This research seeks to unravel the definition of sexual addiction amongst adolescents from the perspectives of professional social workers, working with these types of issues. This has been conducted through a qualitative study based on semi-structured interviews with social workers in various youth clinics in Stockholm. The results gathered from the interviews are presented and then analyzed through discourse analysis using the social constructionism as our theoretical framework. The primary results gathered, conclude that sexual addiction amongst adolescents is to be defined within the personal contact between the client and the social worker in order to build an individual case discourse. The results also depicts that shame and anxiety are the driving forces for the phenomenon. Furthermore, inconsistency was discovered regarding the terminology of the phenomenon amongst the social workers. It is important to note that the adolescent years are time of rapid change and, thus, the behavior resembling sexual addiction may not be permanent. The results are then discussed and compared to previous research.

Background: Cannabis use is highly prevalent among adolescents in Germany, and chronic cannabis use (CCU) during this developmental stage raises significant public health concerns due to its potential impact on neurodevelopment. Adolescents with CCU are at a major risk of developing Cannabis use Disorder (CUD), particularly when co-occurring psychiatric disorders are present, which can negatively affect treatment outcomes for CUD. Among these co-occurring disorders, psychotic and depressive disorders have frequently been associated with adolescent CCU. Moreover, CCU in adolescence is associated with cognitive impairment, with impaired verbal learning ability being a common manifestation. These cognitive impairments and co-occurring disorders are rooted in underlying neurobiological alterations that may disrupt normal brain development during adolescence. The psychoactive effects of cannabis primarily stem from Δ⁹-trans-Tetrahydrocannabinol, and it is suspected that cannabis use affects the signaling of the endocannabinoid system (ECS). The ECS, known for its regulatory role in various physiological systems such as stress and immune responses, has been implicated in the neurobiological processes underlying certain psychiatric disorders. In recent years, there has been a growing interest in understanding the factors contributing to neurobiological changes associated with psychiatric disorders. Epigenetic processes, which describe the interplay between environmental factors and genetic regulation of phenotypic expression, have gained particular attention. DNA methylation (DNAm), the most extensively studied epigenetic mechanism, has emerged as a central focus in identifying epigenetic changes that underlie the neurobiological processes involved in psychiatric disorders. The present dissertation aims to investigate the psychological, neurobiological, and epigenetic correlates associated with CCU in adolescent outpatients with CUD. By exploring these dimensions, this work seeks to enhance our understanding of the multifaceted factors contributing to CCU and its impact on adolescent mental health. Methods: This thesis consists of five studies presented in chapters 2 to 6. Chapter 2 provides a description of the sample of adolescent outpatients who sought treatment at the SUD outpatient center. The chapter focuses on the prevalence of cannabis and other substance use, the occurrence of cannabis and other substance use disorders (SUDs), and the presence of co-occurring psychiatric disorders. In chapter 3, a study examines the association between cannabis use, additional 3,4-methylenedioxymethamphetamine (MDMA) use and attenuated psychotic symptoms (APS). Chapter 4 presents a study that investigates the relationship between CCU and DNAm. Additionally, it explores the potential mediating effects of DNAm on the association between CCU and impaired cognitive performance. The focus of chapter 5 is on the relationship between depressive symptoms and DNAm in target genes related to depression. The study also examines the association between DNAm of depression-related genes and CCU, while exploring the mediating effects of DNAm on the relationship between CCU and depressive symptoms. Finally, in chapter 6, a study analyzes site-specific DNAm to estimate the proportions of circulating white blood cell types in adolescents with CCU compared to non-using controls (NCU). The study also investigates the DNAm profiles of selected immune cell markers and determines their gene expression levels. Results: In a first step, the prevalence of cannabis use and CUD among treatment seeking adolescents with suspected SUD was examined. Cannabis use and CUD was highly prevalent in the sample. The results indicated no effects of gender or age on cannabis use and CUD prevalence rates. Further, co-occurring conduct disorders, attention deficit hyperactivity disorders and depressive disorder were also highly prevalent in this sample. In chapter 3, the results did not indicate a relationship between APS and cannabis use, which was contrary to the predictions. MDMA use additional to cannabis however was associated with increased APS. However, as described in Chapter 4, CCU was associated with impairment in a verbal learning task. Furthermore, six CpG sites were identified whose DNAm levels showed a significant mediating effect on the relationship between CCU and verbal learning impairment. The results presented in Chapter 5 indicate that CCU is associated with increased depressive symptoms, and both depressive symptoms and CCU are associated with DNAm of one key gene in the stress system. Moreover, the findings in the last chapter, Chapter 6, suggest that CCU has immune-modulatory effects and affects the proportion of B-cells in adolescents with CCU, potentially acting through the alteration of DNAm of related genes. Discussion: The studies conducted in this thesis have produced several significant findings. Firstly, it was observed that cannabis use and CUD are highly prevalent among adolescents with SUDs. While there was no cross-sectional association between cannabis use and increased APS, it was associated with higher levels of depressive symptoms, poorer performance in verbal learning tasks, and a higher prevalence of co-occurring psychiatric disorders. Additionally, it was found that adolescent CCU may have an impact on the epigenome through alterations in DNAm. Specifically, these alterations may affect the regulation of cognitive processes by influencing neurogenerative processes. Adolescent CCU may also interfere with the stress axis through DNAm-related changes. Furthermore, there is evidence to suggest that adolescent CCU may impair parts of the immune system. However, it is important to note that the studies presented in this thesis are based on cross-sectional data, and therefore, causal interpretations cannot be made. The relationships discussed, which imply causality, are speculative and require examination in longitudinal studies.:Statement for a publication-based dissertation List of Tables List of Figures Important Abbreviations Abstract 1. General Introduction 1.1 Prevalence of Cannabis Use and Cannabis Use Disorder (CUD) 1.2 CCU associated cognitive and behavioral changes 1.3 Neurobiological changes associated with CCU in adolescence 1.4. Epigenetic regulations and DNA methylation 1.5 Research Aims and Hypotheses 1.6 Sample Population and Measurements 2. Prevalence of cannabis use and CUD in an outpatient clinic 2.1 Background 2.2 Methods 2.3 Results 2.4 Discussion 2.5 Conclusion 2.6 Acknowledgements, Funding, Conflicts of Interest 3. Cannabis use and psychotic symptoms 3.1 Background 3.2 Methods 3.3 Results 3.4 Discussion 3.5 Conclusion 3.6 Acknowledgements, Funding, Conflicts of Interest 4. CCU, cognitive impairment and shared epigenetic associations 4.1 Background 4.2 Methods 4.3 Results 4.4 Discussion 4.5 Conclusion 4.6 Acknowledgements, Funding, Conflicts of Interest 5. CCU, depressive symptoms and shared epigenetic associations 5.1 Background 5.2 Methods 5.3 Results 5.4 Discussion 5.5 Conclusion 5.6 Acknowledgements, Funding, Conflicts of Interest 6. Immunological alterations associated with CCU 6.1 Background 6.2 Methods 6.3 Results 6.4 Discussion 6.5 Conclusion 6.6 Acknowledgements, Funding, Conflicts of Interest 7. General Discussion 7.1 Summary 7.2. Implications for DNAm mediated disruption of cognitive systems due to adolescent CCU 7.3 Implications for DNAm mediated disruption of immunological systems and its interactions with depression in chronic cannabis users 7.4 Neurobiological and epigenetic alteration may be affected by CCU 7.5. Clinical Implications 7.6. Limitations & Future Research 8. References 9. Appendices 9.1 Appendix A (chapter 2) 9.2 Appendix B (chapter 3) 9.3 Appendix C (chapter 4) 9.4 Appendix D (chapter 5) 9.5 Appendix E (chapter 6) 10. Erklärung gemäß der Promotionsordnung