The association between extent of chronic cannabis use (CCU-extent) and cognitive impairment among adolescents has been the subject of controversial debate. Linking DNA methylation to CCU-extent could help to understand cannabis associated changes in cognitive performance. We analyzed cognitive task performances, CpG methylation in peripheral whole-blood samples and self-reported past-year CCU-extent of n = 18 adolescents (n = 9 psychiatric outpatients with chronic cannabis use (CCU), n = 9 without) who were matched for age, gender and psychiatric disorders. Patients with CCU were at least 24 h abstinent when cognitive tasks were performed. A Principal Component Analysis (PCA) was carried out to identify group differences in whole genome DNA methylation. Mediation analyses were performed between CCU-extent associated CpG sites and CCU-extent associated variables of cognitive tasks. PCA results indicated large differences in whole genome DNA methylation levels between the groups that did not reach statistical significance. Six CpG sites revealed reduced methylation associated with CCU-extent. Furthermore, CCU-extent was associated with lower scores in verbal learning. All six CpG sites mediated the effects between CCU-extent and verbal learning free recall. Our results indicate that CCU is associated with certain patterns in the methylome. Furthermore, CCU-extent associated impairments in memory function are mediated via differential methylation of the six CCU-associated CpG sits. Six identified CpG are located in genes previously described in the context of neurodegeneration, hippocampus-dependent learning and neurogenesis. However, these results have to be carefully interpreted due to a small sample size. Replication studies are warranted.

The Brisbane Longitudinal Twin Study (BLTS) was being conducted in Australia and was funded by the US National Institute on Drug Abuse (NIDA). Adolescent twins were sampled as a part of this study and surveyed about their substance use as part of the Pathways to Cannabis Use, Abuse and Dependence project. The methods developed in this dissertation were designed for the purpose of analyzing a subset of the Pathways data that includes demographics, cannabis use metrics, personality measures, and imputed genotypes (SNPs) for 493 complete twin pairs (986 subjects.) The primary goal was to determine what combination of SNPs and additional covariates may predict cannabis use, measured on an ordinal scale as: “never tried,” “used moderately,” or “used frequently”. To conduct this analysis, we extended the ordinal Generalized Monotone Incremental Forward Stagewise (GMIFS) method for mixed models. This extension includes allowance for a unpenalized set of covariates to be coerced into the model as well as flexibility for user-specified correlation patterns between twins in a family. The proposed methods are applicable to high-dimensional (genomic or otherwise) data with ordinal response and specific, known covariance structure within clusters.

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.

Bien que la conduite d’un véhicule motorisé soit une activité des plus usuelles, les accidents routiers font partie des dix premières causes mondiales de décès. Au cours des dernières années, les programmes canadiens et québécois de prévention en sécurité routière ont montré une certaine efficacité, observable notamment par une baisse des décès sur la route. Ces progrès sont toutefois insuffisants, et de meilleures stratégies d’intervention et de prévention doivent être développées. Une meilleure connaissance des personnes susceptibles d’être impliquées dans des accidents routiers permettrait le développement de campagnes plus ciblées et pertinentes. Ainsi, il est déjà reconnu que le fait d’être un homme, le fait d’être âgé entre 15 et 29 ans, et la consommation d’alcool ou de substances psychoactives, augmentaient le risque d’être impliqué dans un accident routier. De ce fait, l’un des objectifs de cette thèse est de mieux comprendre le rôle de la fréquence de consommation de cannabis dans la conduite automobile risquée chez les jeunes conducteurs de sexe masculin. D’autre part, des études se sont déjà intéressées au rôle joué par les parents dans les comportements routiers de leurs jeunes. Aucune étude ne semble toutefois s’être attardée au rôle du soutien à l’autonomie prodigué par les parents dans la prise de risques au volant des jeunes. Le second objectif de cette thèse est donc d’investiguer l’impact du soutien parental de l’autonomie dans la conduite automobile des jeunes consommateurs de cannabis. Dans cette optique, l’Article 1 traite de l’association entre la fréquence de consommation de cannabis et la prise de risques au volant auto-rapportée auprès d’un échantillon de conducteurs masculins âgés entre 18 et 25 ans. De plus, il évalue le rôle du niveau de soutien parental de l’autonomie dans cette prise de risques auto-rapportée. Les résultats indiquent que la fréquence de consommation de cannabis est positivement associée à la prise de risques au volant, telle que mesurée par la variable de conduite sous l’influence du cannabis, et en est un prédicteur. Les résultats de cet article n’ont cependant pu démontrer que le soutien parental de l’autonomie était un prédicteur de la conduite automobile risquée auto-rapportée. L’Article 2 étudie la conduite automobile risquée à travers des données comportementales de conduite automobile risquée, observées dans un contexte de simulation de conduite. Les résultats de ce deuxième article révèlent que la fréquence de consommation de cannabis contribue à prédire la conduite automobile risquée observée. En outre, les résultats indiquent un effet significatif des niveaux de fréquence de consommation sur la prise de risques au volant. Finalement, les résultats révèlent une contribution du niveau de soutien parental à l’autonomie dans la prise de risques au volant observée en simulation. Enfin, la discussion porte sur les contributions théoriques de cette thèse aux connaissances scientifiques en sécurité routière, ainsi que ses implications pratiques pour la prévention et l’intervention. / Although driving a vehicle is one common activity, road accidents are one of the top ten causes of death in the world. In recent years, a decrease of on road deaths in Canada and Quebec have shown that road safety prevention campaigns can be effective. However, these advances are insufficient, and there is a need for better intervention and prevention strategies. A better knowledge of individuals likely to be involved in road accidents would allow the development of more targeted and relevant prevention campaigns. Thus, it is already known that men, individuals aged between 15 and 29, and users of alcohol or psychoactive substances before driving have an increased risk of being involved in a road accident. Therefore, one of the objectives of this thesis is to have a better understanding of the role of frequency of cannabis use in young males’ risky driving. Also, studies have already examined the role of parents in the road behaviors of their children. However, no study seems to have focused on the role of parental autonomy support in young drivers’ risky driving. The second objective of this thesis is to investigate the impact of parental autonomy support on risky driving among young cannabis users. In this line of thinking, Article 1 investigates the association between frequency of cannabis use and self-reported risky driving among a sample of male drivers aged between 18 and 25 years old. In addition, it evaluates the role of parental autonomy support in self-reported risky driving. Results indicate that frequency of cannabis use is positively associated with risky driving (measured with self-reported measure of driving under the influence of cannabis), and is a predictor of this measure. However, results did not show that parental autonomy support is a predictor of self-reported risky driving. Article 2 studies risky driving through behavioral measures. These behavioral measures are observed in a driving simulator. Results of this article reveal a contribution of frequency of cannabis use in predicting observed risky driving in a driving simulator. In addition, results indicate a significant effect of the frequency of use levels on risky driving behaviors observed in the simulated driving task. Finally, results show a contribution of parental autonomy support in observed risky driving in the simulator. The theoretical contributions of this thesis to the scientific literature on road safety, as well as its practical implications for prevention and intervention are discussed.

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.

Background: Risk perception has been studied concerning the use of marijuana and it impacts the intention to use that specific substance. Aim: The aim was to study the association between the perceived risk of cannabis use and cannabis use among Swedish youth after controlling for gender, age, and education. The aim was also to study whether the association between the perceived risk of cannabis use and cannabis use was different according to gender. Method: The thesis project was based on data from the Flash Eurobarometer 330 - Youth Attitudes on Drugs. Results: When age and education were controlled for, both among Swedish youth and among male participants, the perceived risk had an association with cannabis use - higher risk perception entailed a lower use. Discussion: The association between the perceived risk of cannabis use and cannabis use appears to be due to the impact of risk perception on behaviour. Conclusion: By preserving the risk perception that Swedish youth have of cannabis, it may be possible to protect them from the potential harm that cannabis use cause.

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.

Contexte : Les études sur l’association entre la consommation de cannabis et l’activité physique sont majoritairement transversales et rapportent des résultats contradictoires. Ce mémoire se penche sur la relation entre les trajectoires de consommation de cannabis et celles d’activité physique chez les jeunes adultes pour éclairer la recherche et informer la santé publique. Objectifs : Décrire 1) les trajectoires sexospécifiques d’activité physique modérée à vigoureuse (APMV) et d’usage régulier (1-7 jours/semaine) de cannabis (URC) des adultes de 20 à 35 ans et 2) la relation entre les trajectoires des deux comportements. Méthodes : Les données sur les 742 participants proviennent des cinq derniers cycles de l’étude longitudinale Nicotine Dependence in Teens. L’âge moyen des participants à chaque suivi est de 20,3, 24,0, 30,5, 33,6 et 35,2 ans. La méthode fondée sur le groupement de Nagin est utilisée pour identifier des trajectoires distinctes d’APMV et d’URC. Des probabilités conditionnelles reliant les trajectoires des deux comportements sont estimées pour décrire leur relation. Résultats : Les quatre trajectoires d’APMV et les deux trajectoires d’URC identifiées sont similaires chez les deux sexes. Les probabilités conditionnelles suggèrent que la trajectoire croissante d’APMV est associée à la trajectoire d’URC persistant chez les hommes et, dans une moindre mesure, chez les femmes. Conclusion : Il existe des trajectoires distinctes d’APMV et d’URC chez les jeunes adultes. Les individus, et plus particulièrement les hommes, qui ont des niveaux croissants d’APMV de 20 à 35 ans ont une probabilité accrue de consommer régulièrement du cannabis durant la même période. / Background: Most studies investigating the association between cannabis use and physical activity are cross-sectional and they report contradictory results. We investigated how cannabis use and physical activity co-occur over time among young adults to better understand their relationship and inform research and public health. Objectives: Describe 1) sex-specific trajectories of moderate-to-vigorous physical activity (MVPA) and regular (1-7 days/week) cannabis use (RCU) from age 20 to 35 and 2) associations between the trajectories of these two behaviors. Methods: A total of 742 participants from the five most recent cycles of the Nicotine Dependence in Teens longitudinal study provided MVPA and RCU data. Mean age at each cycle was 20.3, 24.0, 30.5, 33.6 and 35.2 years. Group-based trajectory modeling was used to identify distinct trajectories of MVPA and RCU. Conditional probabilities linking trajectories across behaviors were estimated to describe associations between MVPA and RCU trajectories. Results: The four MVPA trajectories and the two RCU trajectories identified were similar across sexes. Conditional probabilities suggested an association between the increasing MVPA trajectory and the trajectory of persistent RCU, more so among men than among women. Conclusion: Distinctive trajectories of MVPA and RCU exist in young adulthood. Individuals, and particularly men, with increasing MVPA levels from age 20 to 35 have an increased probability of RCU over the same age range.

The word 'marijuana' was introduced to Australia by the US Bureau of Narcotics via the Diggers newspaper, Smith's Weekly, in 1938. Marijuana was said to be 'a new drug that maddens victims' and it was sensationally described as an 'evil sex drug'. The resulting tabloid furore saw the plant cannabis sativa banned in Australia, even though cannabis had been a well-known and widely used drug in Australia for many decades. In 1964, a massive infestation of wild cannabis was found growing along a stretch of the Hunter River between Singleton and Maitland in New South Wales. The explosion in Australian marijuana use began there. It was fuelled after 1967 by US soldiers on rest and recreation leave from Vietnam. It was the Baby-Boomer young who were turning on. Pot smoking was overwhelmingly associated with the generation born in the decade after the Second World War. As the conflict over the Vietnam War raged in Australia, it provoked intense generational conflict between the Baby-Boomers and older generations. Just as in the US, pot was adopted by Australian Baby-Boomers as their symbol; and, as in the US, the attack on pot users served as code for an attack on the young, the Left, and the alternative. In 1976, the 'War on Drugs' began in earnest in Australia with paramilitary attacks on the hippie colonies at Cedar Bay in Queensland and Tuntable Falls in New South Wales. It was a time of increasing US style prohibition characterised by 'tough-on-drugs' right-wing rhetoric, police crackdowns, numerous murders, and a marijuana drought followed quickly by a heroin plague; in short by a massive worsening of 'the drug problem'. During this decade, organised crime moved into the pot scene and the price of pot skyrocketed, reaching $450 an ounce in 1988. Thanks to the Americanisation of drugs policy, the black market made 'a killing'. In Marijuana Australiana I argue that the 'War on Drugs' developed -- not for health reasons -- but for reasons of social control; as a domestic counter-revolution against the Whitlamite, Baby-Boomer generation by older Nixonite Drug War warriors like Queensland Premier, Bjelke-Petersen. It was a misuse of drugs policy which greatly worsened drug problems, bringing with it American-style organised crime. As the subtitle suggests, Marijuana Australiana relies significantly on 'alternative' sources, and I trawl the waters of popular culture, looking for songs, posters, comics and underground magazines to produce an 'underground' history of cannabis in Australia. This 'pop' approach is balanced with a hard-edged, quantitative analysis of the size of the marijuana market, the movement of price, and the seizure figures in the section called 'History By Numbers'. As Alfred McCoy notes, we need to understand drugs as commodities. It is only through a detailed understanding of the drug trade that the deeper secrets of this underground world can be revealed. In this section, I present an economic history of the cannabis market and formulate three laws of the market.