Epidemiology of Cannabis

Section A Mental illness1 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 studyIntroductionMethods - Analysis plan- Statistical considerations- Data availability- Assessing causalityResults - National level- Regional level- State level- Substate level- Considerations of causality- Koch's postulates- Hills' causal algorithm- Brain disease pathways and mechanisms- Cannabis and mass violenceBrain - Endocannabinoid system in the brain- Dopamine- Other- Mitochondriology- Immunome- Genomic studies- Cannabinoid-opioid interactionsConclusionSection B Autistic spectrum disorder2 Linked rise of cannabis use and autism incidence demonstrated by close three-level geospatiotemporal relationships, USA, 1990-2011IntroductionMethodological comment - Assessing causality- Data availabilityResults - National level data- Regional level- State level data- Impact of cannabis legal status on autism rates- Causal inferenceDiscussion - Mechanistic considerations- European neuroteratology studies- Morphogen gradients guide brain development- Retinoic acid- Slit-Robo- Neurexin-neuroligin- DSCAM and DLGAP2- Oligodendrocytes and myelination- Genomic studies- Epigenomic studies- Pediatric poisoningsConclusionGeneral questionsCase studies - Case 1- Case 2- Case 3Section C Congenital anomalies3 Geospatiotemporal and causal inferential analysis of United States congenital anomalies as a function of multiple cannabinoidand substance-exposures: Phenocopying thalidomide and hundred megabase-scale genotoxicityExecutive summary - Introduction- Methods- Ethics- Results- Cannabis-related defects- Upper quintile threshold discontinuityConclusionCannabis-related congenital anomalies - Cannabis-related anomalies by geotemporospatial criteria, N=38- Cannabis-related anomalies by prevalence ratio criteria, N=44- Cannabis-related anomalies by prevalence ratio criteria, N=42Introduction - Methodology- Data sources- Cannabis consumption quintiles- Data analysis- Statistics- Broom-Purrr multimodel assessments- Matrix multiplication- Geospatial modeling- Two phases of data analysis- Spatial error structures- Spatial model specification- Corrections for multiple testing- Assessing causality- Data availability- EthicsResults - Section one: Drug use by ethnicity and age- Section two: Drugs and congenital anomalies overview- Section three: Chromosomal defects- Section four: Gastroschisis and body wall- Section five: Atrial septal defect (secundum type)- Section six: Cardiovascular defects of interest- Section seven: Hawaiian-American reviewDiscussion - General considerations- Bivariate analysisSummary observations - Data summary- Forest plot- Canada- Australia- Mechanistic summary- Multivariable analysis- Multivariable causal analysis- Multivariable causal analysis- Effect of cannabis legalization- Considerations of causality- Geotemporal trimodality- Causality and the hill criteria- Causal inference- Causal assignment- CommonalityPathways and mechanisms - Genotoxic mechanisms- Morphogen gradients control body formation and patterning- Cannabinoid modulation of other morphogenetic pathwaysSpecific organ systems - Heart- Respiratory defects- Face- Gastrointestinal tract- Urinary tract- Body wall anomalies- Limbs- Chromosomal defectsInteractions of other major morphogen systems with cannabinoids - Cannabinoid teratology- Chromosomal mechanics and dynamics- Sperm and cannabinoids- Oocytes and cannabinoids- Embryonic developmentConclusion - Directions for future researchCongenital anomalies general questions and case studies - General questions- Case studies-- Case 1: Jodie-- Case 2: JenniferSection D Cancer and Heritable Cancer4 Geospatiotemporal and causal inferential epidemiological survey and exploration of cannabinoidand substance-related carcinogenesis in the United States from 2003 to 2017 (Online chapter)Secti