Referral pathways to early intervention services for psychosis and their influence on perceptions of care: An interpretive phenomenological analysis.

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.

The role of referral pathway to early intervention services for psychosis on 2-year inpatient and emergency service use.

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.

Short communication: Prevalence of long-acting injectable antipsychotic use in Canadian early intervention services for psychosis.

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.

Mental health adverse events with cannabis use diagnosed in the Emergency Department: what are we finding now and are our findings accurate?

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.

A multiple baseline trial of adapted prolonged exposure psychotherapy for individuals with early phase psychosis, comorbid substance misuse, and a history of adversity: A study protocol.

Background: Adversity is prevalent among people with psychotic disorders, especially those within the first 5 years of a psychotic disorder, called early phase psychosis. Although adversity can lead to many negative outcomes (e.g., posttraumatic stress symptoms), very few treatments for adversity-related sequelae have been tested with individuals with psychotic disorders, and even fewer studies have specifically tested interventions for people in early phase psychosis. Furthermore, people who misuse substances are commonly excluded from adversity treatment trials, which is problematic given that individuals with early phase psychosis have high rates of substance misuse. For the first time, this trial will examine the outcomes of an adapted 15-session prolonged exposure protocol (i.e., PE+) to observe whether reductions in adversity-related psychopathology occurs among people with early phase psychosis and comorbid substance misuse. Methods: This study will use a multiple-baseline design with randomization of participants to treatment start time. Participants will complete baseline appointments prior to therapy, engage in assessments between each of the five therapy modules, and complete a series of follow-up appointments 2 months after the completion of therapy. Primary hypothesized outcomes include clinically significant reductions in (1) negative psychotic symptoms measured using the Positive and Negative Syndrome Scale, (2) adversity-related sequelae measured using the Trauma Symptom Checklist-40, and (3) substance use frequency and overall risk score measured with the Alcohol, Smoking, and Substance Involvement Screening Test. We also anticipate that clinically significant reductions in hopelessness and experiential avoidance, measured with the Beck Hopelessness Scale and Brief Experiential Avoidance Questionnaire, the theorized mechanisms of change of PE+, will also be observed. A secondary outcome is a hypothesized improvement in functioning, measured using the Clinical Global Impression and Social and Occupational Functioning Assessment scales. Discussion: The results of this treatment trial will contribute to the advancement of treatment research for individuals in early phase psychosis who have current substance misuse and a history of adversity, and the findings may provide evidence supporting the use of hopelessness and experiential avoidance as mechanisms of change for this treatment. Clinical trial registration: Clinicaltrials.gov, NCT04546178; registered August 28, 2020, https://clinicaltrials.gov/ct2/show/NCT04546178?term=NCT04546178&draw=2&rank=1.

Interaction of sex and cannabis in adult in vivo brain imaging studies: A systematic review.

Cannabis has been shown to cause structural and functional neurocognitive changes in heavy users. Cannabis use initiation aligns with brain development trajectories; therefore, it is imperative that the potential neurological implications of cannabis use are understood. Males and females reach neurodevelopmental milestones at different rates making it necessary to consider biological sex in all cannabis and brain-based research. Through use of a systamatic review in accordance with PRISMA guidelines, we aimed to understand the interaction between biological sex and cannabis use on brain-based markers. In total, 18 articles containing a sex-based analysis of cannabis users were identified. While the majority of studies (n = 11) reported no sex by cannabis use interactions on brain-based markers, those that reported findings (n = 8) suggest females may be more susceptible to cannabis' neurotoxic effects. Unfortunately, a large portion of the literature was excluded due to no sex-based analysis. In addition, studies that reported no sex differences often contained a reduced number of females which may result in some studies being underpowered for sex-based analyses, making it difficult to draw firm conclusions. Suggestions to improve cannabis and sex-based reseach are proposed.

Long-acting injectable antipsychotic (LAI) prescribing trends during COVID-19 restrictions in Canada: a retrospective observational study.

BACKGROUND: The COVID-19 pandemic has had significant impacts on how mental health services are delivered to patients throughout Canada. The reduction of in-person healthcare services have created unique challenges for individuals with psychotic disorders that require regular clinic visits to administer and monitor long-acting injectable antipsychotic medications. METHODS: To better understand how LAI usage was impacted, national and provincial patient-level longitudinal prescribing data from Canadian retail pharmacies were used to examine LAI prescribing practices during the pandemic. Prescribing data on new starts of medication, discontinuations of medications, switches between medications, antipsychotic name, concomitant medications, payer plan, gender and age were collected from January 2019 to December 2020 for individuals ≥18-years of age, and examined by month, as well as by distinct pandemic related epochs characterized by varying degrees of public awareness, incidence of COVID-19 infections and public health restrictions. RESULTS: National, and provincial level data revealed that rates of LAI prescribing including new starts, discontinuations and switches between LAI products remained highly stable (i.e., no statistically significant differences) throughout the study period. CONCLUSIONS: Equal numbers of LAI new starts and discontinuations prior to and during the pandemic suggests prescribing of LAI antipsychotics, for those already in care, continued unchanged throughout the pandemic. The observed consistency of LAI prescribing contrasts with other areas of healthcare, such as cardiovascular and diabetes care, which experienced decreases in medication prescribing during the COVID-19 pandemic.

Toward individualized prediction of seizure recurrence: Hippocampal neuroimaging features in a cohort of patients from a first seizure clinic.

PURPOSE: We performed an exploratory analysis of electroencephalography (EEG) and neuroimaging data from a cohort of 51 patients with first seizure (FS) and new-onset epilepsy (NOE) to identify variables, or combinations of variables, that might discriminate between clinical trajectories over a one-year period and yield potential biomarkers of epileptogenesis. METHODS: Patients underwent EEG, hippocampal and whole brain structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) within six weeks of the index seizure, and repeat neuroimaging one year later. We classified patients with FS as having had a single seizure (FS-SS) or having converted to epilepsy (FS-CON) after one year and performed logistic regression to identify combinations of variables that might discriminate between FS-SS and FS-CON, and between FS-SS and the combined group FS-CON + NOE. We performed paired t-tests to assess changes in quantitative variables over time. RESULTS: Several combinations of variables derived from hippocampal structural MRI, DTI, and MRS provided excellent discrimination between FS-SS and FS-CON in our sample, with areas under the receiver operating curve (AUROC) ranging from 0.924 to 1. They also provided excellent discrimination between FS-SS and the combined group FS-CON + NOE in our sample, with AUROC ranging from 0.902 to 1. After one year, hippocampal fractional anisotropy (FA) increased bilaterally, hippocampal radial diffusivity (RD) decreased on the side with the larger initial measurement, and whole brain axial diffusivity (AD) increased in patients with FS-SS; hippocampal volume decreased on the side with the larger initial measurement, hippocampal FA increased bilaterally, hippocampal RD decreased bilaterally and whole brain AD, FA and mean diffusivity increased in the combined group FS-CON + NOE (corrected threshold for significance, q = 0.017). CONCLUSION: We propose a prospective, multicenter study to develop and test models for the prediction of seizure recurrence in patients after a first seizure, based on hippocampal neuroimaging. Further longitudinal neuroimaging studies in patients with a first seizure and new-onset epilepsy may provide clues to the microstructural changes occurring at the earliest stages of epilepsy and yield biomarkers of epileptogenesis.

Potential therapeutic benefits of cannabinoid products in adult psychiatric disorders: A systematic review and meta-analysis of randomised controlled trials.

The utility of cannabinoids and cannabinoid-based products (CBPs) as a pharmacological aid to treat psychiatric disorders in adulthood is still poorly understood despite a number of comprehensive general reviews discussing the topic. With a focus on randomized controlled trial (RCT) data, this review and meta-analysis aimed to aggregate and evaluate all current high-quality (Level-1) research that specifically assessed the effectiveness of a CBP on a diagnosed adult psychiatric disorder. The following databases, from their inception to September 2020, were included in the search: Academic Search Premier, PubMed, Ovid MEDLINE®, Web of Science™, PsycARTICLES, PsycINFO, CINAHL (Nursing and Allied Health), and Scopus. Risk of bias for each study was individually assessed using the revised Cochrane tool. Of the 2397 papers identified, thirty-one RCTs met criteria for inclusion: ten trials focused on treating cannabis use disorder, six on schizophrenia, five on opioid/tobacco use disorder, three on anxiety disorders, two on Tourette's disorder, two on anorexia nervosa, and one trial each for attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and obsessive compulsive disorder. This review finds limited evidence for the effectiveness of CBPs to acutely treat a narrow range of psychiatric symptoms. We report no evidence supporting the mid- to long-range effectiveness of any currently available CBP. In general, quality of the evidence was assessed as low- to moderate. Importantly, none of the studies discussed in this review presently endorse the use of cannabis flower as a method of treatment for any recognized psychiatric disorder. Larger, hypothesis driven RCTs are required prior to making further therapeutic recommendations.

Diagnostic performance and radiation dose of reduced vs. standard scan range abdominopelvic CT for evaluation of appendicitis.

OBJECTIVE: To compare the diagnostic performance and radiation dose of reduced vs. standard scan range CT in diagnosing appendicitis. METHODS: We retrospectively evaluated 531 consecutive adults who underwent emergency contrast-enhanced CT for abdominal pain or suspected appendicitis between July 2018 and March 2019. One hundred eighty-one young adults (mean age, 26 ± 6 years) were imaged from L2 to the symphysis pubis (reduced protocol). A total of 350 older patients (mean age, 55 ± 17 years) and those with a wider differential diagnosis were imaged from the diaphragm to the ischium (standard protocol). The reference standard was histopathology (surgical cases) or 3 months of medical record follow-up (nonsurgical cases). Sensitivity, specificity, and accuracy were calculated. Mean dose-length products (DLP) were compared (t-test). Using an anthropomorphic phantom, organ doses were measured on CT scanners with (scanner 1) and without (scanner 2) automatic voltage selection; effective radiation doses were calculated. RESULTS: The frequency of appendicitis was 57/181 (31.5%) and 80/350 (22.9%) in the reduced and standard groups, respectively. Results of the reduced and standard protocols respectively were as follows (95% CI in parentheses): sensitivity, 98.2% (90.4-99.9%) and 100.0 (95.3-100.0%); specificity, 99.2% (95.6-100.0%) and 99.6% (97.9-100.0%); accuracy, 97.8% and 97.4%; mean DLPs, 363 ± 191mGy∙cm and 633 ± 591mGy∙cm (p < 0.0001). Phantom-based measurements of effective dose were 47% lower on scanner 1 (4.64 vs. 2.48 mSv) and 26% lower on scanner 2 (4.68 vs. 3.45 mSv) with the reduced protocol. CONCLUSION: For young adults with clinically suspected appendicitis, a reduced scan range CT protocol is as sensitive, specific, and accurate as a standard scan range CT and imparts significantly less radiation dose. KEY POINTS: • A reduced scan range CT protocol in young adults with high suspicion of appendicitis demonstrates similar diagnostic performance as a full-range abdominopelvic CT in undifferentiated adult patients. • The reduced scan range CT protocol imparts significantly less radiation dose: 57% based on dose-length product data and 26-47% based on anthropomorphic phantom data.

When Cannabis Use Goes Wrong: Mental Health Side Effects of Cannabis Use That Present to Emergency Services.

Cannabis use is a modifiable risk factor for the development and exacerbation of mental illness. The strongest evidence of risk is for the development of a psychotic disorder, associated with early and consistent use in youth and young adults. Cannabis-related mental health adverse events precipitating Emergency Department (ED) or Emergency Medical Services presentations can include anxiety, suicidal thoughts, psychotic or attenuated psychotic symptoms, and can account for 25-30% of cannabis-related ED visits. Up to 50% of patients with cannabis-related psychotic symptoms presenting to the ED requiring hospitalization will go on to develop schizophrenia. With the legalization of cannabis in various jurisdiction and the subsequent emerging focus of research in this area, our understanding of who (e.g., age groups and risk factors) are presenting with cannabis-related adverse mental health events in an emergency situation is starting to become clearer. However, for years we have heard in popular culture that cannabis use is less harmful or no more harmful than alcohol use; however, this does not appear to be the case for everyone. It is evident that these ED presentations should be considered another aspect of potentially harmful outcomes that need to be included in knowledge mobilization. In the absence of a clear understanding of the risk factors for mental health adverse events with cannabis use it can be instructive to examine what characteristics are seen with new presentations of mental illness both in emergency departments (ED) and early intervention services for mental illness. In this narrative review, we will discuss what is currently known about cannabis-related mental illness presentations to the ED, discussing risk variables and outcomes both prior to and after legalization, including our experiences following cannabis legalization in Canada. We will also discuss what is known about cannabis-related ED adverse events based on gender or biological sex. We also touch on the differences in magnitude between the impact of alcohol and cannabis on emergency mental health services to fairly present the differences in service demand with the understanding that these two recreational substances may impact different populations of individuals at risk for adverse events.

Are There Therapeutic Benefits of Cannabinoid Products in Adult Mental Illness?

A position statement developed by the Canadian Psychiatric Association's (CPA) Research Committee and approved by the CPA's Board of Directors on May 13, 2020.

A Retrospective Study of the Clinical Characteristics Associated with Alcohol and Cannabis use in Early Phase Psychosis.

OBJECTIVE: Alcohol and cannabis misuse are common in patients with early phase psychosis (EPP); however, research has tended to focus primarily on cannabis misuse and EPP outcomes, with a relative lack of data on alcohol misuse. This retrospective cross-sectional EPP study investigated the relationship between cannabis, alcohol, and cannabis combined with alcohol misuse, on age, gender, psychotic, depressive and anxiety symptom severity, and social/occupational functioning, at entry to service. METHODS: Two-hundred and sixty-four EPP patients were divided into 4 groups based on substance use measured by the Alcohol, Smoking and Substance Involvement Screening Test: (1) no to low-level cannabis and alcohol misuse (LU), (2) moderate to high alcohol misuse only (AU), (3) moderate to high cannabis misuse only (CU), and (4) moderate to high alcohol and cannabis misuse (AU + CU). RESULTS: We found significant between group differences in age (with the AU group being the oldest and AU + CU group the youngest) as well as gender (with the CU group having the highest percentage of men). There were also group differences in positive psychotic symptoms (lowest in AU group), trait anxiety (highest in AU + CU group), and social/occupational functioning (highest in AU group). Further regression analyses revealed a particularly strong relationship between AU + CU group and trait anxiety (3-fold increased odds of clinical trait anxiety for combined misuse of alcohol and cannabis compared to non/low users). CONCLUSIONS: This study demonstrates the unique demographic and clinical characteristics found in the EPP population at entry to care associated with alcohol and cannabis misuse both separately and in combination. This work highlights the importance of including the assessment of alcohol misuse in addition to cannabis misuse in future treatment guidelines and research.

Claymation art therapy in early phase psychosis: A qualitative study to explore participants' experiences with the program and identify outcome effects.

AIM: Art therapy is a complex intervention that has mixed evidence for people with schizophrenia and scant research in early phase psychosis. Benefits appear to depend on level of engagement and more qualitative studies are needed to elucidate how it works and what outcomes to measure. The purpose of this study was to determine the feasibility of a 13-week Claymation art therapy group intervention for young adults with early phase psychosis, and to explore participants' experiences with the program and to identify outcome effects. METHODS: Thirteen participants completed the intervention in two cohorts. The participants' experiences were explored through qualitative thematic analysis of individual interviews postintervention and at 3-month follow-up. RESULTS: The program had a 62% retention rate and an 80% attendance rate. Qualitative analysis of postintervention and 3-month follow-up interviews identified six themes that described program elements: (a) Claymation valued; (b) film screening fostered support; (c) getting to know each other through art; (d) connecting with others with lived experience; (e) opportunity to build skills; and (f) supportive facilitators. Five themes were identified as outcome effects from both time points: (a) stress relief; (b) self-discovery; (c) pride in art; (d) confidence and hope; and (e) engagement in meaningful activity postintervention. Two themes were unique to the 3-month follow-up interviews: (a) Claymation was enabling and (b) showing my film. CONCLUSIONS: This group Claymation art therapy intervention effectively engaged people with early phase psychosis and the qualitative analysis identified program elements and outcome effects that can be evaluated in future studies.

Initial presentation of lung cancer in the emergency department: a descriptive analysis.

BACKGROUND: Guidelines aimed at improving care for lung cancer, the leading cause of cancer-related death in Canada and worldwide, require accurate knowledge of the diagnostic setting or pathway. We sought to determine how often lung cancer is initially diagnosed through the emergency department. METHODS: We performed a descriptive study that included all cases of primary lung cancer diagnosed in residents of Nova Scotia in 2014. Cancer registry data included diagnostic data and date of death to Aug. 31, 2016. We reviewed linked hospital records, including laboratory and imaging results, to identify the first positive diagnostic study and the route of presentation (emergency department v. other). We evaluated time from diagnosis to death as a function of presentation route using Kaplan-Meier curves and Cox regression (hazard rate ratios [HRRs]). RESULTS: Sufficient data were available for 946 of 951 cases identified, of which 336 (35.5%) were diagnosed through the emergency department. Cases diagnosed via the emergency department were more likely to be at an advanced stage (stage IV, 59.5% v. 43.4%), with patients experiencing shorter survival (1-yr survival, 28.4% v. 49.5%), including stage-specific survival. Mortality for cases diagnosed in the emergency department was 54% higher than for the non-emergency department group after adjusting for age and stage (HRR 1.54, 95% confidence interval 1.32-1.81). Few patients (7.1%, n = 24) who presented to the emergency department reported having no family physician. INTERPRETATION: The emergency department is a common route of presentation for lung cancer and is associated with advanced stage at diagnosis and reduced survival time. Strategies are needed to encourage pre-emergent diagnosis and to ensure that emergency providers are supported in the initial care of patients with lung cancer.

Corrigendum: Confused Connections? Targeting White Matter to Address Treatment Resistant Schizophrenia.

[This corrects the article DOI: 10.3389/fphar.2018.01172.].

Confused Connections? Targeting White Matter to Address Treatment Resistant Schizophrenia.

Despite development of comprehensive approaches to treat schizophrenia and other psychotic disorders and improve outcomes, there remains a proportion (approximately one-third) of patients who are treatment resistant and will not have remission of psychotic symptoms despite adequate trials of pharmacotherapy. This level of treatment response is stable across all stages of the spectrum of psychotic disorders, including early phase psychosis and chronic schizophrenia. Our current pharmacotherapies are beneficial in decreasing positive symptomology in most cases, however, with little to no impact on negative or cognitive symptoms. Not all individuals with treatment resistant psychosis unfortunately, even benefit from the potential pharmacological reductions in positive symptoms. The existing pharmacotherapy for psychosis is targeted at neurotransmitter receptors. The current first and second generation antipsychotic medications all act on dopamine type 2 receptors with the second generation drugs also interacting significantly with serotonin type 1 and 2 receptors, and with varying pharmacodynamic profiles overall. This focus on developing dopaminergic/serotonergic antipsychotics, while beneficial, has not reduced the proportion of patients experiencing treatment resistance to date. Another pharmacological approach is imperative to address treatment resistance both for response overall and for negative symptoms in particular. There is research suggesting that changes in white matter integrity occur in schizophrenia and these may be more associated with cognition and even negative symptomology. Here we review the evidence that white matter abnormalities in the brain may be contributing to the symptomology of psychotic disorders. Additionally, we propose that white matter may be a viable pharmacological target for pharmacoresistant schizophrenia and discuss current treatments in development for schizophrenia that target white matter.

Microstructural Findings in White Matter Associated with Cannabis and Alcohol Use in Early-Phase Psychosis: A Diffusion Tensor Imaging and Relaxometry Study.

Accumulating evidence suggests that brain white matter (WM) abnormalities may be central to the pathophysiology of psychotic disorders. In addition, there is evidence that cannabis use and alcohol use each is associated with WM abnormalities. However, there are very limited data on the effects of these substances on WM microstructure in patients with psychosis, especially for those at the early phase of illness. This project aimed to examine the impact of cannabis use and alcohol use on WM tissue in early-phase psychosis (EPP). WM was investigated in 21 patients with EPP using diffusion tensor imaging (DTI) and transverse relaxation time of tissue water (T2), with the primary outcomes being mean fractional anisotropy (FA) and T2. DTI analyses were performed at the full-brain level using tract-based spatial statistics with both DTI and T2 analysis done within a WM volume of interest (VOI) implicated in psychosis (containing the left superior longitudinal fasciculus). Our findings revealed that younger age of onset of regular alcohol use (more than one drink per week) was associated with lower FA values in the left thalamic radiation and left parahippocampal and left amygdalar WM. More frequent lifetime cannabis use was correlated with increased mean full-brain FA. There was no significant relationship found between FA and alcohol or cannabis use within the VOI. Relaxometry analysis revealed trend-level evidence of shortened T2 with later onset of regular alcohol use and with more frequent cannabis use. This study provides novel data demonstrating cortical and subcortical WM findings related to alcohol use in EPP and is the first to combine DTI and relaxometry, relating to this patient population.