Nous avons montré : a) qu’il existe un lien entre la consommation de cannabis et la présence de sténoses artérielles intracrâniennes multifocales chez le jeune adulte victime d’infarctus cérébral, b) que la prévalence des sténoses artérielles intracrâniennes atteint un tiers des cas dans une cohorte de 159 infarctus cérébraux du jeune adulte, c) que 13% des infarctus cérébraux dans cette série répondent aux critères angiographiques du syndrome de vasoconstriction cérébrale réversible déclenché majoritairement par la consommation de cannabis, d) que le tétrahydrocannabinol (THC, le principal produit actif du cannabis) inhibe in vitro la chaîne respiratoire mitochondriale de cerveau de rat, et induit une génération significative de peroxyde d’hydrogène. La génération de radicaux libres pourrait être un des mécanismes possibles de toxicité cérébrale du THC en jeu lors d’un infarctus cérébral. / We showed that: a) there was a link between cannabis use and intracranial arterial multifocal stenosis in a series of ischemic stroke in the young, b) the prevalence of intracranial arterial stenosis was up to 31% in a series of 159 ischemic strokes in the young, c) 13% of the patients in this series sustained the angiographic criteria of reversible cerebral vasoconstriction syndrome, and that the precipitating factor was the use of cannabis in 67% of cases, d) tetrahydrocannabinol (THC, the main active component in cannabis) inhibits the respiratory mitochondrial chain of the brain in rats and induces a significant production of hydrogen peroxide. These results suggest that one of the mechanisms of brain toxicity induced by cannabis in ischemic stroke patients, may be the high rate of generation of free radicals induced by THC

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.

Aim: To examine prospectively over a period of 4 years the profile of cannabis dependence and the risk of specific dependence criteria in a community sample of adolescents. Methods: A representative community sample of 2446 young adults aged 14–24 years at baseline was followed up over a period of 4 years. Frequency of use measures and of criteria for DSM-IV dependence were assessed by standardized diagnostic interview measures (CIDI). To explore the nature of this association, frequency of use and concomitant use of other psychoactive substances was considered. Results: 30% of the sample were cannabis users. Among all users 35% met at least one dependence criterion. Most frequently reported dependence criteria among all users were withdrawal (17%), tolerance (15%), loss of control (14%) and continued use despite a health problem (13%). Even without concomitant use of other illicit drugs, 22% of low frequency users and 81% of high frequency users met at least one dependence criterion. Symptom patterns were similar in high and low frequency users. The occurrence of a dependence syndrome or of specific dependence criteria could not be attributed to the use of other illicit drugs or to comorbid nicotine and alcohol dependence. Conclusions: Regular cannabis use in adolescence is associated with the development of a dependence syndrome. This association cannot be explained by the concomitant use of other illicit substances or by comorbid nicotine and alcohol dependence.

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.

Syftet med den föreliggande studien är att undersöka bevekelsegrunder till att ungdomaranvänder cannabis och vad användningen av cannabis i ung ålder kan få för effekter påungdomarnas psykosociala hälsa och utveckling. Syftet är även att undersöka på vilket sätt enlegalisering eller avkriminalisering av icke-medicinsk cannabis påverkar ungdomarsanvändning av, och inställning till, cannabis i de länder/stater där legalisering har genomförts.Studien har tre ledande frågeställningar: (1) att undersöka vilka faktorer som är särskiltframträdande för att motivera ungdomar att använda respektive avstå från cannabis, (2) attkartlägga vilka framträdande positiva- och negativa effekter cannabisanvändning i tidig ålderhar – i termer av psykosocial hälsa och utveckling, samt slutligen (3) undersöka ifall det finnsnågra skillnader i ungdomars cannabisanvändning samt inställning till cannabis innan,respektive efter, genomförandet av en legalisering/avkriminalisering – och på vilket sätt dessaskillnader i så fall kan förklaras. Studien har utformats som en integrativ litteraturöversikt ivilken både kvalitativa- och kvantitativa data har inkluderats för att besvara studiens syfte ochfrågeställningar. I resultatet blottläggs ett flertal bevekelsegrunder till att ungdomar använder,eller avstår från, cannabis. Dessa bevekelsegrunder kan summeras i tre övergripande teman:Avkoppling, tidsfördriv eller umgänge, omgivningens inställningar till cannabis samtsjälvmedicinering för välbefinnande. Resultatet visar att användningen av cannabis i ung ålderkan relateras till flera effekter för ungdomens psykosociala hälsa och utveckling, såsom psykiskohälsa i form av depression, självmordstankar, en högre risk att utveckla psykosliknandetillstånd och svårigheter att klara av skolan. Användningen kan samtidigt upplevas lindrandeav psykisk problematik och självskadebeteende samt leda till ökad kreativitet och medvetenhet.Därutöver visar resultatet att en legalisering och avkriminalisering av cannabis irekreationssyfte inte har någon signifikant påverkan på ungdomars användning av cannabis påkort sikt. Däremot finns ett samband mellan amerikanska legaliseringslagar för cannabis ochökande antal cannabisrelaterade sjukhusinläggningar bland ungdomar i flera amerikanskadelstater, speciellt i stater med legalisering av icke-medicinsk cannabis, vilket tyder på enförändring i ungdomars cannabisvanor. Vidare påvisar resultatet att legaliseringen, i deamerikanska stater där en legalisering genomförts, har bidragit till en ökad exponering förcannabisreklam i form av reklamannonser och skyltar vilket bidragit till en normalisering avcannabis. Slutligen diskuteras och analyseras studiens resultat utifrån studiens centrala begrepp,tidigare forskning och studiens teoretiska ramverk. / The following study aims to investigate the motives for adolescent cannabis use and in whatway cannabis use at a young age can affect the psychosocial health and development. Inaddition, the study intends to investigate in what way a legalization or decriminalization of nonmedicalcannabis affects young people's use of, and attitude towards, cannabis in the countries/ states where legalization has been implemented. The study has the major focal points: (1) toexamine which factors are prominent in motivating adolescents to use, or abstain, fromcannabis, (2) to identify the prominent positive and negative effects of cannabis use at an earlyage – in terms of psychosocial health and development, (3) to examine whether there are anydifferences in adolescent cannabis use and attitudes towards cannabis before, or after, theimplementation of a legalization/decriminalization – and in what way these differences can beexplained. The study is designed as an integrative literature review in which both qualitativeand quantitative data have been included to answer the study’s purpose and questions. Theresult of the study shows several factors who are prominent in motivating adolescent cannabisuse, such as recreational purposes, the attitudes of the social environment and self-medicationfor well-being. The results shows that the use of cannabis at a young age can be related toseveral psychosocial effects such as depression, suicidal thoughts, a higher risk of developingpsychosis-like conditions and school dropouts. The use of cannabis can also alleviate mentalproblems and self-harming behaviour and lead to increased creativity and awareness. Inaddition, the results show that the legalization and decriminalization of cannabis for recreationalpurposes has no significant impact on adolescent cannabis use in the short term. However, thereis a link between US cannabis legalization laws and the growing number of cannabis-relatedhospitalizations among adolescents in several US states, especially in states with legalizationof non-medical cannabis, indicating a change in adolescents' cannabis habits. Furthermore, theresults show that the legalization, in the US states where a legalization has been carried out, hascontributed to an increased exposure to cannabis advertising, which has contributed to anormalization of cannabis use. Finally, the results of the study are discussed and analysed basedon the key concepts, previous research, and the theoretical framework of the study.

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.

No description available.

Thèse présentée en vue de l’obtention du grade de Philosophiae Doctor (Ph.D.) en psychologie, option Recherche / Le cannabis est l’une des substances psychoactives les plus consommées par les jeunes de 21 à 24 ans au Québec, avec plus de 40 % rapportant avoir consommé au cours de la dernière année. Les jeunes de la diversité sexuelle et de genre (JDSG; c.-à-d. qui ne s’identifient pas comme exclusivement hétérosexuel·les et/ou ayant un genre qui ne s’aligne pas avec leur sexe assigné à la naissance) rapportent des niveaux encore plus élevés de consommation de cannabis (CC). Tandis que la plupart de la CC n’engendre pas de conséquence négative, les JDSG rapportent aussi des taux plus élevés de problèmes de CC que leurs pair·es hétérosexuel·les et cisgenres (c.-à-d. pour lesquel·les le genre et le sexe assigné à la naissance s’alignent). En même temps, les JDSG rapportent aussi plus de marginalisation, de stigmatisation et d’obstacles au bien-être. Par conséquent, ce groupe rapporte également plus de défis en santé mentale, qui sont associés à plus de CC et à plus de problèmes de CC. Il y a en effet une association particulièrement prononcée entre la CC et la santé mentale chez les JDSG. Toutefois, cette spécificité par rapport aux JDSG ainsi que les mécanismes explicatifs et les éléments contextuels pertinents restent à élucider. Une meilleure compréhension de ces associations est une étape clé vers une meilleure équité en matière de santé quant aux problèmes de CC et aux défis en santé mentale. L’objectif principal de cette thèse était donc de mieux comprendre les associations entre la CC, les problèmes de CC et la santé mentale chez les JDSG. Une approche séquentielle par méthodes mixtes a été abordée, cherchant dans un premier temps à fournir des pistes d’observation issues du volet qualitatif à ensuite examiner dans des études quantitatives. Le premier objectif spécifique était donc d’explorer de manière qualitative et communautaire le rôle de la CC dans la santé mentale des JDSG, prêtant une attention particulière aux distinctions et aux similarités entre les jeunes de ces communautés et les jeunes hétérosexuel·les et cisgenres. Le second objectif spécifique était d’examiner quantitativement les facteurs contextuels et les mécanismes explicatifs de l’association entre la CC, en particulier les problèmes de CC, et la santé mentale chez les JDSG. Afin de répondre au premier objectif, la première étude a utilisé une approche participative communautaire pour mener 27 entrevues qualitatives avec des JDSG au Québec. Cette analyse basée sur les forces de ces jeunes a montré comment la CC pouvait jouer plusieurs rôles dans le développement de l’identité et de la communauté, ainsi que dans la réponse à l’adversité. Les résultats ont aussi souligné plusieurs raisons pour lesquelles les JDSG consomment du cannabis, ainsi que la multitude de connexions existant entre la CC, les problèmes de CC, la santé mentale, les traumatismes, le stress, le soutien social et la neurodiversité. Ces résultats ont guidé l’approche et les analyses des deux articles quantitatifs. La deuxième étude s’est donc penchée sur les motifs de CC ainsi que sur les différences entre les jeunes de la diversité sexuelle et les jeunes hétérosexuel·les. Cette étude a examiné les associations longitudinales entre les symptômes de dépression et d’anxiété à l’adolescence et les motifs, la fréquence et les problèmes de CC en début d’âge adulte. Les symptômes de dépression à l’adolescence prédisaient les problèmes de CC que chez les jeunes de la diversité sexuelle. La consommation pour pallier des difficultés expliquait ce lien. La troisième étude a identifié des profils de CC auprès d’une plus petite cohorte ayant des mesures de CC détaillées. Les jeunes de la diversité sexuelle étaient plus susceptibles de faire partie du profil de CC le plus risqué, mais cette association était complètement expliquée par les niveaux plus élevés de stress dans ce groupe. Ensemble, ces résultats soutiennent la variété d’associations existant entre la CC et la santé mentale chez les JDSG. Ils soutiennent en particulier comment ces liens pourraient se distinguer entre les problèmes de CC, étant associés au stress, à la dépression et à la consommation pour palier des difficultés, tandis que la CC de manière plus générale pourrait appuyer non seulement la santé mentale, mais aussi le développement de l’identité et de la communauté, les réponses à l’adversité et la consommation sociale. Il en découle que la CC et les problèmes de CC peuvent être associés à la détresse que vivent ces jeunes, mais aussi que la CC peut être impliquée dans des expériences de santé mentale plus positives. / Cannabis is one of the most used psychoactive substances by young adults aged 21 to 24 years in Québec, with over 40% reporting past-year use. Levels of cannabis use (CU) are consistently higher among sexually and gender diverse youth (SGDY; i.e., whose sexual orientation is not exclusively heterosexual and/or whose gender does not align with their sex assigned at birth). While most CU does not produce negative consequences, SGDY also report higher rates of CU problems than their heterosexual and cisgender peers (i.e., whose gender aligns with their sex assigned at birth). At the same time, SGDY also report higher levels of marginalization, stigma and barriers to mental wellness. As a result, this group reports more mental health challenges, which have been linked to elevated rates of CU and CU problems. In fact, there seems to be a particularly strong association between CU and mental health among SGDY. However, it remains unclear why this is the case specifically among SGDY, and which mechanisms and contextual factors may play a key explanatory role. Better understanding these associations is a crucial step toward better health equity for both CU problems and mental health challenges. The overall objective of this thesis was thus to better understand the associations between CU, CU problems, and mental health among SGDY. A sequential, mixed methods approach was used, first generating qualitative insights, then examining these quantitatively. The first specific objective was to use community-based methods to qualitatively explore the role of CU in SGDY’s mental health, awarding particular attention to the ways that CU could fulfill needs that are distinct from or similar to those of cisgender and heterosexual youth. The second specific objective was to quantitatively examine potential key contextual factors and explanatory mechanisms in the association between CU, particularly CU problems, and mental health among SGDY. To fulfill the first objective, study one used a community-based approach to conduct qualitative interviews with 27 SGDY living in Québec. This strengths-based analysis provided insight into how CU could play various roles in supporting identity development, building community, and facing adversity. These findings also highlighted the wide array of reasons for which SGDY used cannabis, as well as the multitude of connections that existed between CU, CU problems, mental health, trauma, stress, social support, and neurodiversity. These findings in turn informed and guided the two quantitative studies in this thesis. As such, study two centred on CU motives, including potential differences between sexually diverse and heterosexual groups. This study longitudinally examined associations between symptoms of depression and anxiety in adolescence, and CU motives and CU outcomes in early adulthood. Symptoms of depression in adolescence were only a significant predictor of later CU problems among the sexually diverse group. This association was fully explained through coping motives for CU. Study three used a smaller cohort with detailed CU measures to identify profiles of CU. Sexually diverse participants were more likely to be part of the riskiest CU profile, but this association was fully explained through higher stress levels in this group. Together, these findings provide insight into a wide array of associations between CU and mental health among SGDY. Crucially, they illuminate how associations may differ between CU problems, which were specifically linked with stress, depression, and coping motives, and CU more broadly, which could also support mental health, but was additionally associated with identity, community, facing adversity, and social motives among SGDY. As such, while CU and CU problems may be prominently associated with distress among these youth, it is important not to overlook how CU may also play a role in positive mental health.

The aim of this thesis is to study how cannabis is constructed in contemporary Sweden, which policy responses are promoted as rational, and how international cannabis trends are received in this context. The four papers are the result of analyzing empirical material from three different sub-studies: 1) a qualitative study of online discussions about cannabis and drug policy, 2) a qualitative and comparative study of print media articles from 2002 and 2012, and 3) a qualitative study of oral presentations from cannabis information symposia. All papers are based on a social constructionist approach. A point of departure is that attitudes and regulations on cannabis have changed in large parts of the Western world. In Sweden, however, strict prohibition of cannabis is still central in the national drug laws. Some of the main findings can thus be gathered in discussions on continuity and change. In Swedish online discussions, there seems to be a strong desire to change the national cannabis policy in line with international developments. This discussion propagates alternative views on cannabis, in which comparisons to alcohol become vital and more liberal cannabis policies become logical. These discussions are also characterized by continuity, as many arguments for liberal cannabis policies seem to be based on traditional social democratic values and prohibitionist “scaremongering” arguments. Continuity is also what seems to characterize traditional print media, where cannabis is generally portrayed as a potent and illegal drug producing social problems. However, this arena also shows signs of change, as the material from 2012 includes stories on cannabis as an economic asset as well as a recreational substance. Both traditional print media and cannabis information symposia focus on youth consumers, who are seen as particularly vulnerable to cannabis effects. Such constructions seem important for protecting prohibition from international influences and for a continuous discourse centered on the dangers of cannabis. It is concluded that cannabis appears to be able to represent almost anything. As such it can be “used” for any purpose to promote a whole set of ideas related to policy often based on what is considered as scientific evidence. Depending on the context, it thus seems possible that cannabis is medicinal, recreational, harmful, and addictive. If so, and if all of these constructions are in some way “real,” then it is suggested that cannabis necessitates a much more tailored and nuanced response than that which prohibition can offer.

The expression of C-X-C Chemokine Receptor 4 (CXCR4) has been correlated with increased metastatic potential of cancer cells. CXCR4 increases tumor malignancy by encouraging tumors cells to migrate to distal organs expressing its cognate ligand, CXCL12, facilitating metastasis. Thus, targeting the CXCR4/CXCL12 signaling axis provides a good strategy to inhibit the metastatic spread of tumor cells and slow cancer progression. Various studies suggest that cannabis may have anti-proliferative as well as anti-metastatic properties, though a biochemical mechanism describing how this occurs has yet to be discovered. Our lab has confirmed that agonist-bound CXCR4 and agonist-bound Cannabinoid Receptor 2 (CB2) can form heterodimers that play a role in decreasing cancer cell migration. Simultaneous treatment of the breast cancer cell line, MDA-MB-231 and the prostate cancer cell line PC-3, with CXCL12 and AM1241, a synthetic ligand for CB2, desensitizes the intrinsic cellular response to migrate toward areas of high CXCL12 concentration. Furthermore, through co-immunoprecipitation and proximity ligation assays (PLA), we have determined that there is increased interaction between the two receptors with co-stimulation of respective agonists, providing evidence for the therapeutic notion that treating tumors that endogenously secrete CXCL12 with exogenous ligands for the cannabinoid can induce dimerization. Moreover, when CXCR4 and CB2 were activated simultaneously with various agonists, decreases in migration were observed, confirming that the regulatory activity was receptor-based, not agonist-based. Finally, to determine whether simultaneously–treated, dimerized receptors inhibited activity of respective receptors, calcium mobilization assays to determine G-protein coupled receptor activation were employed. Results showed that transiently activated calcium levels were significantly lower in response to simultaneous treated cells when compared to cells treated with their individual ligands. Phosphorylation of ERK and AKT were abrogated in response to simultaneous stimulation indicating loss in downstream signaling. Therefore, we believe that the interaction of CB2 with CXCR4 may play a role in inhibiting the cells response to CXCL12, leading to a loss in metastatic potential of cells expressing these receptors.