evidence on comorbid presentations, are consistent with current understanding of underlying neurobiology, and provide utility for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care.
This chapter outlines a transdiagnostic framework for classifying common adolescent‐onset mood and psychotic syndromes, combining two independent but complementary dimensions: clinical staging, and three proposed pathophysiological mechanisms.
Clinical staging reflects the progression of mental disorders and is in line with the concept used in general medicine, where more advanced stages are associated with a poorer prognosis and a need for more intensive interventions with a higher risk‐to‐benefit ratio.
The three proposed pathophysiological mechanisms are neurodevelopmental abnormalities, hyperarousal and circadian dysfunction, which, over time, have illness trajectories (or pathways) to psychosis, anxious depression and bipolar spectrum disorders, respectively.
The transdiagnostic framework has been evaluated in young people presenting to youth mental health clinics of the University of Sydney's Brain and Mind Centre, alongside a range of clinical and objective measures. Our research to date provides support for this framework, and we are now exploring its application to the development of more personalised models of care.
Chapter 3: A comprehensive assessment framework for youth mental health: guiding highly personalised and measurement‐based care using multidimensional and objective measures
There is an urgent need for improved care for young people with mental health problems, in particular those with subthreshold mental disorders that are not sufficiently severe to meet traditional diagnostic criteria.
New comprehensive assessment frameworks are needed to capture the biopsychosocial profile of a young person to drive highly personalised and measurement‐based mental health care.
We present a range of multidimensional measures involving five key domains: social and occupational function; self‐harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory. Objective measures include: neuropsychological function; sleep–wake behaviours and circadian rhythms; metabolic and immune markers; and brain structure and function.
The recommended multidimensional measures facilitate the development of a comprehensive clinical picture. The objective measures help to further develop informative and novel insights into underlying pathophysiological mechanisms and illness trajectories to guide personalised care plans.
A panel of specific multidimensional and objective measures are recommended as standard clinical practice, while others are recommended secondarily to provide deeper insights with the aim of revealing alternative clinical paths for targeted interventions and treatments matched to the clinical stage and proposed pathophysiological mechanisms of the young person.
Chapter 4: Personalising care options in youth mental health: using multidimensional assessment, clinical stage, pathophysiological mechanisms, and individual illness trajectories to guide treatment selection
New models of mental health care for young people require that interventions be matched to illness type, clinical stage, underlying pathophysiological mechanisms and individual illness trajectories. Narrow syndrome‐focused classifications often direct clinical attention away from other key factors such as functional impairment, self‐harm and suicidality, alcohol or other substance misuse, and poor physical health.
By contrast, we outline a treatment selection guide for early intervention for adolescent‐onset mood and psychotic syndromes (ie, active treatments and indicated and more specific secondary prevention strategies). This guide is based on experiences with the Brain and Mind Centre's highly personalised and measurement‐based care model to manage youth mental health.
The model incorporates three complementary core concepts:
▶A multidimensional assessment and outcomes framework including: social and occupational function; self‐harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness trajectory.
▶Clinical stage.
▶Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on three underlying pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian).
These core concepts are not mutually exclusive and together may facilitate improved outcomes through a clinical stage‐appropriate and transdiagnostic framework that helps guide decisions regarding the provision of appropriate and effective care options.
Given its emphasis on adolescent‐onset mood and psychotic syndromes, the Brain and Mind Centre's model of care also respects a fundamental developmental perspective — categorising childhood problems (eg, anxiety and neurodevelopmental difficulties) as risk factors and respecting the fact that young people are in a period of major biological and social transition. Based on these factors, a range of social, psychological and pharmacological interventions are recommended, with an emphasis on balancing the personal benefit‐to‐cost ratio.
Chapter 5: A service delivery model to support highly personalised and measurement‐based care in youth mental health
Over the past decade, we have seen a growing focus on creating mental health service delivery models that better meet the unique needs of young Australians. Recent policy directives from the Australian Government recommend the adoption of stepped‐care services to improve the appropriateness of care, determined by severity of need.
Here, we propose that a highly personalised approach enhances stepped‐care models by incorporating clinical staging and a young person's current and multidimensional needs. It explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology.
Inherent within a highly personalised approach is the incorporation of other evidence‐based processes, including real‐time measurement‐based care and us
Abstract Over recent years, the interest in the endocannabinoid system (ECS) as a new target for the treatment of schizophrenia has evolved. The ECS represents one of the most relevant ...neurotransmitter systems in the brain and mainly fulfills a homeostatic role in terms of neurotransmission but also with respect to inflammatory processes. Two main approaches to the modulation of endocannabinoid functioning have been chosen so far. First, the selective blockade or inverse agonism of the type 1 cannabinoid receptor has been tested for the improvement of acute psychotic symptoms, as well as for the improvement of cognitive functions in schizophrenia. This was not effective in either case. Second, the modulation of endocannabinoid levels by use of the phytocannabinoid cannabidiol and selective fatty acid amide hydrolase inhibitors has been proposed, and the antipsychotic properties of cannabidiol are currently being investigated in humans. Unfortunately, for most of these trials that have focused on psychopathological and cognitive effects of cannabidiol, no published data are available. However, there is first evidence that cannabidiol may ameliorate psychotic symptoms with a superior side-effect profile compared with established antipsychotics. In conclusion, several clinical trials targeting the ECS in acute schizophrenia have either been completed or are underway. Although publicly available results are currently limited, preliminary data indicate that selected compounds modulating the ECS may be effective in acute schizophrenia. Nevertheless, so far, sample sizes of patients investigated are not sufficient to come to a final judgment, and no maintenance studies are available to ensure long-term efficacy and safety.
Obituary for Professor Hinderk Meiners Emrich, MD PhD Leweke, F. Markus; Bleich, Stefan; Schneider, Udo
European archives of psychiatry and clinical neuroscience,
12/2018, Letnik:
268, Številka:
8
Journal Article
Recenzirano
On 16 September 2018 Professor Hinderk Meiners Emrich, MD PhD, Emeritus Director of the Department of Psychiatry, Social Psychiatry and Psychotherapy of Hannover Medical School, passed away at the ...age of 75 years after a long illness.
Abstract The origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of ...low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies. The two cohorts were composed of the following: (1) n = 141 schizophrenia, n = 75 bipolar disorder, n = 78 controls; (2) n = 78 antipsychotic-naïve first-episode schizophrenia, n = 38 medicated first-episode schizophrenia. sCD14 seropositivity conferred a 3.1-fold increased odds of association with schizophrenia (multivariate regressions, OR = 3.09, p < 0.0001) compared to controls. Case–control differences in sCD14 were not matched by LBP. Quantitative levels of LBP, but not sCD14, correlated with BMI in schizophrenia (R2 = 0.21, p < 0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R2 = 0.26–0.27, p < 0.0001) and elevated in females compared to males (p < 0.01). Antipsychotic treatment generally did not impact sCD14 or LBP levels except for significant correlations, especially sCD14, with gluten antibodies in antipsychotic-naïve schizophrenia (R2 = 0.27, p < 0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R2 = 0.37, p < 0.001). In conclusion, these bacterial translocation markers produced discordant and complex patterns of activity, a finding that may reflect an imbalanced, activated innate immune state. Whereas both markers may upregulate following systemic exposure to Gram-negative bacteria, non-lipopolysaccharide-based monocyte activation, autoimmunity and metabolic dysfunction may also contribute to the observed marker profiles.
PURPOSE OF REVIEWThis review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression ...(unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use.
RECENT FINDINGSThere is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking. New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD.
SUMMARYThe most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.
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