The legalization of cannabis is increasing across the United States, for both recreational and medical use. This has resulted in a change in public opinion regarding the risks of cannabis use. This is particularly true for the current generation of older adults, which experiences a greater prevalence of cannabis use than previous members of this cohort. Due to decreased perception of risk and medical or emotional issues associated with old age, older adults increasingly use cannabis to cope with their psychiatric and medical symptoms. Current studies provide evidence of an association between using cannabis for medical symptoms and the development of a Cannabis Use Disorder (CUD). However, there is a lack of literature addressing the association between types of symptoms treated with medical marijuana and developing symptoms of CUD. This study developed a survey using the Cannabis Use Disorder Identification Test (CUDIT) and measures for motives and symptoms of cannabis use. This was done to evaluate the presence of CUD symptoms in older adults (ages 55+) who used cannabis in the past six months while owning a Medical Marijuana License (MML). Data preparation included an examination of outliers, multicollinearity, and data distributions. The primary analysis regressed cannabis use pathology onto psychiatric motives and physical motives. The results of this study suggest that those utilizing cannabis for anxiety symptoms experience more symptoms of a cannabis use disorder. At the same time, there was a negative association between using cannabis order for medical symptoms and developing cannabis use disorder symptoms. Additionally, there was no correlation between the amount of cannabis used and its use for physical symptoms.

As legalization of cannabis continues to spread across the United States, many question the public health implications. The term “cannabis” is often used to refer to anything that comes from the plant and can be used recreationally (to get high or alter one’s current state) or medically (to treat a medical condition). While previous research has primarily focused on the impact of recreational cannabis use, few studies have examined cognitive outcomes associated with medical cannabis (MC) use and the potential for development of problematic use in MC patients. Given important distinctions among recreational users and MC patients, it is likely that these distinct populations of cannabis consumers will experience differential cognitive effects and potential for problematic cannabis use. This dissertation is comprised of three studies. The first is a cross-sectional study that explores executive function and verbal learning and memory in recreational cannabis users relative to healthy controls who do not use cannabis, while also assessing whether cannabis use patterns (e.g., age of onset, urinary THC levels) influence findings. The second study is an observational, longitudinal study which examines executive function and memory, as well as changes in mood, anxiety, sleep, and quality of life in MC patients over 12 months of MC treatment relative to pre-MC treatment. In the third study, symptoms and behaviors associated with problematic cannabis use are examined in cohorts from study 1 and study 2. Specifically, scores on the Cannabis Use Disorder Identification Test – Revised (CUDIT-R) are assessed in MC patients over the course of treatment and also compared to a previously recruited cohort of recreational cannabis users; the validity of the CUDIT-R is also explored. Despite previous research, in the current study recreational users did not exhibit cognitive decrements relative to healthy controls. In MC patents, cognitive performance was stable over the course of 12 months of MC treatment relative to pre-MC treatment performance, and overall they reported improved ratings of mood, anxiety, sleep, and some aspects of quality of life. Although the CUDIT-R suggests MC patients’ average scores do not meet the threshold for possible cannabis use disorder, analyses revealed this measure is not valid and therefore not appropriate in MC patients. Although changes in cognition were not detected in recreational users or MC patients in the current studies, a number of methodological limitations (e.g., sample size and limited ability to adjust for confounding variables) must be considered as these factors likely affected study results. Future studies evaluating the impact of cannabis use will benefit from carefully considering the definition of cannabis itself, goal of use, product choice, and age of onset of use. Researchers and clinicians will also benefit from the development of screening tools specifically designed to assess cannabis use disorder in those who use cannabis for medical purposes.

Cannabis use is becoming increasingly prevalent in Canada and the United States, where legality and public perception have recently shifted to be more permissive of recreational use. Despite established negative health consequences associated with persistent use, there remains considerable debate in the scientific community surrounding the potentially harmful effects of cannabis use on human cognition. Evidence exists that heavy cannabis use predicts diminished performance within several neurocognitive domains and also predicts greater risk of having ADHD. Further evidence suggests that earlier age of first cannabis use strengthens these associations, however the findings in these literatures are mixed and in need of further delineation. This thesis sought to examine continuous associations among current cannabis use severity, age of first use, neuropsychological performance, and ADHD symptomatology. Two studies using large samples of community adults were conducted. Study 1 analyzed data from the Human Connectome Project, and examined performance on a battery of neuropsychological measures among young adults, and found recent use to be the strongest predictor of differences in episodic memory and processing speed, and CUD predicted lower fluid intelligence. Lifetime exposure to cannabis was not associated with any outcome measures. Study 2 examined similar associations in a sample of adults representative of the Hamilton community, and also included self-reported symptoms of ADHD. Study 2 found current cannabis use severity to be predictive of more impulsive reward preferences, and also of both hyperactive-impulsive and inattentive symptoms of ADHD. Both studies found a lack of support for the role of age of first cannabis use in differential cognitive performance, and also failed to find associations between cannabis involvement and several cognitive domains such as working memory, behavioural inhibition, executive function, and psychomotor dexterity. These findings challenge some of the current literature, and highlight the necessity of further investigation to better understand interrelationships among cannabis use, cognition, and ADHD. / Thesis / Master of Science (MSc) / It is unclear to what extent cannabis use effects mental functions such as memory, attention, and intelligence. The goal of this research was to investigate how recent and early-life cannabis use is related to these cognitive functions and real-life problems with attention and impulse control as seen in ADHD. Two studies were performed to investigate these relationships, and together found recent cannabis use rather than lifetime use to be predictive of performance on select cognitive abilities and ADHD symptoms. Age of first cannabis use and lifetime use were not associated with differences in cognition, suggesting that cannabis use in adolescence may not necessarily cause lasting detrimental changes. Rather, people who have symptoms of ADHD may be more likely to use cannabis earlier and in more problematic ways.

Lack of a brief empirically-verified screener for problematic and potentially problematic cannabis use has hampered implementation of a proactive opportunistic cannabis screening and early intervention (SEI) initiative in New Zealand. Addressing this instrumentation need was the primary aim of this thesis. This thesis also investigated the nature, prevalence, severity, and natural history of cannabis-related problems among a heterogeneous sample of 212 ‘at risk’ adolescent and adult users recruited from the community. In a 3-phase developmental design the CUPIT question candidates were first generated employing an Expert Panels methodology. The CUPIT structure, crosssectional, and longitudinal psychometric properties were then systematically tested, incorporating measures of cannabis-related pathology and DSM-IV/ICD-10 diagnoses of cannabis use disorders as criterion standard. High levels of cannabis consumption and related health and psychosocial problems reported portrayed a highly-disordered sample, most marked among adolescents. DSMIV/ICD-10 diagnoses were almost universal with no significant adolescent/adult differences in dependence symptoms count or severity. The two CUPIT subscales (Impaired Control, Problems) derived from principal components analyses exhibited good test-retest and internal consistency reliability and highly significant ability to discriminate diagnostic subgroups along the severity continuum (nonproblematic, risky, problematic use). At the 12-month follow-up, 194 adolescents and adults reported significantly increased cannabis consumption (adolescents), symptoms, and dependence severity. Baseline CUPIT subscale scores demonstrated highly significant longitudinal predictive utility for respondents’ diagnostic group membership, health and psychosocial problems, and significantly improved prediction of other measured outcomes in conjunction with age and gender. ROC analyses identified a CUPIT score of 12 to be the optimal cut-point for maximum sensitivity for both currently diagnosable cannabis use disorder and those ‘at risk’ in this sample. The empirical findings of this thesis research provide a compelling rationale for systematic implementation of opportunistic SEI among consumers of publicly-funded health and social services in New Zealand. Data confirmed that the vast majority of those needing help are unaware, or do not perceive, they need help. This thesis argues that, facilitated by the CUPIT, reliable proactive detection and appropriate intervention for early-stage cannabis use problems has potential for enormous cumulative impact on public health gains and the individual’s quality of life.

Efforts to objectively inform cannabis discourses include research on the epidemiology of cannabis abuse and dependence disorders or, collectively, cannabis use disorder (CUD). For my dissertation I identified classes of individuals based on intraindividual CUD trajectory patterns and contrasted trajectory classes with respect to clinical characteristics of CUD, developmental risk factors, and psychosocial outcomes. Identifying differences between trajectory classes provides evidence for the validity of trajectory-based CUD constructs and informs the development of comprehensive models of CUD epidemiology and trajectory-specific intervention approaches. My dissertation used data from the Oregon Adolescent Depression Project, a prospective epidemiological study of the psychiatric and psychosocial functioning of a representative community-based sample randomly selected from nine high schools across western Oregon. Four waves of data collection occurred between mid-adolescence and early adulthood and included diagnostic interviews and self-report questionnaires. Onset and offset ages of all CUD episodes were recorded. The reference sample included 816 participants who completed all diagnostic interviews. A series of latent class growth models revealed three distinct CUD trajectory classes through age 30: (1) a persistent increasing risk class; (2) a maturing out class, marked by increasing risk through age 20 and then a decreasing risk through early adulthood; and (3) a stable low risk class. Rates of cannabis dependence were similar across the persistent increasing and the maturing out classes. Trajectory classes characterized by a history of CUD were associated with a variety of childhood risk factors and measures of psychosocial functioning during early adulthood. Participants who were male, had externalizing disorders, and had psychotic experiences during early adulthood discriminated between the persistent increasing and the maturing out classes. Future research based on more diverse samples is indicated, as are well-controlled tests of associations between risk factors, trajectory class membership, and psychosocial outcomes. A better understanding of these relationships will inform etiological theories of CUD and the development of effective intervention programs that target problematic cannabis use at specific developmental stages. Designing targeted versus undifferentiated interventions for those at greatest risk for adult psychosocial impairment could be a cost-effective way to mitigate the consequences of CUD.

Background: Polysubstance use (PSU) is common among patients with cannabis use (CU) and is related to more severe CU problems. However, it is unclear how PSU predicts CU treatment outcomes beyond CU patterns. We examined the frequency, amount, and class of additionally used substances as predictors for primary and secondary outcomes. Methods: We conducted crude and adjusted regression analyses for PSU variables as predictors of remission, abstinence, reduction, and secondary outcomes in 166 help-seeking patients from a randomized clinical trial of CANDIS, a cognitive behavioral treatment program. Results: Patients with recent illegal PSU experienced more difficulties in reducing their CU (B = –1.22, p < 0.001). In contrast, remission rates were slightly higher in patients with a wide variety of last-year-PSU (RD = 0.04, p < 0.001). Amphetamine use predicted poorer outcomes regarding CU-related problems (B = –4.22, p = 0.019), and the use of opiates, inhalants, and dissociative substances predicted poorer physical health outcomes (B = –0.62, p = 0.009; B = –0.96, p = 0.039; B = –1.18, p = 0.007). Conclusions: CU treatment is also effective for patients with moderate PSU. However, treatment effects may be enhanced by addressing specific PSU characteristics as part of a modularized program.

Malgré de nombreux efforts de prévention, les jeunes conducteurs sont surreprésentés dans les accidents routiers. Certaines études ont visé à mettre en évidence les facteurs pouvant influencer les jeunes conducteurs à adopter des comportements risqués. La consommation de cannabis et l’impulsivité ont été identifiées comme des facteurs importants. L’objectif de cette thèse vise à mieux comprendre les liens entre la consommation de cannabis et les comportements routiers risqués, tout en tenant compte de l’impulsivité. Pour ce faire, cette thèse se divise en deux articles. Le premier article vise à vérifier si la fréquence de consommation de cannabis prédit la prise de risque des jeunes conducteurs au-delà de l’effet de leur impulsivité. 209 participants âgés de 17 à 25 ans ont rempli des questionnaires sur leurs comportements routiers, leur impulsivité, et leur fréquence de consommation de cannabis. Les résultats montrent que la fréquence de consommation de cannabis prédit la prise de risque des jeunes conducteurs au-delà de l’effet de l’impulsivité. De plus, l’urgence positive est la seule facette de l’impulsivité qui prédit la prise de risque, indépendamment des habitudes de consommation. Plusieurs hypothèses pouvant expliquer ces résultats ont été proposées dont une qui nous semblait particulièrement pertinente : la probabilité de prendre le volant après avoir consommé est plus élevée dans le cas d’une consommation plus fréquente, ainsi l’effet direct de la substance pourrait expliquer les comportements risqués. C’est pourquoi dans notre deuxième étude, nous avons voulu vérifier si la consommation de cannabis était associée aux comportements risqués même lorsque le consommateur n’est pas sous l’effet du cannabis. Comme une consommation fréquente peut être symptomatique d’un trouble d’utilisation du cannabis (TUC), nous avons voulu vérifier son impact sur les comportements risqués. Le deuxième article compare donc un groupe de consommateurs ayant un TUC avec un groupe n’en ayant pas sur des comportements risqués tout en tenant compte de leur impulsivité. Pour ce faire, 76 participants masculins, consommateurs de cannabis, âgés de 18 à 25 ans, ont complété une tâche de simulation de conduite ainsi qu’une tâche stop-signal, s’étant abstenus de 6 consommer du cannabis dans les 12 heures précédant l’expérimentation. Ils ont aussi rempli des questionnaires sur les habitudes de consommation de cannabis, les traits d’impulsivité et la prise de risque. Les consommateurs ayant un TUC ont manifesté plus de comportements risqués dans le simulateur que ceux n’en ayant pas, quel que soit leur niveau d’impulsivité et sans être sous l’effet de la substance. Plusieurs explications ont été proposées : difficulté d’adaptation à la conduite sans l’effet de la substance; présence d’une autre variable confondante que l’impulsivité sous-jacente à la consommation et aux comportements risqués; effet résiduel de la substance, non détecté par la tâche stop-signal, qui influencerait les comportements routiers. En résumé, il ressort de cette thèse que la consommation de cannabis est un facteur contribuant aux comportements risqués des jeunes conducteurs, et ce indépendamment de l’impulsivité. De plus, les consommateurs ne constituent pas un groupe homogène, d’où la pertinence de cibler particulièrement les consommateurs problématiques dans les campagnes de prévention. / Despite many prevention efforts, young drivers are overrepresented in road crashes. Some studies show that cannabis use and impulsivity are significant predictors of risky driving behaviour among young drivers. The aim of this thesis is to better understand the association between cannabis use and risky driving behaviour, while considering the driver’s impulsivity. For this purpose, this thesis is divided into two articles. The first article aims to verify whether the frequency of cannabis use predicts risk-taking over and above the impulsivity traits of young drivers. 209 participants aged between 17 and 25 completed questionnaires on their driving behaviours, impulsivity, and frequency of cannabis use. Results show that the frequency of cannabis use is a significant predictor of risky driving over and above the five impulsivity traits. Furthermore, positive urgency is the only impulsivity trait which predicts risky driving, regardless of the frequency of cannabis use. Several explanations of these results are proposed, including one we found particularly relevant: the probability of driving under the influence is higher with more frequent use, so the substance effects could explain risky driving behaviour. Therefore, in our second study, we wanted to test whether cannabis use was associated with risky driving behaviour even if the user was not driving under the influence. Moreover, since frequent use can be symptomatic of a cannabis use disorder (CUD), we wanted to verify its impact on risky behaviours. The second article, therefore, compares two groups of cannabis users (with or without CUD) on several driving behaviours, while considering their impulsivity. A sample of 76 male participants, cannabis users, aged 18 to 25, completed a driving simulation task and a stop-signal task, abstaining from cannabis use in the 12 hours preceding the experiment. They also completed questionnaires about their cannabis use patterns, impulsivity traits and risk-taking. Results show that users with a CUD displayed more risky behaviours in the simulator than users without a CUD, regardless of their impulsivity level and without being under the effects of the substance. Several explanations have been proposed: difficulty adjusting to driving without the influence of the substance for users with a CUD; presence of a confounding variable different from the impulsivity; or residual effects of cannabis, not detected by the stop-signal task. In summary, this thesis emphasizes that cannabis use is a contributing factor to young drivers’ risky behaviours, regardless of their impulsivity. Moreover, cannabis users are not a homogeneous group, which is why it is important to specifically target problematic users in prevention campaigns.

Le trouble de l’usage de cannabis (TLUC) est une problématique complexe particulièrement lorsqu’il est comorbide à un trouble mental sévère (TMS). D’une part, aucune pharmacothérapie n’a été approuvée pour son traitement et d’une autre part, les psychothérapies existantes offrent au mieux une efficacité faible et non maintenue dans le temps. L’émergence de la réalité virtuelle (RV) en psychiatrie pourrait augmenter l’efficacité considérant le potentiel qu’elle a démontré pour une variété de conditions psychiatriques. Actuellement, aucune intervention ayant incorporé la RV visant le traitement du TLUC n’a fait l'objet de recherche. L’intervention Avatar pour le TLUC se veut une approche innovante utilisant la RV en tant qu’outil thérapeutique afin de faire des apprentissages et les pratiquer au moment où les cravings et les émotions sont d’intensité similaire à celle de leur quotidien. Cette intervention comprenant huit séances utilise des techniques provenant de thérapie recommandée (ex., thérapie cognitivo-comportementale, entrevue motivationnelle). Durant les périodes d’immersion, les participants ont interagi avec un avatar représentant une personne significative en lien avec leur consommation dont le thérapeute joue le rôle. Cet essai clinique pilote a visé l’évaluation de l’efficacité ainsi que la faisabilité et l’acceptabilité à court terme chez 19 participants ayant un double diagnostic de TMS et TLUC. Les résultats ont montré une réduction significative modérée de la quantité de cannabis consommée (d=0,545; p=0,017), laquelle a été confirmée par quantification du THC-COOH dans les urines. Une tendance a été observée pour la fréquence de l’usage (d=0,313; p=0,052). Concernant la sévérité du TLUC et la motivation aux changements, une petite (d=0,474; p=0,046) et modérée (d=0,523; p=0,046) taille d’effet ont été obtenues respectivement. Aucun effet significatif n’a été observé pour la qualité de vie et les symptômes psychiatriques sont restés stables. Les résultats à moyen et long terme seront évalués lorsque les participants auront terminé les suivis à 3, 6 et 12 mois. Un essai randomisé contrôlé à simple insu comparant l’intervention Avatar pour TLUC à une intervention classique en toxicomanie est en cours. / Cannabis use disorder (CUD) is a complex issue, particularly when it is comorbid with a severe mental disorder (SMD). On one hand, no pharmacotherapy has been approved for its treatment. On the other hand, existing psychotherapies offer, at best, low efficacy that is not sustained over time. The emergence of virtual reality (VR) in psychiatry could increase efficacy, given the potential it has demonstrated for a variety of psychiatric conditions. To date, no intervention incorporating VR for the treatment of CUD has been developed. The Avatar intervention for CUD is an innovative approach using VR as a therapeutic tool to learn and practice in real-time when cravings and emotions are of similar intensity to their everyday lives. This eight-session intervention uses techniques from commonly used therapeutic approaches (e.g., cognitive-behavioral therapy, motivational interviewing). During immersive sessions, participants interacted with an avatar played by the therapist, representing a significant person intrinsically linked with their consumption. This pilot clinical trial was designed to assess efficacy at short-term, feasibility, and acceptability in 19 participants with a dual diagnosis of SMD and CUD. Results showed a significant moderate reduction in the amount of cannabis consumed (d=0.545, p=0.017), which was confirmed by the quantification of THC-COOH in urine. Regarding the severity of TLUC and motivation to change, a small (d=0.474; p=0.046) and moderate (d=0.523; p=0.046) effect size were obtained, respectively. No significant effect was obtained for quality of life, and psychiatric symptoms remained stable. Once participants have completed the 3-, 6- and 12-month follow-ups, medium- and long-term results will also be assessed. A single-blind randomized controlled trial is currently underway to compare the Avatar intervention for CUD with a conventional addiction intervention.