Cannabis use predicts future psychotic symptoms, and vice versa

Abstract Cannabis is the most widely used illicit drug worldwide, and it is estimated that up to 30% of people who use cannabis will develop a cannabis use disorder (CUD). Demand for treatment of CUD is increasing in almost every region of the world and cannabis use is highly comorbid with mental disorders, where sustained use can reduce treatment compliance and increase risk of relapse. In this narrative review, we outline evidence for psychosocial and pharmacological treatment strategies for CUD, both alone and when comorbid with psychosis, anxiety or depression. Psychosocial treatments such as cognitive behavioural therapy, motivational enhancement therapy and contingency management are currently the most effective strategy for treating CUD but are of limited benefit when comorbid with psychosis. Pharmacological treatments targeting the endocannabinoid system have the potential to reduce cannabis withdrawal and cannabis use in CUD. Mental health comorbidities including anxiety, depression and psychosis hinder effective treatment and should be addressed in treatment provision and clinical decision making to reduce the global burden of CUDs. Antipsychotic medication may decrease cannabis use and cannabis craving as well as psychotic symptoms in patients with CUD and psychosis. Targeted treatments for anxiety and depression when comorbid with CUD are feasible.

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Aberrant Salience among Young Healthy Postgraduate University Students: The Role of Cannabis Use, Psychotic-Like Experiences, and Personality

Psychopathology ◽

10.1159/000520331 ◽

2022 ◽

pp. 1-7

Author(s):

Andrea Patti ◽

Gabriele Santarelli ◽

Giulio D’Anna ◽

Andrea Ballerini ◽

Valdo Ricca

Keyword(s):

University Students ◽

Personality Traits ◽

Cannabis Use ◽

Positive Symptom ◽

Psychotic Symptoms ◽

Symptom Frequency ◽

Character Inventory ◽

Aberrant Salience ◽

Self Transcendence

Aberrant salience (AS) is an anomalous world experience which plays a major role in psychotic proneness. In the general population, a deployment of this construct – encompassing personality traits, psychotic-like symptoms, and cannabis use – could prove useful to outline the relative importance of these factors. For this purpose, 106 postgraduate university students filled the AS Inventory (ASI), the Community Assessment of Psychic Experiences (CAPE), the Temperament and Character Inventory (TCI), and the Symptom Checklist 90-Revised (SCL-90-R). Lifetime cannabis users (<i>n</i> = 56) and individuals who did not use cannabis (<i>n</i> = 50) were compared. The role of cannabis use and psychometric indexes on ASI total scores was tested in different subgroups (overall sample, cannabis users, and nonusers). The present study confirmed that cannabis users presented higher ASI scores. The deployment of AS proved to involve positive symptom frequency (assessed through CAPE), character dimensions of self-directedness and self-transcendence (TCI subscales), and cannabis use. Among nonusers, the role of personality traits (assessed through the TCI) was preeminent, whereas positive psychotic-like experiences (measured by means of CAPE) had a major weight among cannabis users. The present study suggests that pre-reflexive anomalous world experiences such as AS are intertwined with reflexive self-consciousness, personality traits, current subclinical psychotic symptoms, and cannabis use. In the present study, subthreshold psychotic experiences proved to play a major role among cannabis users, whereas personality appeared to be more relevant among nonusers.

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Cannabis use and first-episode psychosis: relationship with manic and psychotic symptoms, and with age at presentation

Psychological Medicine ◽

10.1017/s0033291713000883 ◽

2013 ◽

Vol 44 (3) ◽

pp. 499-506 ◽

Cited By ~ 40

Author(s):

J. M. Stone ◽

H. L. Fisher ◽

B. Major ◽

B. Chisholm ◽

J. Woolley ◽

...

Keyword(s):

Longitudinal Design ◽

First Episode Psychosis ◽

Cannabis Use ◽

Daily Functioning ◽

Psychotic Symptoms ◽

First Episode ◽

Time Points ◽

Manic Symptoms ◽

Episode Psychosis ◽

Early Intervention In Psychosis

BackgroundCannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms.MethodClinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points – at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded.ResultsLevel of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up.ConclusionsEffective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.

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Cannabis and psychosis: revisiting a nineteenth century study of ‘Indian Hemp and Insanity’ in Colonial British India

Psychological Medicine ◽

10.1017/s0033291719001077 ◽

2019 ◽

Vol 50 (7) ◽

pp. 1164-1172 ◽

Cited By ~ 2

Author(s):

Oyedeji A. Ayonrinde

Keyword(s):

Nineteenth Century ◽

Mental Illness ◽

Current Knowledge ◽

Cannabis Use ◽

Mental Illnesses ◽

Current Evidence ◽

Psychotic Symptoms ◽

British India ◽

Indian Hemp ◽

Commission Report

AbstractBackgroundIn nineteenth-century British India, concern regarding large numbers of asylum patients with ‘Indian Hemp Insanity’ led to establishment of the Indian Hemp Drugs Commission. The exotic cannabis plant was widely used in pharmacopeia and a source of government revenue. The Commission was tasked with determining the public health risks of cannabis use, particularly mental illness. This analysis of the Commission report seeks to highlight the status of 1892 cannabis research and compare it with current evidence for medical and recreational cannabis use.MethodsDetailed historiographic review of the Indian Hemp Drugs Commission Report (1892).ResultsIn 1892, heavy cannabis use was considered to have been associated with severe mental illness (7.3% of asylum patients; 12.6% of patients with diagnoses). About two-thirds were children and young adults with higher relapse rates. Risk increased with early cannabis use and a family history of mental illness. Cannabis psychosis was found to have a shorter trajectory and better prognosis than other mental illnesses in the asylums. Different cannabis potency and modes of consumption had different effects. Occasional cannabis use was felt to have medicinal benefits for some. Appendices provided symptoms and demographic characteristics of cannabis-induced mental illness.ConclusionThis important nineteenth-century study observed frequency and dose-related effects of cannabis on mental health, particularly psychotic symptoms in young people with a previous or hereditary risk of mental illness. Pathophysiological observations were consistent with current knowledge. As one of the most systematic and detailed studies of the effects of cannabis of the time it foreshadowed contemporary cannabis issues.

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Cannabis consumption and psychosis or schizophrenia development

International Journal of Social Psychiatry ◽

10.1177/0020764018801690 ◽

2018 ◽

Vol 64 (7) ◽

pp. 690-704 ◽

Cited By ~ 11

Author(s):

María Bettina Ortiz-Medina ◽

Marta Perea ◽

Julio Torales ◽

Antonio Ventriglio ◽

Giovanna Vitrani ◽

...

Keyword(s):

Cannabis Use ◽

Psychotic Symptoms ◽

Current State ◽

Gene Environment ◽

Pubmed Database ◽

Increased Risk ◽

Vulnerable People ◽

Cannabis Consumption ◽

The Relationship

Objective: Cannabis consumption produces psychopathology, in some cases psychotic episodes, which are of our interest in this work. However, the relationship between cannabis use and psychosis has not been fully elucidated. The objectives of this work are to (1) review the current state of knowledge on the association of cannabis use with the risk of the development of psychosis or psychotic symptoms in people without schizophrenia and (2) assess the consistency of the hypothesis that cannabis use is associated with increased risk of psychosis in people without schizophrenia. Method: This work included research done in humans until May 2018 with the keywords ‘cannabis’ and ‘psychosis’, published in English and Spanish, in the PubMed database. Results: In all, 66 papers were analyzed, of which 23 were cohort trials and 43 were reviews. Conclusion: Cannabis use doubles the risk of developing psychosis in vulnerable people. There even exists a relationship regarding the dose used and the age of first use. Gene–environment interactions that modulate the association between cannabis use and the presence of psychosis have also been described.

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Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms

The British Journal of Psychiatry ◽

10.1192/bjp.bp.112.121178 ◽

2013 ◽

Vol 202 (5) ◽

pp. 381-382 ◽

Cited By ~ 51

Author(s):

Celia J. A. Morgan ◽

Emma Page ◽

Carola Schaefer ◽

Katharine Chatten ◽

Amod Manocha ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Lower Risk ◽

Endocannabinoid System ◽

Cannabis Use ◽

Psychotic Symptoms ◽

Csf Levels ◽

Drug Free

SummaryAnandamide is a ligand of the endocannabinoid system. Animals show a depletion following repeated Δ9-tetrahydrocannabinol (THC) administration but the effect of cannabis use on central nervous system levels of endocannabinoids has not been previously examined in humans. Cerebrospinal fluid (CSF) levels of the endocannabinoids anandamide, 2-arachidonoylglycerol (2-AG) and related lipids were tested in 33 volunteers (20 cannabis users). Lower levels of CSF anandamide and higher levels of 2-AG in serum were observed in frequent compared with infrequent cannabis users. Levels of CSF anandamide were negatively correlated with persisting psychotic symptoms when drug-free. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use.

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Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence

Psychological Medicine ◽

10.1017/s0033291709991966 ◽

2009 ◽

Vol 40 (10) ◽

pp. 1627-1634 ◽

Cited By ~ 96

Author(s):

M. Harley ◽

I. Kelleher ◽

M. Clarke ◽

F. Lynch ◽

L. Arseneault ◽

...

Keyword(s):

Childhood Trauma ◽

Substance Misuse ◽

Psychiatric Symptoms ◽

Population Based ◽

Cannabis Use ◽

School Age Children ◽

Psychotic Symptoms ◽

Vulnerable Group ◽

Additive Interaction ◽

Population Based Study

BackgroundAdolescent cannabis use has been shown in many studies to increase the risk of later psychosis. Childhood trauma is associated with both substance misuse and risk for psychosis. In this study our aim was to investigate whether there is a significant interaction between cannabis use and childhood trauma in increasing the risk for experiencing psychotic symptoms during adolescence.MethodPsychiatric interviews using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) semi-structured instrument were carried out with 211 adolescents aged between 12 and 15 years and their parents as part of a population-based study. The interview enquired about early traumatic events, cannabis use and psychiatric symptoms in adolescence.ResultsIn separate analyses both cannabis use and childhood trauma were significantly associated with risk of experiencing psychotic symptoms. However, the presence of both childhood trauma and early cannabis use significantly increased the risk for psychotic symptoms beyond the risk posed by either risk factor alone, indicating that there was a greater than additive interaction between childhood trauma and cannabis use.ConclusionOur finding of a greater than additive interaction between childhood trauma and cannabis use may have implications for the identification of individuals at high risk of experiencing psychotic symptoms. For example, measures to actively discourage or intensively treat cannabis use in children and adolescents who have experienced abuse may help to prevent the development of psychosis in this vulnerable group. Our findings require replication in larger samples to confirm this interaction effect.

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Replication in two independent population-based samples that childhood maltreatment and cannabis use synergistically impact on psychosis risk

Psychological Medicine ◽

10.1017/s0033291711000973 ◽

2011 ◽

Vol 42 (1) ◽

pp. 149-159 ◽

Cited By ~ 63

Author(s):

M. Konings ◽

N. Stefanis ◽

R. Kuepper ◽

R. de Graaf ◽

M. ten Have ◽

...

Keyword(s):

Childhood Maltreatment ◽

Composite International Diagnostic Interview ◽

Population Based ◽

Diagnostic Interview ◽

Study Data ◽

Cannabis Use ◽

Psychotic Symptoms ◽

Data Sets ◽

Independent Population ◽

Study Test

BackgroundThere may be biological plausibility to the notion that cannabis use and childhood trauma or maltreatment synergistically increase the risk for later development of psychotic symptoms. To replicate and further investigate this issue, prospective data from two independent population-based studies, the Greek National Perinatal Study (n=1636) and The Netherlands Mental Health Survey and Incidence Study (NEMESIS) (n=4842), were analyzed.MethodTwo different data sets on cannabis use and childhood maltreatment were used. In a large Greek population-based cohort study, data on cannabis use at age 19 years and childhood maltreatment at 7 years were assessed. In addition, psychotic symptoms were assessed using the Community Assessment of Psychic Experiences (CAPE). In NEMESIS, the Composite International Diagnostic Interview (CIDI) was used to assess psychotic symptoms at three different time points along with childhood maltreatment and lifetime cannabis use.ResultsA significant adjusted interaction between childhood maltreatment and later cannabis use was evident in both samples, indicating that the psychosis-inducing effects of cannabis were stronger in individuals exposed to earlier sexual or physical mistreatment [Greek National Perinatal Study: test for interactionF(2, 1627)=4.18,p=0.02; NEMESIS: test for interaction χ2(3)=8.08,p=0.04].ConclusionsCross-sensitivity between childhood maltreatment and cannabis use may exist in pathways that shape the risk for expression of positive psychotic symptoms.

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Schizophrenia polygenic risk score and cannabis use modify psychosis expression in first episode psychosis patients and population controls

10.1101/19013284 ◽

2019 ◽

Author(s):

Diego Quattrone ◽

Ulrich Reininghaus ◽

Alex L. Richards ◽

Giada Tripoli ◽

Laura Ferraro ◽

...

Keyword(s):

Continuous Distribution ◽

First Episode Psychosis ◽

Cannabis Use ◽

Psychotic Symptoms ◽

First Episode ◽

Polygenic Risk Score ◽

Small Magnitude ◽

Polygenic Risk ◽

Episode Psychosis ◽

Population Controls

AbstractBackgroundDiagnostic categories within the psychosis spectrum are widely used in clinical practice, however psychosis may occur on a continuum. Therefore, we explored whether the continuous distribution of psychotic symptoms across categories is a function of genetic as well as environmental risk factors, such as polygenic risk scores (PRSs) and cannabis use.MethodsAs part of the EU-GEI study, we genotyped first episode psychosis patients (FEP) and population controls, for whom transdiagnostic dimensions of psychotic symptoms or experiences were generated using item response bi-factor modelling. Linear regression was used, separately in patients and controls, to test the associations between these dimensions and schizophrenia (SZ) PRSs, as well as the combined effect of SZ-PRS and cannabis use on the positive symptom/experience dimensions.ResultsSZ-PRS was associated with negative (B=0.18; 95%CI 0.03 to 0.34) and positive (B=0.19; 95%CI 0.03 to 0.36) symptom dimensions in 617 FEP, and with all the psychotic experience dimensions in 979 controls. The putative effect of SZ-PRS on either symptom or experience dimensions was of a small magnitude. Cannabis use was additionally associated with the positive dimensions both in FEP (B=0.31; 95%CI 0.11 to 0.52) and in controls (B=0.26; 95%CI 0.06 to 0.46), independently from SZ-PRS.ConclusionsWe report two validators to the latent dimensional structure of psychosis. SZ risk variants and cannabis use independently map onto specific dimensions, contributing to variation across the psychosis continuum. Findings support the hypothesis that psychotic experiences have similar biological substrates as clinical disorders.

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CNR2 GENE AND CANNABIS USE INTERPLAY MODULATES MANIPULATIVE ABILITIES IN FIRST-EPISODE OF PSYCHOSIS

10.17579/sepd2021o003 ◽

2021 ◽

Author(s):

Maitane Oscoz Irurozqui ◽

Maria Guardiola-Ripoll ◽

Carmen Almodóvar-Payá ◽

Amalia Guerrero-Pedraza ◽

Edith Pomarol-Clotet ◽

...

Keyword(s):

Cannabinoid Receptor ◽

Clinical Symptoms ◽

Endocannabinoid System ◽

Cognitive Outcomes ◽

Cannabis Use ◽

Psychotic Symptoms ◽

First Episode ◽

The Matrix ◽

General Functioning ◽

Matrix Reasoning

1. Objectives: While endocannabinoid system seems to be involved in processes underlying psychosis, research about Cannabinoid Receptor 2 gene (CNR2) is scarce and inconclusive. Some few reports indicate that CNR2 plays a role in psychiatric conditions, including depression or drug addiction (Onaivi et al., 2009). We aimed to evaluate the role of CNR2 and its interplay with cannabis on cognition and clinical symptoms in patients with a first-episode of psychosis (FEP). 2. Materials and Methods: the sample comprised 50 Caucasian individuals with a FEP (mean age(sd)=26.14(6.55) years, 76% males, 58% cannabis users). There were no differences in age, sex, premorbid IQ and antipsychotic dose between cannabis users (CU) and non-users (CNU). Neuropsychological (premorbid IQ - TAP-E, current IQ - WAIS, memory - WMS, executive function - BADS) and clinical (psychotic symptoms - PANSS, general functioning - GAF) scales were administered. Genetic variability was assessed by genotyping one Single Nucleotide Polymorphism (SNP) in CNR2 gene (rs2501431) (qPCR, TaqMan). 3. Results and conclusions: genotypic frequencies did not differ between cannabis users and non-users. CNR2 was not associated with PANSS scores.; however, it showed a differential effect on the performance IQ (measured by the matrix reasoning test - WAIS), conditional to the cannabis use (beta=0.73, p=0.02),. In particular, cannabis non-users with the AA genotype (23.53%) showed higher scores (mean(sd)=10.25 (1.87)) than those with at least one copy of the G allele (76.47%, mean(sd)=6.05(0.99); while cannabis users showed scores in the opposite direction (AA (42.31%): 8.21(1.09) and GG/GA (57.69%): 10.28(0.92)). Our results align with previous studies reporting the association of the CNR2 gene with psychiatric diseases (Ishiguro et al. 2007; Onaivi et al., 2008) adding evidence on the interplay of this gene with cannabis use on cognitive outcomes in first-episode psychosis. However, evidence is still scant, and further investigation in larger samples is needed.

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