IntroductionApproximately one-third of individuals with schizophrenia will meet the criteria for treatment-resistant schizophrenia (TRS), the majority of whom demonstrate poor pharmacological response early in their course of illness. Clozapine response is higher when used early in the illness trajectory; thus, there is a need to characterize the neurobiological underpinnings of TRS to support early stratification to clozapine. We hypothesized that elevated glutamate in the anterior cingulate cortex (ACC), measured using in vivo magnetic resonance spectroscopy (MRS), would be associated with clozapine eligibility in an early-phase psychosis (EPP) cohort.MethodsCriteria-defined clozapine-eligible (CE) individuals and treatment responders (TR) with non-affective EPP were recruited from the Nova Scotia Early Psychosis Program (within the first 5 years of illness onset). Clinical assessments were completed as well as 3T 1H-MRS to measure glutamate in the bilateral dorsal ACC. 1H-MRS acquisitions were performed using Point RESolved Spectroscopy (TE = 40 ms, TR = 2,000 ms; 128 averages).ResultsForty-six EPP individuals completed the study, with 24 meeting the criteria for clozapine eligibility (mean age = 24) and 22 as treatment responders (mean age = 22). Twenty-six individuals (56.5%) in the total sample were receiving treatment with a long-acting injectable antipsychotic (LAI) medication. The TR group (16 men, 6 women) did not differ from the CE group (19 men, 5 women) in age, years of education, family history of psychosis, or regular nicotine and cannabis use. The CE group had higher PANSS scores, a longer duration of untreated psychosis, and worse social functioning and were taking a higher burden of antipsychotic treatment [chlorpromazine (cpz) equivalencies]. Clinical variables that were significantly different between groups were added to the linear model, and nested model comparisons were used to select the final model for analysis of each metabolite. Glutamate was compared between the groups using a one-way ANOVA, and glutamine was compared using ANCOVA. While ACC glutamate was not found to be significantly different between the groups, glutamine, a precursor for glutamate, was higher in the CE group (M = 4.43, SD = 0.73) relative to the TR group (M = 4.02, SD = 0.64) [F (1, 40) = 5.44, p = 0.02].DiscussionWhile elevated ACC glutamate has been associated with poor response to antipsychotic medications in early psychosis samples, this is the first study to explore the association with clozapine eligibility. Contrary to our hypothesis, ACC glutamate was not higher in the CE group. However, glutamine, a precursor to glutamate, was higher in the CE group, in line with previous studies that have found elevated glutamatergic metabolites to be associated with poor treatment response to antipsychotic medication. Our results support future studies to further characterize the neurobiology of clozapine eligibility in early-phase psychosis to assist in the timely initiation of clozapine to maximize outcomes.

BACKGROUND:Poor engagement with Early Intervention Services (EIS) for first-episode psychosis threatens program effectiveness, yet research often reduces engagement to a binary measure (engaged/disengaged), limiting understanding of those who disengage and re-engage. This study examined demographics, clinical characteristics, and health service utilisation patterns among engaged, intermittently engaged, and disengaged patients of the Nova Scotia Early Psychosis Program (NSEPP). METHODS:A retrospective cohort comprised of 331 individuals enrolled in NSEPP between July 22, 2005, and October 9, 2015, was constructed by linking clinical and administrative datasets. Engagement types (engaged, intermittently engaged, disengaged) were characterised in terms of baseline demographics and clinical factors, along with patterns of health service utilisation before, during, and after program enrollment. Crude and adjusted associations between program engagement and post-program health service utilisation (emergency department (ED) use and mental health-related hospital admissions) were assessed using negative binomial regression models. RESULTS:During program enrollment, the intermittently engaged group had the greatest illness severity (35% spent 30+ days in hospital), and the highest proportion of individuals with at least one ED visit (85%) and one hospital admission (55%). These during-program health service use factors were the strongest predictors of post-program health service use outcomes. CONCLUSIONS:The three engagement types show distinct health service utilisation patterns, which may reflect differences in need, access, or program effectiveness. These results provide evidence that dichotomisation of engagement may mask important heterogeneity. Further characterisation of the engagement continuum to include intermittent engagement may provide insights to reducing barriers and improving access to and uptake of EIS.

BACKGROUND:Recently, there has been a significant rise in potency (% tetrahydrocannabinol (THC)) of cannabis products globally. As such, there is a need for a better understanding of the relationship between cannabis potency and mental health outcomes, especially in a developmentally vulnerable population such as adolescents and young adults. AIMS:The objective of this scoping review was to summarise existing literature investigating the potency of cannabis products as it relates to mental health outcomes in adolescents and young adults aged 14-25. METHOD:Systematic searches of MEDLINE, Embase, CINAHL and PsycINFO were conducted for relevant manuscripts up to October 2025. Following PRISMA-ScR guidelines, retrieved studies were then screened and data extracted by two independent reviewers. RESULTS:Out of 11 225 studies identified by our searches, 71 were included in the review after screening. Compared with low-potency cannabis, our findings suggest that high-potency cannabis is more strongly associated with severe mental health issues, such as cannabis dependence, psychosis and cognitive deficits. CONCLUSIONS:Overall, it was found that high-potency cannabis use (>15% THC) was associated with a great number and magnitude of adverse mental health outcomes. As such, the potency of cannabis products should be measured in future cannabis research that investigates short- and long-term outcomes. Additionally, the potency of cannabis products should be a consideration in any future cannabis regulatory policy discussions.

BACKGROUND:30% of individuals with schizophrenia do not respond to first line dopamine-blocking antipsychotic medications and meet criteria for treatment resistant schizophrenia (TRS). Elevated glutamate levels in the anterior cingulate cortex (ACC) have been found to be associated with poor response to dopamine-blocking antipsychotics in early phase psychosis (EPP). Clozapine is the gold standard treatment for TRS with some evidence suggesting that clozapine may work in part through altering glutamate neurotransmission. However, the exact mechanisms through which clozapine is effective for TRS remain largely unclear and require further investigation. OBJECTIVE:To our knowledge, this is the first study to investigate glutamatergic changes after 6 months of clozapine treatment in patients with EPP. We hypothesized that there would be a decrease in glutamate concentration after 6-months of clozapine treatment. METHOD:Treatment resistant EPP patients were recruited for a larger neuroimaging study; 7 individuals who met criteria for TRS underwent measurement of ACC glutamate prior to starting clozapine, and following clozapine treatment for 6 months. 1H-MRS acquisitions were performed using Point Resolved Spectroscopy in the bilateral dorsal ACC. RESULTS:One case was excluded from imaging analyses due to poor MRS quality (Signal to noise ratio within LCmodel < 12). Paired sample t-test found a non-significant decrease in average glutamate concentration in the ACC 6 months after starting clozapine, (6) = 0.49, p = .647, 95% CI [- 2.72, 4.00]; however, a small effect size was detected (d = 0.34, 95% CI [-0.81, 1.47]). CONCLUSIONS:While there was not a significant change in glutamate in the ACC 6 months after starting clozapine, declining glutamate with a low-moderate effect size is aligned with the hypotheses and may inform future studies. This work suggests that future studies are warranted using a larger sample size. CLINICAL TRIAL NUMBER:Not applicable.

Background The association between cannabis use and suicidality has been established, but details on impacts of legalisation, as well as long-term service use, have had limited attention. Aims To examine if changes are present in suicide presentations with access to legal cannabis. Method This study employed administrative database and medical record reviews to identify two cohorts of patients presenting with suicidal ideation/attempts and cannabis use to emergency departments, for two periods: 17 October 2018 to 30 April 2019, and 17 October 2020 to 30 April 2021. Demographic and clinical outcome data were obtained, and emergency department healthcare usage for 2 years before and 2 years after index encounter were compared, to further understand emergency department presentations for the same complaint. Results Number of emergency department encounters following the index visit and number of emergency department encounters specifically relating to suicidality following the index visit were significantly different between cohorts (t = 2.05, P = 0.042; t = 2.23, P = 0.027, respectively), with the immediate post-cannabis legalisation period demonstrating greater numbers of subsequent emergency department visits for suicidality. Additional associations were found between personality disorders and repeat emergency department visits related to cannabis use. Conclusions There appears to be stability in the patient profile of those presenting to the emergency department with a complaint relating to suicide while reporting cannabis use from the period directly following legalisation in Canada, to a similar time frame 2 years later despite reported increased use of cannabis in the general population over this period. Despite the rising potency and access to legal cannabis, suicide risk remains stable, although concerning.

Cannabis use is widespread and associated with worsened prognosis for young adults with first-episode psychosis (FEP). Few cannabis harm reduction interventions have been evaluated for this population, despite potential to improve outcomes in those not ready for cannabis abstinence/reduction-focused interventions. This study aimed to determine a) the acceptability of a digital harm reduction intervention, the Cannabis Harm-reducing App to Manage Practices Safely (CHAMPS) and b) the feasibility of conducting a trial comparing FEP-specialized early intervention services (EIS)+CHAMPS versus EIS-only with this population. We conducted a multi-site pilot randomized controlled trial comparing both arms in 101 young adults (18 - 35 years old) with FEP using cannabis and attending EIS. Primary outcomes were trial retention rate (i.e., proportion of randomized participants retained at week 6; trial feasibility assessment) and CHAMPS completion rate (i.e., proportion of intervention participants completing four of six modules; CHAMPS acceptability assessment). Trial retention rate above 60 % indicated feasibility and completion rate above 50 % indicated acceptability. Additional outcomes included harm reduction strategy use, motivation to change cannabis behaviors, cannabis-related problems, cannabis use, psychotic symptoms and dependence severity, assessed at baseline, weeks 6, 12 and 18. Trial retention was 82.2 % and completion rate was 58.8 %, suggesting trial feasibility and CHAMPS acceptability. Signals of possible improvement in the intervention group were observed regarding harm reduction strategy use, motivation to change behaviors, cannabis-related problems and cannabis use frequency. This study supports conducting an efficacy trial assessing the potential of CHAMPS in improving outcomes for young adults with psychosis using cannabis.

BACKGROUND:A history of trauma increases risk for excessive and problematic cannabis use, and this relationship may involve conditioned cannabis craving to trauma cues arising through classical and operant conditioning. Alterations in functional connectivity (FC) after trauma reminders within or between brain regions associated with reward processing may potentiate this link; however, the underlying neural mechanisms remain unstudied. METHODS:We recruited cannabis users with trauma histories from February 2021 to August 2022. Participants completed a semi-structured interview about a personally relevant traumatic experience, a typical cannabis use situation unrelated to trauma or stress, and an emotionally neutral situation, with responses informing development of 3-minute audiovisual cues. Using a randomized cross-over design, we presented personalized audio recordings and images of the neutral, cannabis-related, and trauma-related situations to participants in counterbalanced order using a cue reactivity paradigm adapted for the magnetic resonance imaging (MRI) environment. Participants self-reported on subjective cannabis craving and positive and negative affect after each cue presentation. We measured FC between striatal, cortical, and limbic regions via functional MRI during each cue. RESULTS:We included 27 cannabis users with trauma histories (74.1% female, average age 32.2 years, standard deviation 10.5 years). Trauma cues increased cannabis craving and negative affect and decreased positive affect relative to other cues. Cannabis cues increased craving relative to neutral and baseline cues. Trauma cues increased FC within the striatum and between striatal-cortical regions relative to neutral cues and increased striatocortical FC relative to cannabis cues. Cannabis cues increased cortical and corticolimbic FC relative to trauma cues and increased striatocortical FC relative to neutral cues. LIMITATIONS:The sample was small in size and not formed exclusively of participants with diagnoses of posttraumatic stress disorder or cannabis use disorder. CONCLUSION:Findings suggested potential neural mechanisms underlying the link between trauma and cannabis use. Trauma- and cannabis-related cues may potentiate cannabis craving through altered reward circuit FC.

Substance misuse significantly impacts recovery during early phase psychosis (EPP). However, effective psychotherapeutic interventions for substance misuse in EPP patients are limited. Cognitive remediation offers a novel approach by targeting mechanisms underlying substance use, including cognitive control and emotional regulation. This pilot study aimed to explore the feasibility of using a modified Cognitive Enhancement Therapy (CET) intervention in young adults with EPP, examining its effects on problematic alcohol use. This intervention, which focuses on remediation of neurocognitive and social cognitive deficits, was adapted with a reduced timeframe (6 months) and delivered via a virtual platform with the intent to improve retention. Participants who received CET saw improvements in verbal learning and memory, along with reductions in negative psychotic symptoms. Although the small sample size precluded statistical analyses, a notable reduction (50 %) in alcohol use, or cessation, was seen in 6 out of 7 participants with 3 individuals notably reaching abstinence by the trial end. Overall alcohol use was reduced by 35 %. Additionally, 3 participants with co-occurring cannabis use had significant reduction in cannabis risk scores (60 %) over the course of the trial. Feedback from the participants suggests CET's focus on emotional regulation, social confidence, and functional recovery contributed to their reduction in alcohol dependence. These promising outcomes highlight the need for further research to explore the potential benefits of cognitive remediation treatments for addressing substance misuse in EPP. This study was registered at clinicaltrials.gov under #NCT05365347.

Background:Patients treated in early intervention for psychosis programs have better treatment outcomes and higher rates of long-acting injection (LAI) antipsychotic medication utilization (20%-50%) versus treatment as usual. These programs usually serve patients for 2-3 years, then most patients are discharged to other mental health services and studies of patients with longer-standing schizophrenia suggest switching to oral medications may be common. However, following patients post-discharge is complicated by the challenges of migrated patient records across clinical services and providers. Objectives:To examine whether LAI use continues after discharge from an early intervention service for psychosis. Design:This study was a retrospective cohort study examining the effects of continuation or discontinuation of LAI therapy in individuals who have completed treatment in an early intervention service (EIS) for psychosis. Methods:A retrospective cohort was created from a group of individuals discharged from EIS for psychosis over a 3-year period from January 1, 2016 to December 31, 2018 and followed for mental health outcomes and antipsychotic medications prescribed for a subsequent 2-year period at discharge, 6, 12, 18, and 24 months post-discharge. Results:Of 85 subjects discharged from three sites in three different provinces in Canada for whom full follow-up could be recorded, 60 subjects remained on LAI medications after 24 months (71%). The average age of the cohort was 22 years (SD 4.7) at admission to an EIS. At discharge, the most commonly used LAI was aripiprazole, and most subjects were maintained on the same formulation at 24 months, if still on LAI. Reasons for discontinuation were predominantly patient preference. Significant differences in clinical outcomes, measured through reduced rehospitalization were seen for those who remained on LAI as compared to those who did not. Conclusion:LAI adherence is still strong 24 months after discharge from an EIS for psychosis.

IntroductionAdolescence and young adulthood are simultaneously periods of significant brain development and the ages in which people often initiate cannabis use. This has led to significant interest in researching the effects that cannabis use in this period might have on the brains of users. This scoping review aims to summarize existing neuroimaging research on the effect of cannabis use in adolescence and/or young adulthood (ages 14-25) on brain structure, function, and metabolite concentrations.MethodsFollowing scoping review methodology, databases containing neuroimaging studies assessing the effects of cannabis use between the ages of 14 and 25 on brain structure, function, and metabolite concentrations were searched.ResultsOur search yielded 3901 sources, of which 99 met inclusion criteria. The majority of included papers (84/99) found differences in the brain structure, function, and/or metabolite concentrations of adolescent/young adult cannabis users compared to non-using controls. Fewer studies explicitly assessed sex/gender differences, with 5 finding that sex/gender influenced the effect of cannabis use on the brain.ConclusionBased on the findings of this review, there is considerable evidence to suggest that cannabis use in adolescence/young adulthood causes changes in the brains of users, however, the low quality of relevant research and scarcity of long term follow up studies, in addition to the heterogeneity of the existing research suggests that more work needs to be done to understand this relationship.

Abstract Background Several adversity-focused treatment trials have reported improvements to adversity sequelae (e.g., PTSD symptoms) and decreases in psychotic symptoms among individuals with psychotic disorders. Yet, no trials have examined the impact of adversity-focused treatment on substance use or examined the outcomes among an early phase psychosis population. These gaps in both the research literature and clinical practice have resulted in less knowledge about the outcomes of adversity-focused treatment at this stage of illness, including the impact on substance use. Methods The outcomes of an adapted prolonged exposure protocol (PE+) among an early phase psychosis population were examined using a multiple-baseline design. Nineteen adults with a psychotic disorder, current substance misuse, and a history of adversity were recruited from an early psychosis program. Participants were randomized to treatment start time and participated in a 15-session course of PE + therapy. Ten assessments were completed focusing on primary outcomes (i.e., adversity sequelae, negative psychotic symptoms, substance misuse) and secondary outcomes (i.e., functioning, hopelessness, experiential avoidance). The Reliable Change Index (RCI) was used to establish whether there were clinically significant changes to primary or secondary outcomes. Results Half or more of treatment completers experienced clinically significant changes to most domains of adversity sequelae, no participants experienced improvements in negative psychotic symptoms, and substance misuse increased for several participants. In terms of secondary outcomes, functioning and experiential avoidance were improved for a number of participants, while hopelessness decreased for only one participant. Participants reported high satisfaction with the PE + treatment, and exposure and coping skills were rated as the most helpful elements of treatment. Conclusions Reductions in adversity sequelae were observed following PE + treatment, suggesting that adversity-focused treatment may be beneficial for an early psychosis population. Yet, few positive changes to psychotic symptoms or substance use were observed. Further integrating treatment strategies for psychosis and substance use into PE + may be required to effectively treat the links between psychosis, adversity sequelae, and substance use. Future studies should make efforts to integrate substance use strategies into adversity treatment trials for people with psychotic disorders. Trial registration Clinicaltrials.gov, NCT04546178; registration posted 11/09/2020, https://clinicaltrials.gov/ct2/show/NCT04546178?term=NCT04546178&draw=2&rank=1.

This study examined the relationship between terminal referral source and subsequent urgent health service use in a Canadian early intervention service (EIS) for psychosis. Administrative health record data of emergency and inpatient mental health service use over a 2-year follow up from entry to EIS were retrospectively analyzed (n = 515). Negative binomial regression models were used to assess for the relationship between referral source and care outcomes. Compared to those referred from primary care services, the rate of urgent health care use was significantly greater for individuals referred to early intervention services from urgent care services while accounting for social and occupational functioning and psychotic symptom severity. Findings suggest that those referred from urgent services may be at an increased risk for subsequent urgent health care use while attending EIS for psychosis. Further research examining this relationship while incorporating additional relevant predictors is needed.

AIM:Most young adults experiencing psychosis enter early intervention services (EIS) via inpatient and emergency departments. These experiences are suggested to negatively impact their views of treatment and engagement in EIS. However, limited research has examined the impact of young adults' prior help-seeking experiences on these outcomes. The present study aimed to explore how young adults engaged in EIS have experienced initial help-seeking and make sense of these experiences in the context of their current treatment. METHODS:Using an interpretative phenomenological analysis approach, semi-structured interviews were conducted with 12 young adults (mean age = 24.83) within their first 3-12 months of treatment in EIS. Interviews aimed to examine their experiences of help-seeking and referral to EIS as well as the impact of these experiences on their subsequent perception of, and engagement with EIS. RESULTS:3 superordinate themes emerged: (1) Navigating the Maze of Healthcare (2) Dignity and (3) Impact of Help-Seeking and Referral Experiences. Participants with referral pathways involving urgent care services described more adversity during their referral pathway and tended to describe help-seeking experiences as contributing to negative views towards EIS and diminished engagement in treatment. CONCLUSIONS:The impact of early negative experiences with healthcare on views towards EIS and engagement is evident in participants' accounts. Sense making was further contextualized by participants' illness insight, degree of recovery, and social support throughout experiences. Emergent themes highlight the need for psychiatric services to emphasize service users' dignity and for EIS to provide opportunities for patients to process past negative mental healthcare experiences to strengthen engagement.

Psychotic-like experiences (PLEs) are common in the general population. Child and adolescent PLEs are the most prevalent and linked with future psychotic disorders. Significant heterogeneity in PLE assessment has obscured its clinical utility to identify psychosis-prone trajectories and improve clinical outcomes. This meta-analysis aimed to assess i) PLE prevalence in children and adolescents and ii) their relationship with subsequent psychotic disorder while exploring sources of heterogeneity. PubMed, Embase, PsycINFO, and CINAHL databases were searched in August 2023 for population-based longitudinal studies that assessed child or adolescent PLEs and early adulthood psychotic outcomes. Six studies were included (n = 16,560), showing a pooled PLE prevalence of 17.3 %. Child and adolescent PLEs were associated with an increased risk of psychotic disorder in early adulthood (unadjusted OR = 3.80, 95 % CI: 2.31-6.26), with a population attributable fraction of 32.6 %. Significant heterogeneity in the strength of this relationship (I2 = 70 %, p = .01) was related to assessment type (self-report vs. interview). This review contends that interview-based PLE assessments could more accurately identify children or adolescents on a path towards psychosis and are better suited for psychotic risk identification. Further research is needed to elucidate interactions between PLEs and other psychotic risk factors.

Using electroencephalography (EEG) to examine the simple mismatch negativity (MMN), a marker of auditory cortex function, has been of great interest in the exploration of biomarkers for psychotic illness. Despite many studies reporting MMN deficits in chronic schizophrenia, there are inconsistent reports of MMN reductions in the early phases of psychotic illness, suggesting the MMN elicited by traditional paradigms may not be a sensitive enough measure of vulnerability to be used as a biomarker. Recently, a more computationally complex measure of auditory cortex function (the complex mismatch negativity; cMMN) has been hypothesized to provide a more sensitive marker of illness vulnerability. The current study employed a novel dual rule paradigm, in which two pattern rules are established and violated, to examine the cMMN in 14 individuals with early phase psychosis (EPP, < 5 years illness) and 15 healthy controls (HC). Relationships between cMMN waveforms, symptom severity, and measures of functioning were explored. We found reductions of cMMN amplitudes at the site of maximal amplitude in EPP ( p = .017) with large effect sizes ( Hedges’ g = 0.96). This study is an early step in the exploration of the cMMN as a biomarker for psychosis. Our results provide evidence that the dual rule cMMN paradigm shows promise as a method for cMMN elicitation that captures more subtle neurofunctional changes in the early stages of illness.

High levels of cannabis use have been established as a risk factor for the development of psychotic disorders and may exacerbate existing mental illness. Despite extensive research on the adverse effects of cannabis, less attention has been given to a concerning phenomenon: the onset and exacerbation of acute psychotic symptoms following abrupt cessation of cannabis use. This case series presents three individuals who developed their first episode of psychosis shortly after discontinuing heavy cannabis use (several grams daily). These cases underscore the potential link between cannabis withdrawal and the emergence or exacerbation of psychotic symptoms which may led to a psychotic episode, highlighting the need for greater public health awareness of safe cannabis use practices. The discussion explores potential mechanisms such as dysregulation of the endocannabinoid and dopamine systems following long-term cannabis use, which may predispose individuals to psychosis during withdrawal. The findings advocate for safer cannabis discontinuation guidelines, suggesting gradual reduction in cannabis use and potency of product consumed as preventive measures. Further research is essential to explore predictive risk factors and refine approaches to mitigate the risk of psychosis associated with cannabis withdrawal in vulnerable populations.

The use of long-acting injectable (LAI) antipsychotic drugs for psychotic disorders in Canada has been historically low compared to other jurisdictions despite advantages of LAIs in improving medication adherence and preventing relapse. In response, treatment recommendations were developed in 2013 by the Canadian Consortium for Early Intervention in Psychosis and other Canadian provincial expert groups. The impact of these guidelines needed to be assessed. To document practices in LAI use in early intervention services (EIS) for psychosis, Canadian EIS were surveyed in 2016 (n = 18) and 2020 (n = 12). Trends and descriptive information were examined using repeated cross-sectional survey data. Eight EIS responded to surveys at both time points allowing for longitudinal comparisons. Outcomes of interest included i) LAI use frequency, ii) timing of LAI starts, and iii) factors influencing LAI use. Cross-sectional analysis identified a significant increase in overall LAI usage (24.7% in 2016; 35.1% in 2020). Longitudinal analysis indicated that patients in the second program year saw the greatest increase in LAI use between 2016 and 2020 (25.6% vs. 36.1%), especially among patients under community treatment orders (65.5% vs. 81.5%). Results support increases in LAI use over time, accessibility, awareness, and increasing comfortability among Canadian clinicians.

We have previously reviewed the types and numbers of cannabis-associated adverse events that have mental health presentations that are encountered in the Emergency Department. A particular challenge in examining these events is disentangling cannabis use adverse events from adverse events associated with use of multiple recreational substances. Since that review was published, cannabis legalization for recreational use has greatly expanded world-wide and with these changes in the legal climate has come clearer information around the frequency of adverse events seen in the Emergency Department. However, as we examined the current state of the literature, we also examined some of research designs and the biases that may be impacting the validity of the data in this field. The biases both of clinicians and researchers as well as research approaches to studying these events may be impacting our ability to assess the interaction between cannabis and mental health. For example, many of the studies performed examining cannabis-related admissions to the Emergency Department were administrative studies that relied on front line clinicians to identify and attribute that cannabis use was associated with any particular admission. This narrative review provides an overview on what we currently know about mental health adverse events in the Emergency Department with a focus on the mental health impacts both for those with and without a history of mental illness. The evidence that cannabis use can adversely impact genders and sexes differently is also discussed. This review outlines what the most common adverse events related to mental health with cannabis use are; as well as noting the most concerning but much rarer events that have been reported. Additionally, this review suggests a framework for critical evaluation of this field of study going forward.

Background: Most young adults experiencing psychosis enter early intervention services for psychosis (EIS) via inpatient services and emergency departments. Referral in this manner is believed to increase young adults’ risk for adverse outcomes while in EIS such as diminished trust and engagement in services. However, little research has empirically examined the impact of young adults’ referral and help-seeking experiences on their subsequent views towards EIS and engagement to services. Methods: This qualitative study involved semi-structured interviews with 12 young adults (mean age = 24.83) within 3-12 months following acceptance to an EIS. Interviews aimed to examine their experiences of help-seeking and referral to EIS as well as the impact of these experiences on their subsequent perception of, and engagement with EIS. Data were analyzed using the Interpretative Phenomenological Analysis approach. Results: 3 superordinate themes emerged: (1) Navigating the Maze of Healthcare (2) Dignity and (3) Impact of Events . Participants with referral pathways involving urgent care services, particularly through involuntary hospitalization, described more adversity during their referral pathway and were more likely to describe help-seeking experiences as contributing to negative views towards EIS and diminished engagement in treatment. Conclusions: The impact of early negative experiences with healthcare on views towards EIS and engagement is evident in participants’ accounts. Sense making was further contextualized by participants’ illness insight, degree of recovery, and social support throughout experiences. Emergent themes highlight the need for psychiatric services to emphasize service users’ dignity and for EIS to provide opportunities for patients to process past negative healthcare experiences to strengthen engagement.