Hearing impairment and psychosis revisited

The previously reported but still poorly investigated link between deafness or hearing impairment (DHI) and the onset of positive psychotic experiences was investigated prospectively in a general population sample. Of the 109 DHI subjects at baseline, 11 (10.1%) displayed psychotic experiences at T(2) versus 137 (2.9%) of the non-DHI subjects (OR=3.8, 95% CI: 2.0, 7.2). This effect size was only slightly attenuated after adjustment for baseline psychotic experiences (OR=3.2, 95% CI: 1.6, 6.5) and after adjustment for T(0) psychotic experiences and a range of other confounders (OR=3.0, 95% CI: 1.4, 6.2) These results confirm previous findings of an association between hearing impairments and psychosis and show that this association can also be found prospectively in a nonclinical population.     

Daily Use,Especially of High-Potency Cannabis,Drives the Earlier Onset of Psychosis in Cannabis Users

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11–1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.Key words: psychotic disorders, age of onset, gender, cannabis, survival plots, drug use, high-potency cannabis     

Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986

Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036–0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96–1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07–1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis.     

COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life

Objective: A functional polymorphism in the catechol‐o‐methyltransferase gene (COMT Val¹⁵⁸Met) may moderate the psychosis‐inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. Method: The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). Results: Carriers of the COMT Val¹⁵⁸Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. Conclusion: The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val¹⁵⁸Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.     

Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad

Objective: Cannabis use increases the risk for psychosis, but psychotogenic effects of cannabis may be restricted to exposure during early adolescence. Method: Four hundred and seventy‐two participants (aged 12–23 years), randomly selected from the general population in Trinidad, completed questionnaires on past and current cannabis use and psychotic symptoms (using the Community Assessment of Psychic Experiences). Results: Cannabis use increased the risk of experiencing psychotic symptoms and this effect was conditional on early exposure, defined around the mean age of onset of cannabis use. Thus, exposure before but not after the age of 14 years predicted psychotic symptoms (respectively β: 0.71, 95% CI 0.22; 1.19, P = 0.004 and β: ?0.11, 95% CI ?0.57; 0.36, P = 0.66). The developmental effect of cannabis use was independent of use of other drugs or current use of cannabis. Conclusion: Early adolescence may be a critical period with regard to the psychotogenic effect of cannabis across geographical settings and ethnic groups.     

Cannabis and First-Episode Psychosis: Different Long-term Outcomes Depending on Continued or Discontinued Use

Objective: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. Methods: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). Results: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI] = 0.65 to 1.86) for functional outcome and −0.72 (95% CI = −1.27 to −0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. Conclusion: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.     

Cannabis use and dimensions of psychosis in a nonclinical population of female subjects

OBJECTIVE: The aim of the present study was to explore the pattern of associations between cannabis use and dimensions of psychosis in a nonclinical population of female subjects. METHOD: The Community Assessment of Psychic Experiences (CAPE), a 42-item self-report questionnaire that evolved from the Peters et al. Delusions Inventory [Schizophr. Bull. 25 (1999) 553], was used to measure dimensions of psychosis in a sample of undergraduate female students (n=571). The participants were also asked to complete a self-report questionnaire collecting information on substance use. RESULTS: Three correlated dimensions of positive, negative and depressive experiences were identified using principal components factor analysis. Frequency of cannabis use was independently associated with the intensity of both positive and negative psychotic experiences. No significant association was found between cannabis use and the depressive dimension, or between alcohol use and any of the three positive, negative and depressive dimensions. CONCLUSION: This cross-sectional study supports the hypothesis that exposure to cannabis may induce the emergence of positive psychotic symptoms in subjects without clinical psychosis, and additionally suggests that cannabis users exhibit greater levels of negative symptoms. Prospective studies are required to explore the direction of causality and the impact of cannabis on the course of psychotic experiences in subjects from the general population.     

Interplay Between Childhood Physical Abuse and Familial Risk in the Onset of Psychotic Disorders

Background: Childhood abuse is considered one of the main environmental risk factors for the development of psychotic symptoms and disorders. However, this association could be due to genetic factors influencing exposure to such risky environments or increasing sensitivity to the detrimental impact of abuse. Therefore, using a large epidemiological case-control sample, we explored the interplay between a specific form of childhood abuse and family psychiatric history (a proxy for genetic risk) in the onset of psychosis. Methods: Data were available on 172 first presentation psychosis cases and 246 geographically matched controls from the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study. Information on childhood abuse was obtained retrospectively using the Childhood Experience of Care and Abuse Questionnaire and occurrence of psychotic and affective disorders in first degree relatives with the Family Interview for Genetic Studies. Results: Parental psychosis was more common among psychosis cases than unaffected controls (adjusted OR = 5.96, 95% CI: 2.09–17.01, P = .001). Parental psychosis was also associated with physical abuse from mothers in both cases (OR = 3.64, 95% CI: 1.06–12.51, P = .040) and controls (OR = 10.93, 95% CI: 1.03–115.90, P = .047), indicative of a gene-environment correlation. Nevertheless, adjusting for parental psychosis did not measurably impact on the abuse-psychosis association (adjusted OR = 3.31, 95% CI: 1.22–8.95, P = .018). No interactions were found between familial liability and maternal physical abuse in determining psychosis caseness. Conclusions: This study found no evidence that familial risk accounts for associations between childhood physical abuse and psychotic disorder nor that it substantially increases the odds of psychosis among individuals reporting abuse.Key words: family history, gene-environment correlation, gene-environment interaction, liability, schizophrenia, trauma     

Fewer neurological soft signs among first episode psychosis patients with heavy cannabis use

BACKGROUND: Although neurological soft signs (NSS) have been consistently associated with schizophrenia and a variety of risk factors, few studies have focused on the association between NSS and environmental factors such as cannabis use, particularly in patients with first episode psychosis. METHODS: We administered the Neurological Evaluation Scale (NES) to 92 patients during their first episode of functional psychosis. Psychopathology was assessed with the Positive And Negative Syndrome Scale (PANSS) and the family history of psychotic disorder was established on the basis of the Family Interview for Genetic Studies (FIGS). We also assessed lifetime cannabis and cocaine use utilizing that specific section of the Composite International Diagnostic Interview. The outcome variable was the presence of high NSS, defined by a score above the median split of the NES score (>21). RESULTS: Most patients (80/92, 87%) presented a non-affective psychosis. The presence of high NSS showed a significant independent association with not having been a heavy cannabis user (OR=8.3; 95% CI, 2.4-33.3), family history of psychosis (OR=4.3; 95% CI, 1.2-14.9), male sex (OR=4.0; 95% CI, 1.2-14.0), lower score in verbal fluency and higher score in negative symptoms (both p<0.01). CONCLUSION: Our cross-sectional results support the hypothesis that potentially different pathways associated with the emergence of first episode psychosis may exist, including neurological premorbid alteration and environmental cannabis abuse.     

Sex differences in symptoms of psychosis in a non-selected,general population sample

BACKGROUND: Little is known about sex differences in psychosis beyond the borders of clinical disorder. METHODS: A general population sample of 7,076 subjects was assessed using the Composite International Diagnostic Interview, in order to explore sex differences in the prevalence of any positive and negative symptoms of psychosis, and to examine to what degree any differences could be explained by differences in level of affective symptoms. RESULTS: Male sex was associated with higher prevalence of negative symptoms (OR = 1.6, 95% CI = 1.0, 2.5), independent of differences in affective symptoms and presence of DSM-III-R psychotic disorder. Women had higher rates of positive psychotic experiences (OR = 0.8, 95% CI = 0.7, 0.9), but this difference disappeared after adjustment for depressive symptoms (adjusted OR = 1.2, 95% CI = 0.9, 1.5). CONCLUSION: The sex differences in psychopathology that are seen in schizophrenia are expressed beyond the clinical phenotype, suggesting sex-dependent continuous and normal variation of several psychosis dimensions. The higher rates of positive psychotic experiences seen in women may be secondary to differences in the rate of affective symptoms.     

Influence of cannabis use on incidence of psychosis in people at clinical high risk

Aims

Evidence for case–control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome.

Methods

Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale.

Results

During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome.

Conclusions

These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.     

Do cognitive schema mediate the association between childhood trauma and being at ultra-high risk for psychosis?

Exposure to childhood trauma has been associated with psychotic symptoms, being at ultra-high risk for psychosis (UHR), and psychotic disorders such as schizophrenia. Negative self-beliefs have been shown to partially mediate the relationship between childhood trauma and paranoia and have been shown to be characteristic of patients with psychosis. However, whether the association between childhood trauma and being at high risk of developing psychosis (e.g., UHR) and paranoia symptoms is mediated by altered cognitive schema is unknown and warrants investigation to inform preventive interventions. Data was collected on 30 UHR patients from Outreach and Support in South London about exposure to childhood trauma, cognitive schema, paranoia and cannabis use. Relative to healthy controls (n = 38), UHR patients were significantly more likely to report exposure to various types of childhood trauma (emotional and sexual abuse, and emotional and physical neglect), had more negative schema and less positive schema about themselves and others, and were more likely to use cannabis more than once a month. Emotional neglect was found to be significantly associated with UHR status even after controlling for the effects of previous exposure to cannabis use (b = 0.262, 95% CI: 0.115–0.408), and this association was partially mediated by negative self-schema (b = 0.045, 95% CI: 0.004–0.159). Similarly, emotional neglect was significantly associated with paranoia (b = 1.354, 95% CI: 0.246-2.462), and this association was partially mediated by negative self-schema (b = 0.988, 95% CI: 0.323-1.895). These findings provide preliminary evidence about the cognitive mechanisms that may underlie the association between childhood trauma and later risk for psychosis.     

Early course of schizophrenia in a representative Dutch incidence cohort

PURPOSE: To describe the early course of psychotic disorders in general and to examine whether certain variables can predict the early course of schizophrenic disorders (DSM-IV: schizophrenia, schizophreniform or schizoaffective disorder). SUBJECTS AND METHOD: Follow-up and re-diagnosis of a highly representative Dutch incidence cohort (N=181), thirty months after first contact with a physician for a psychotic disorder. Poor course was defined as a continuous psychotic illness or a score of less than 39 on the Global Assessment of Functioning scale. RESULTS: The follow-up rate was 92%. 125 Subjects were diagnosed with a schizophrenic disorder. Poor course was present in 70 of these subjects (56%). Univariable analysis showed that male sex, heavy cannabis use during the follow-up period (sometimes or often more than one joint a day) and long duration of dysfunctioning before psychosis onset (>1 month) were predictors of poor course, while age at onset, ethnicity, socioeconomic status and duration of untreated psychosis (trend, p=0.08) were not. The effect of cannabis was confounded by sex. Multivariable analysis showed that male sex was the sole significant and independent predictor of poor course and explained 13% of the variation. The odds ratio for males, adjusted for duration of pre-psychotic dysfunctioning and cannabis use during the follow-up period, was 3.0 (95% CI, 1.0-8.9). STRENGTHS AND LIMITATIONS: This is the first study to examine the influence of cannabis in an epidemiological, highly representative sample. A limitation was the sample size. CONCLUSION: Male sex is an independent risk factor for an unfavorable early course in schizophrenia.     

Cannabis use and depression: a longitudinal study of a national cohort of Swedish conscripts

ABSTRACT: BACKGROUND: While there is increasing evidence on the association between cannabis use and psychotic outcomes, it is still unclear whether this also applies to depression. We aim to assess whether risk of depression and other affective outcomes is increased among cannabis users. METHODS: A cohort study of 45 087 Swedish men with data on cannabis use at ages 18[EN DASH]20. Diagnoses of unipolar disorder, bipolar disorder, affective psychosis and schizoaffective disorder were identified from inpatient care records over a 35-year follow-up period. Cox proportional hazard modeling was used to assess the hazard ratio (HR) of developing these disorders in relation to cannabis exposure. RESULTS: Only subjects with the highest level of cannabis use had an increased crude hazard ratio for depression (HR 1.5, 95% confidence interval (CI), 1.0-2.2), but the association disappeared after adjustment for confounders. There was a strong graded association between cannabis use and schizoaffective disorder, even after control for confounders, although the numbers were small (HR 7.4, 95% CI, 1.0-54.3). CONCLUSION: We did not find evidence for an increased risk of depression among those who used cannabis. Our finding of an increased risk of schizoaffective disorder is consistent with previous findings on the relation between cannabis use and psychosis.     

Self-report of family functioning and risk for psychotic disorders in male adolescents with behavioural disturbances

Objective: Previous studies indicate that a poor family environment might affect vulnerability for the later manifestation of psychotic illness. The current study aims to examine family functioning prior to the onset of psychosis. Method: Subjects were 42 948, 17‐year old males with behavioural disturbances who were asked about the functioning of their family by the Israeli Draft Board. Data on later psychiatric hospitalizations were obtained from a National Psychiatric Hospitalization Registry. Results: Poorer self‐reported family functioning was associated with greater risk for later hospitalization for psychosis [adjusted hazard ratio (HR) = 1.16, 95% CI = 1.05–1.27], with a trend in the same direction for schizophrenia (adjusted HR = 1.1, 95% CI = 0.98–1.24). Conclusion: In male adolescents with behavioural disturbances, perceived poorer family functioning is associated with increased risk for non‐affective psychotic disorders and schizophrenia. These data do not enable us to determine if perceived familial dysfunction increases vulnerability for psychosis, if premorbid behavioural abnormalities disrupt family life, or neither.     

Cannabis use is not associated with the development of psychosis in an 'ultra' high-risk group

BACKGROUND: The association between cannabis use and the development of a first psychotic episode was studied in a group of 100 young people identified as being at very high risk for the onset of psychosis. METHOD: The 'ultra' high risk cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-two per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of cannabis use by participants in the year prior to enrollment in the study was assessed at intake. RESULTS: Cannabis use or dependence in the year prior to recruitment to this study was not associated with a heightened risk of developing psychosis over the following 12-month period and therefore did not appear to contribute to the onset of a psychotic disorder. CONCLUSION: The results of this study suggest that cannabis use may not play an integral role in the development of psychosis in a high-risk group. While this study does not support a role for cannabis in the development of first-episode psychosis, we cannot conclude that cannabis use should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study (the low level of cannabis use in the current sample, the lack of monitoring of cannabis use after intake) suggest that it may be premature to dismiss cannabis use as a risk factor for the development of psychosis and further research is urged in this area.     

Cognitive Behavioral Therapy for Prodromal Stage of Psychosis—Outcomes for Transition,Functioning, Distress,and Quality of Life: A Systematic Review and Meta-analysis

ObjectiveThis study aimed to provide insight into the efficacy of cognitive-behavioral therapy for psychosis (CBTp) in patients with “clinical high risk of psychosis (CHR-P)”.MethodsMajor scientific databases were searched up to April 17, 2020. Randomized controlled trials in CHR-P individuals, comparing CBTp with needs-based interventions (NBI, including treatment as usual or nonspecific control treatment) were included, following PRISMA guidelines. The primary outcome (efficacy) was transition to psychosis by 6 months, 12 months, 24 months, and over 24 months. Secondary outcomes were change in attenuated psychotic symptoms, depression, distress, improvements in functioning, and quality of life.ResultsTen randomized controlled studies met inclusion criteria. The comparisons included 1128 participants. CBTp was significantly more efficacious in reducing rate of transition to psychosis by 6 months (after post-hoc sensitivity analysis) (relative risk [RR] = 0.44, 95% confidence interval [CI]: 0.26, 0.73), 12 months (RR = 0.44, 95% CI: 0.30, 0.64), 12 months (RR = 0.46, 95%CI: 0.30, 0.69), and over 24 months (RR = 0.58, 95% CI: 0.35, 0.95) after treatment, compared with those receiving NBI. CBTp was also associated with more reduced attenuated psychotic symptoms by 12 months (SMD = −0.17, 95% CI: −0.33, −0.02) and by 24 months (SMD = −0.24, 95% CI: −0.43, −0.06). No beneficial effects on functioning, depression, quality of life, or distress were observed favoring CBTp.ConclusionsCBTp is effective in reducing both psychosis transition rates and attenuated psychotic symptoms for the prodromal stage of psychosis. It is a promising intervention at the preventative stage.     

Does Change in Cannabis Use in Established Psychosis Affect Clinical Outcome?

Background: Cannabis use has been identified as a potent predictor of the earlier onset of psychosis, but meta-analysis has not indicated that it has a clear effect in established psychosis. Aim: To assess the association between cannabis and outcomes, including whether change in cannabis use affects symptoms and functioning, in a large sample of people with established nonaffective psychosis and comorbid substance misuse. Methods: One hundred and sixty participants whose substance use included cannabis were compared with other substance users (n = 167) on baseline demographic, clinical, and substance use variables. The cannabis using subgroup was examined prospectively with repeated measures of substance use and psychopathology at baseline, 12 months, and 24 months. We used generalized estimating equation models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes. Results: Cannabis users showed cross-sectional differences from other substances users but not in terms of positive symptoms. Second, cannabis dose was not associated with subsequent severity of positive symptoms and change in cannabis dose did not predict change in positive symptom severity, even when patients became abstinent. However, greater cannabis exposure was associated with worse functioning, albeit with a small effect size. Conclusions: We did not find evidence of an association between cannabis dose and psychotic symptoms, although greater cannabis dose was associated with worse psychosocial functioning, albeit with small effect size. It would seem that within this population, not everyone will demonstrate durable symptomatic improvements from reducing cannabis.     

Cannabis Use and Prospective Long-Term Association with Anxiety: A Systematic Review and Meta-Analysis of Longitudinal Studies: Usage du cannabis et association prospective à long terme avec l’anxiété: une revue systématique et une méta-analyse d’études longitudinales

Objectives:Cannabis use is proposed as a risk factor for psychosis and is associated with depressive disorders. However, the relationship between recreational cannabis use and its longitudinal implications on anxiety conditions is less studied. The aim of this investigation is to systematically evaluate published literature and perform a meta-analysis of the data.Methods:A systematic search was performed of MEDLINE, Embase, and PsychINFO from inception to May 31, 2020, in addition to a hand search. Longitudinal studies that evaluated the relationship of cannabis use and development of anxiety were included. Where applicable, adjusted odds ratios (ORs) were extracted, pooled, and evaluated using random-effects meta-analysis.Results:After screening of unique abstracts (n = 6835), the final evaluation included 24 studies, of which 10 reported ORs that were analyzed quantitatively. Cannabis use was significantly associated with increased odds of developing any anxiety conditions (OR = 1.25; 95% CI, 1.01 to 1.54). Cannabis use was not significantly associated with developing generalized anxiety disorder, panic disorder, or social anxiety disorder. Review of studies not reporting OR revealed mixed results but are suggestive of a link between cannabis use and increased rates/severity of anxiety.Conclusions:Published evidence suggests that cannabis use is likely associated with increased risk of anxiety in the long term but variability of study designs precludes declaration of a causal relationship. Awareness of this association is of relevance for both clinical practice and mental health policy implementation.