Epidemiology of Cannabis

<p>Section A Mental illness<br>1 Close parallels between cannabis use and deteriorating US Mental Health at four levels supports and extends the epidemiological salience of demonstrated causal mental health relationships: A geospatiotemporal study<br>Introduction<br>Methods</p>- Analysis plan<br>- Statistical considerations<br>- Data availability<br>- Assessing causality<p>Results</p>- National level<br>- Regional level<br>- State level<br>- Substate level<br>- Considerations of causality<br>- Koch&rsquo;s postulates<br>- Hills&rsquo; causal algorithm<br>- Brain disease pathways and mechanisms<br>- Cannabis and mass violence<p>Brain</p>- Endocannabinoid system in the brain<br>- Dopamine<br>- Other<br>- Mitochondriology<br>- Immunome<br>- Genomic studies<br>- Cannabinoid-opioid interactions<p>Conclusion<br><br><br>Section B Autistic spectrum disorder<br>2 Linked rise of cannabis use and autism incidence demonstrated by close three-level geospatiotemporal relationships, USA, 1990–2011<br>Introduction<br>Methodological comment</p>- Assessing causality<br>- Data availability<p>Results</p>- National level data<br>- Regional level<br>- State level data<br>- Impact of cannabis legal status on autism rates<br>- Causal inference<p>Discussion</p>- Mechanistic considerations<br>- European neuroteratology studies<br>- Morphogen gradients guide brain development<br>- Retinoic acid<br>- Slit-Robo<br>- Neurexin-neuroligin<br>- DSCAM and DLGAP2<br>- Oligodendrocytes and myelination<br>- Genomic studies<br>- Epigenomic studies<br>- Pediatric poisonings<p>Conclusion<br>General questions<br>Case studies</p>- Case 1<br>- Case 2<br>- Case 3<p><br>Section C Congenital anomalies<br>3 Geospatiotemporal and causal inferential analysis of United States congenital anomalies as a function of multiple cannabinoidand substance-exposures: Phenocopying thalidomide and hundred megabase-scale genotoxicity<br>Executive summary</p>- Introduction<br>- Methods<br>- Ethics<br>- Results<br>- Cannabis-related defects<br>- Upper quintile threshold discontinuity<p>Conclusion<br>Cannabis-related congenital anomalies</p>- Cannabis-related anomalies by geotemporospatial criteria, N=38<br>- Cannabis-related anomalies by prevalence ratio criteria, N=44<br>- Cannabis-related anomalies by prevalence ratio criteria, N=42<p>Introduction</p>- Methodology<br>- Data sources<br>- Cannabis consumption quintiles<br>- Data analysis<br>- Statistics<br>- Broom-Purrr multimodel assessments<br>- Matrix multiplication<br>- Geospatial modeling<br>- Two phases of data analysis<br>- Spatial error structures<br>- Spatial model specification<br>- Corrections for multiple testing<br>- Assessing causality<br>- Data availability<br>- Ethics<p>Results</p>- Section one: Drug use by ethnicity and age<br>- Section two: Drugs and congenital anomalies overview<br>- Section three: Chromosomal defects<br>- Section four: Gastroschisis and body wall<br>- Section five: Atrial septal defect (secundum type)<br>- Section six: Cardiovascular defects of interest<br>- Section seven: Hawaiian—American review<p>Discussion</p>- General considerations<br>- Bivariate analysis<p>Summary observations</p>- Data summary<br>- Forest plot<br>- Canada<br>- Australia<br>- Mechanistic summary<br>- Multivariable analysis<br>- Multivariable causal analysis<br>- Multivariable causal analysis<br>- Effect of cannabis legalization<br>- Considerations of causality<br>- Geotemporal trimodality<br>- Causality and the hill criteria<br>- Causal inference<br>- Causal assignment<br>- Commonality<p>Pathways and mechanisms</p>- Genotoxic mechanisms<br>- Morphogen gradients control body formation and patterning<br>- Cannabinoid modulation of other morphogenetic pathways<p>Specific organ systems</p>- Heart<br>- Respiratory defects<br>- Face<br>- Gastrointestinal tract<br>- Urinary tract<br>- Body wall anomalies<br>- Limbs<br>- Chromosomal defects<p>Interactions of other major morphogen systems with cannabinoids</p>- Cannabinoid teratology<br>- Chromosomal mechanics and dynamics<br>- Sperm and cannabinoids<br>- Oocytes and cannabinoids<br>- Embryonic development<p>Conclusion</p>- Directions for future research<p>Congenital anomalies general questions and case studies</p>- General questions<br>- Case studies<br>-- Case 1: Jodie<br>-- Case 2: Jennifer<p><br>Section D Cancer and Heritable Cancer<br>4 Geospatiotemporal and causal inferential epidemiological survey and exploration of cannabinoidand substance-related carcinogenesis in the United States from 2003 to 2017 (Online chapter)<br><br><br>Section E Epigenetics and aging<br>5 Multivalent cannabinoid epigenotoxicities and multigenerational aging<br>Introduction<br>Definitions<br>Epigenetic layers<br>Hallmarks of aging<br>Methodology</p>- Data<br>- Computations<br>- Ethical permission<p>Results and discussion</p>- Historical studies<br>- Mitochondrial inhibition<br>- Important earlier epigenomic studies<br>- Longitudinal human sperm study<br>- Detailed analysis of longitudinal sperm study results<br>- Perturbation of fundamental epigenomic machinery<br>- Stem cell genes<br>- Age-related immunometabolic genes<br>- Chromosomes, centrosomes, and kinetochores<br>- DNA repair<br>- Epigenomics<p>Epigenomics of cannabinoid teratology</p>- Brain<br>- Cannabinoid neurotoxicity<br>- Cannabinoid epigenomic neurotoxicity<br>- Summary of cannabinoid neurotoxicity<br>- Cardiovascular system<br>- Other organs and systems<br>- Chromosomal anomalies<br>- Uronephrology<br>- Body wall<br>- Teratological summary<p>Epigenomics of cannabinoid-related cancers<br>Epigenomics of aging</p>- Overview of conceptual aging paradigm<br>- Aging is driven by a loss of epigenetic information<br>- Epigenomics<br>- Overall pattern of cannabis toxicity<br>- Hallmarks of cannabinoid accelerated aging<p>Epigenomic—genomic overlap in aging syndromes</p>- Heterochronic parabiosis<br>- Haemopoietic stem cells<br>- Heterochronic CSF circulation<br>- Movement in fibroblasts<br>- Ovarian aging<br>- Mouse aging<p>Epigenomics and pathobiology of aging</p>- Inflammation and stem cells<br>- Cardiovascular disease<br>- Hematopoietic stem cells<br>- Skeletal muscle<br>- Summary genomic-epigenomic tables<br>- Summary of cannabinoid aging acceleration<p>Overall summary of multivalent cannabinoid epigenotoxicities<br>Case studies—Epigenetics and aging</p>- Leonard - Case description<br>- Case questions<br>- Q multiple choice<p><br>6 Conclusion</p>