The thesis is comprised of three separate studies that each relate to one of the aforementioned therapy types: complementary, alternative, and integrative medicine (CAIM), natural health products (NHPs), and medical cannabis. Parallels can be drawn across these therapy types in general including patient preference and prevalence of use, quality of patient health information, and safety and effectiveness concerns. Knowledge of these parallels both informed the development of these three studies and emerged across findings. Chapter 1 provides a comprehensive introduction to these parallels in the context of CAIM, NHPs, and medical cannabis. Chapter 2 comprises a cross-sectional survey determining NHP use disclosure to primary care physicians among patients attending a Canadian naturopathic clinic. Chapter 3 comprises a qualitative interview study identifying attitudes towards medical cannabis among family physicians practicing in Ontario, Canada. Chapter 4 comprises a sentiment analysis of Twitter data to understand how CAIM is mentioned during the COVID-19 pandemic. Lastly, chapter 5 serves as the conclusion of this thesis, and summarizes the most important findings, addresses study strengths and limitations, and discusses future directions from this work. / Thesis / Doctor of Philosophy (PhD)

Electronic nicotine delivery systems emerged during the 2010s as a novel way to consume (i.e., vape) nicotine. Public health authorities became concerned that vaping could cause nicotine-naïve youth to begin using tobacco products and that a new generation of youth could become tobacco-dependent. Though millions of youth have vaped, authorities' fears about a new generation of youth tobacco dependence has not materialized. A more recent concern is nicotine vaping’s potential effects on cannabis use and the use of other substances. An increase in cannabis use among some adolescent groups and young adults could be because of nicotine vaping’s rise. Additionally, cannabis can be vaped, so transitioning from nicotine vaping to cannabis vaping may be easier than transitioning from nicotine vaping to other forms of cannabis use. Furthermore, nicotine product use was historically associated with later use of cannabis and other substances; this trend may be renewed with the advent of nicotine vaping. To date, most studies on the associations between nicotine vaping and cannabis/other substance use are cross-sectional, so more longitudinal evidence is needed. If evidence suggests that nicotine vaping does affect the use of cannabis and other substances, specifying a mechanism would help with developing potential interventions and with testing the validity of total effects. The overarching goal of this dissertation is to advance evidence of nicotine vaping's potential harmful effects on youth and young adults, which could be used to support interventions aimed at reducing the burden of nicotine vaping's outcomes. First, I conducted a systematic review in which I examined the extent to which confounding, measurement errors, and loss to follow-up could alternatively explain reported longitudinal effects of nicotine vaping on cannabis use or other substance use. I also identified studies that tested effect modification and mediation. This systematic review revealed that nicotine vaping likely increases the risk of subsequent cannabis use and other substance use for up to 24 months. It also revealed that some studies evaluated effect measure modification, while no study assessed mechanisms. These observations suggest that future studies should assess long-term effects on initiation and evaluate potential mechanisms. Second, I evaluated whether nicotine vaping affected the initiation of cannabis and other substances over a six-year period among adolescents as they age into adulthood. Results suggested that nicotine vaping had harmful effects on both outcomes over the six-year period. I also found evidence that nicotine vaping's harmful effects in later years appeared stronger than in earlier years; the absence of age effects suggest the absence of cohort effects. Furthermore, I found that effects appeared stronger among individuals who had a history of non-vaping tobacco product use than among individuals without a history of non-vaping tobacco product use, suggesting that tobacco use is key to nicotine vaping's harms. Finally, I evaluated possible mechanisms of the effects based on a theory that I developed from prior empirical literature and behavioral theory. I posited that nicotine vaping caused deviant peer affiliation, which caused conduct problems and subsequently, the outcomes. I found no evidence that three conduct problems (considered together) were mechanisms of the effects. Future studies of mechanisms can reveal potential intervention targets, lead to studies of other potential mechanisms, and help test the validity of total effects. This dissertation achieved its goal of advancing evidence that nicotine vaping may harm youth and young adults. Public health bodies tasked with addressing potential public health concerns about nicotine vaping products should consider evidence from this dissertation.

Background: Marketing communication is the process of communicating with the customer, this is all communicative materials that are produced by the firm in order to influence the consumer. Regulations are all the rules, instructions, memos issued by a market authority that dictate the ways a firm may present their brand. Important to gain the firm's understanding of regulations and the ways to work within them. Purpose: The purpose of this paper is to explore how external regulations impact marketing communications from the firm's perspective. Research Question: How do companies understand the impact of regulations on marketing communications and work within them? Theoretical framework: The theoretical framework was established using the marketing communications mix in combination with institutional theory, investigating the research question through the lens of institutional pressures. Methodology: This study used a qualitative and inductive approach, using a case study on the Canadian cannabis industry. Using purposive sampling and semi-structured interviews with three respondents to collect data. Analysing the collected data with a systematic coding process to objectively interpret meaning from the respondents perspectives. Conclusion: The conclusions of this paper were threefold. First, coercive pressure is the most observed form of isomorphic pressure as there has not been enough industry maturity to establish normative pressures which leads to a hesitancy of mimetic behaviour. Secondly, there are multiple layers of institutional pressures from various dominant actors within the shared organisational environment, which leaves firms feeling incapable of marketing. Lastly, personal selling is the most effective tool from the marketing communication mix due to the impacts of the regulations and the infancy of the market.  Contribution: Study confirms the findings of Asquith’s (2021) research. Multiple layers of institutional pressure in the industry. Infant markets are more susceptible to coercive pressure.

Cannabis is widely consumed by humans for pharmacological effects that are mediated by THC, though there is little evidence that THC is a primary reinforcer in non-human animal models. We hypothesized that THC may have potent reinforcement enhancing effects, comparable to other drugs (e.g., nicotine and caffeine) which are also widely consumed by humans, but difficult to establish as primary reinforcers in non-humans. In three experiments with male and female rats saccharin (SACC) or a visual stimulus (VS) served as reinforcers for operant behavior. We explored several pharmacological parameters of THC on responding for SACC or VS, including THC dose, intervals between THC injections and testing, and intervals between test sessions. THC acts as a reinforcement enhancer for both SACC and a VS across a range of doses and intervals. Daily THC injections systematically reduced behavior, possibly due to accumulation of THC bioavailability.

Mammary gland (MG) is a dynamic organ that is essential for the production and secretion of breast milk. During pregnancy the MG undergoes a critical phase of remodeling, which is accompanied by the differentiation of mammary epithelial cells (MECs). During lactation, the MG requires high level of energy for proper folding of proteins in the secretory pathway, which takes place in the endoplasmic reticulum (ER). Limited evidence has been reported on the impact of cannabis or its components, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on the differentiation of MECs. However, both THC and CBD have been reported to induce ER stress in various cell types, resulting in impacting cellular function. Furthermore, consequences of cannabis use in the perinatal period on breast milk composition have not been reported. Using the HC11 cell line, we investigated whether THC and CBD evoke ER stress in MECs resulting in the impaired cellular function. We also reported on the effects of cannabis use during pregnancy and lactation on the levels of macronutrients and bioactive factors in the breast milk of cannabis users. Relative to control, 10μM THC and 10μM CBD reduced mRNA levels of milk proteins (CSN2 and WAP) and lipid synthesizing enzymes (FASN, FABP4, PLIN2 and LPL), as well as whey acidic protein and lipid levels. In addition, 10μM THC, 10μM CBD, and the combination of 10μM THC + 10μM CBD significantly induced the expression of ER stress genes in HC11 cells. Furthermore, in the milk of women who used cannabis during pregnancy and lactation, the levels of secretory immunoglobulin A (SIgA) were decreased, relative to non-users. Altogether, our findings indicate that cannabis use in the perinatal period may have implications on breast milk composition and infant health. / Thesis / Doctor of Philosophy (Medical Science) / Breast milk is crucial to the nutrition and immunity of the newborn. It is produced by the mammary gland (MG), which is composed of mammary epithelial cells (MEC) that play a key role in producing and secreting proteins and factors into the milk. During pregnancy, the MG undergoes remodeling which is accompanied by differentiation of the MECs (change from unspecialized to a specialized stage that allows the MECs to produce milk proteins and other factors). The disruption in MEC differentiation can result in altered milk production and composition. Cannabis is used by women during pregnancy and breastfeeding. In this study, we investigated the impact of cannabinoids on the MEC differentiation and examined the effect of cannabis use in the perinatal period on the breast milk composition in humans. We reported that cannabinoids reduced the differentiation of MECs and maternal cannabis use during breastfeeding reduced levels of an essential immune factor.

Background: Cannabis is the third most consumed drug worldwide. Thus, healthcare providers should be able to identify users who are in need for an intervention. This study aims to explore the relationship of acute, chronic, and early exposure (AE, CE, and EE) to cannabis with cognitive and behavioral harms (CBH), as a first step toward defining risky cannabis use criteria. Methods: Adults living in Spain who used cannabis at least once during the last year answered an online survey about cannabis use and health-related harms. Cannabis use was assessed in five dimensions: quantity on use days during the last 30 days (AE), frequency of use in the last month (AE), years of regular use (YRCU) (CE), age of first use (AOf) (EE), and age of onset of regular use (AOr) (EE). CBH indicators included validated instruments and custom-made items. Pearson correlations were calculated for continuous variables, and Student’s t-tests for independent samples were calculated for categorical variables. Effect sizes were calculated for each of the five dimensions of use (Cohen’s d or r Pearson correlation) and harm outcome. Classification and Regression Trees (CART) analyses were performed for those dependent variables (harms) significantly associated with at least two dimensions of cannabis use patterns. Lastly, logistic binary analyses were conducted for each harm outcome. Results: The mean age of participants was 26.2 years old [standard deviation (SD) 8.5]. Out of 2,124 respondents, 1,606 (75.6%) reported at least one harm outcome (mean 1.8 and SD 1.5). In our sample, using cannabis on 3 out of 4 days was associated with an 8-fold probability of scoring 4+ on the Severity Dependence Scale (OR 8.33, 95% CI 4.91–14.16, p < 0.001), which is indicative of a cannabis use disorder. Also, a start of regular cannabis use before the age of 25 combined with using cannabis at least once per month was associated with a higher probability of risky alcohol use (OR 1.33, 95% CI 1.12–1.57, p = 0.001). Besides, a start of regular cannabis use before the age of 18 combined with a period of regular use of at least 7.5 years was associated with a higher probability of reporting a motor vehicle accident (OR 1.81, 95% CI 1.41–2.32, p < 0.0001). Results were ambiguous regarding the role that age of first use and milligrams of THC per day of use might play regarding cannabis-related harms. Conclusions: The relationship among AE, CE, and EE with CBH indicators is a complex phenomenon that deserves further studies. The pattern of cannabis use should be carefully and widely evaluated—(not just including frequency but also other dimensions of pattern of use)—in research (preferably in longitudinal studies) to assess cannabis-related harms.

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Cannabis use may occur during pregnancy to alleviate symptoms of nausea, anxiety, and stress. However, fetal exposure to cannabinoids, such as THC and CBD, poses potential risks to neurodevelopment and long-term health outcomes. The endocannabinoid system (ECS) is involved in neurodevelopment and gastrointestinal (GI) homeostasis and responds to exogenous cannabinoids. This study aimed to investigate both the baseline development of the ECS in the GI tract and the effects of prenatal cannabis exposure on the development of gut-brain axis components and the ECS. Samples from outbred mice were collected at a set of developmentally important time points, ranging from embryonic day 14 to postnatal day 21. The localization of cannabinoid receptor 1 (CB1) expression was examined in the fetal and postnatal small intestine, and mRNA analysis was performed to evaluate changes in gene expression. Under normal conditions, components of the ECS display developmental regulation in the GI tract. A subset of pregnant mice was exposed to cannabis smoke daily, using a strain of cannabis containing high concentrations of THC, simulating ‘real world’ cannabis use. Exposure to cannabis prenatally revealed significant changes in biometric outcomes, and in the transcription of genes associated with the ECS, ENS development, barrier function, and serotonin signaling pathways. In addition, the onset of ambulation was delayed. These findings provide valuable insights into the developmental regulation of ECS during the prenatal period and highlight the potential risks associated with prenatal cannabis exposure, particularly in terms of gut-brain axis development. Further research is required to better understand the underlying mechanisms. / Thesis / Master of Science (MSc) / There have been growing reports of cannabis consumption during pregnancy, to relieve nausea, anxiety, and stress. However, compounds in cannabis, like THC and CBD, can pose risks to the baby's development and long-term health. This project studied how cannabis use during pregnancy affects gastrointestinal (GI) development, and communication between the GI system and the brain. The endocannabinoid system (ECS) plays a role in regulating the normal functioning of the GI tract and is influenced by cannabis compounds. By exposing pregnant mice to cannabis smoke, we observed significant changes in gene expression in the fetal intestine relating to the GI nervous system, the strength of the gut barrier, and various molecular signalling pathways. In addition, prenatally exposed mice had delayed walking ability. These findings highlight the potential risks of cannabis use during pregnancy on gut-brain axis development. Further research is needed to understand the mechanisms causing these disruptions.

Recently many States have legalised the production and retail of recreational cannabis, which is already a big business worldwide, and therefore, thoroughly attractive to international investors who would – reasonably – seek to develop their business in cannabis-friendly jurisdictions but, more so than many investments, this one carries with it a certain risk: Many influential and capital-exporting states are reticent to legalise cannabis for themselves and many times even criminalise any and all cannabis-related activities.  This work uses this dilema to explore the influence of the home-State of the investment on the legality of an investment, and question the uniletarality of the obligations derived from "Free Movement of Liquid Assets" or "repatriation" clauses, arguing that there is a multilateral obligation to protect the movement of investments' returns and that home-States to the investor must fulfill it by not impeding or upseting the repatriation of liquid assets.

Introduction : Le cannabis est une des substances psychotropes les plus utilisées à l’échelle mondiale et sa consommation peut être décrite sur un continuum, allant de l’usage récréatif jusqu’au trouble de l’usage. De ce fait, la recherche s’intéresse de plus en plus à des interventions efficaces, particulièrement pour la gestion du besoin impérieux de consommer une substance (ou craving). De nombreuses études ont en effet montré que le craving était très souvent associé à la consommation de substances, incluant le cannabis. L’activité physique (AP) est souvent mentionnée comme une stratégie potentielle de réhabilitation dans le cadre d’une consommation de substance. Parmi les concepts émergents dans le domaine de l’activité physique, on peut citer l’utilisation des affects. Un affect étant globalement une sensation de plaisir ou de déplaisir dont on pourrait se servir pour guider l’intensité de séances d’exercice physique dans le but de maximiser son appréciation. Enfin, récemment, un faisceau de preuves a suggéré que l’exercice physique pourrait stimuler les circuits de la récompense au niveau cérébral par l’intermédiaire du système endocannabinoïde. Objectifs : Dans ce contexte, nous souhaitions tester l’effet d’un programme d’entraînement physique, centré sur les affects, de 4 semaines sur la consommation de cannabis (en fréquence et en intensité) ainsi que le craving autorapportés chez 4 consommateurs récréatifs de cannabis. Nous souhaitions également étudier l’impact du programme d’entrainement sur les affects positifs et l’envie de manger/craving alimentaire des participants. Méthode : Nous avons réalisé une série de devis expérimentaux à cas unique de type A-B-A’ couplés à des mesures d’évaluations écologiques instantaneés par téléphone. Les critères de jugement principaux ont été mesurés avec une série d’items validés durant 3 notifications quotidiennes. Hypothèses : Nous pensions que la consommation de cannabis et le niveau de craving autorapportés allaient diminuer durant la phase d’entrainement (phase B) en comparaison à la phase A observationnelle. Nous nous attendions également à ce que l’intervention d’exercice physique soit bien acceptée par les participants et qu’elle soit associée à une amélioration des affects positifs ainsi qu’une réduction du craving alimentaire durant la phase B. Résultats : Un total de 504 mesures a été collecté. Pour le craving, deux de nos participants sur quatre ont montré une augmentation significative pendant la phase B. Un seul d’entre eux a montré une diminution significative du craving pendant la phase B. Pour la fréquence de consommation, deux participants sur quatre ont montré une augmentation significative pendant la phase B. Aucun n’a montré une diminution significative de sa fréquence de consommation pendant la phase B. Pour l’intensité de consommation, deux participants sur quatre ont montré une diminution significative pendant la phase B. Aucun n’a montré une augmentation de son intensité de consommation pendant la phase B. Concernant les affects positifs, nos résultats n’ont pas montré d’effets significatifs de notre intervention. Enfin, au niveau du craving alimentaire, seul un participant sur quatre a montré une diminution significative pendant la phase B. Discussion : Nos résultats ont confirmé l’aspect intra et interindividuel de l’AP, c’est-à-dire la grande variabilité des réponses pouvant être obtenues suite à l’AP chez un même, mais aussi chez différents individus. L’absence de patrons de réponses homogènes nous pousse à questionner l’effet bénéfique de ce type d’interventions en AP pour diminuer le craving et la consommation chez des consommateurs récréatifs de cannabis. Conclusion : Il semblerait donc que les interventions en AP centrées sur les affects ne soient pas forcément recommandées pour les consommateurs récréatifs de cannabis si ces derniers souhaitent diminuer leur craving ainsi que leur fréquence de consommation. En revanche, des effets très prometteurs ont été obtenus sur la réduction de l’intensité de consommation. D’autres interventions devraient être menées afin de mieux identifier à la fois les éléments intrinsèques à l’intervention qui mènent à une diminution du craving et de la consommation, mais aussi les caractéristiques des participants chez qui on peut voir des améliorations. / Introduction: Cannabis is one of the most widely used psychotropic substances worldwide and its use can be described on a continuum, ranging from recreational use to cannabis use disorder. As a result, research is increasingly interested in effective interventions, especially for craving management, an extreme urge to consume a substance. Numerous studies have indeed shown that craving is very often associated with consumption of substances, including cannabis. Physical activity (PA) is often mentioned as a potential rehabilitation strategy for substance use. Among the emerging concepts in the field of physical activity is the consideration of affect. An affect could be described as a feeling of pleasure or displeasure which could be used to guide the intensity of physical exercise sessions in order to maximize one's appreciation. Recently, a corpus of evidence has proposed that physical exercise may stimulate reward circuits in the brain via the endocannabinoid system. Objectives: We wanted to test the effect of a 4-week affect-centered training program on cannabis use (in frequency and intensity) as well as self-reported craving in 4 recreational cannabis users. We also wanted to study the impact of the training program on participants' positive affect and food cravings. Method: We carried out a series of single-case experimental studies (A-B-A’ type) coupled with ecological momentary assessment measures via mobile phone. The main judgment criteria were measured with validated items during 3 daily reports. Hypotheses: We thought that self-reported cannabis use and craving would decrease during the training program (B stage) compared to the observational stage (A stage). We also expected that the exercise program would be well accepted by the participants and that it would be associated with an improvement in positive affect as well as a reduction in food craving during B stage. Results: A total of 504 measures were collected. As for craving, two out of four of our participants showed a significant increase during B stage. Only one of them showed a significant decrease in craving during B stage. As for frequency of consumption, two out of four participants showed a significant increase during B stage. None showed a significant decrease in their frequency of consumption during B stage. As for consumption intensity, two out of four participants showed a significant decrease during B stage. None showed a significant increase in consumption intensity during B stage. Regarding positive affect, our results did not show any significant effects of our intervention. Finally, in terms of food craving, only one in four participants showed a significant decrease during B stage. Discussion: Our results confirmed the intra and interindividual aspect of PA, i.e. the great variability of responses that can be obtained following PA in the same person, but also in different individuals. The absence of homogeneous response patterns leads us to question the beneficial effect of this type of PA intervention in reducing craving and consumption in recreational cannabis users. Conclusion: It seems that affect-centered PA interventions are not necessarily recommended for recreational cannabis users if they wish to reduce cannabis craving and frequency of consumption. On the other hand, very promising effects have been obtained on the reduction of consumption intensity. Futures interventions should be carried out in order to better identify both the intrinsic aspects of the intervention that lead to a reduction in craving and consumption, but also characteristics of the participants in whom we can see improvements.