Epidemiology of Cannabis

Section A Mental illness
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
Introduction
Methods- Analysis plan
- Statistical considerations
- Data availability
- Assessing causality

Results- 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 violence

Brain- Endocannabinoid system in the brain
- Dopamine
- Other
- Mitochondriology
- Immunome
- Genomic studies
- Cannabinoid-opioid interactions

Conclusion

Section B Autistic spectrum disorder
2 Linked rise of cannabis use and autism incidence demonstrated by close three-level geospatiotemporal relationships, USA, 1990–2011
Introduction
Methodological comment- Assessing causality
- Data availability

Results- National level data
- Regional level
- State level data
- Impact of cannabis legal status on autism rates
- Causal inference

Discussion- 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 poisonings

Conclusion
General questions
Case studies- Case 1
- Case 2
- Case 3

Section C Congenital anomalies
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
Executive summary- Introduction
- Methods
- Ethics
- Results
- Cannabis-related defects
- Upper quintile threshold discontinuity

Conclusion
Cannabis-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=42

Introduction- 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
- Ethics

Results- 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 review

Discussion- General considerations
- Bivariate analysis

Summary 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
- Commonality

Pathways and mechanisms- Genotoxic mechanisms
- Morphogen gradients control body formation and patterning
- Cannabinoid modulation of other morphogenetic pathways

Specific organ systems- Heart
- Respiratory defects
- Face
- Gastrointestinal tract
- Urinary tract
- Body wall anomalies
- Limbs
- Chromosomal defects

Interactions of other major morphogen systems with cannabinoids- Cannabinoid teratology
- Chromosomal mechanics and dynamics
- Sperm and cannabinoids
- Oocytes and cannabinoids
- Embryonic development

Conclusion- Directions for future research

Congenital anomalies general questions and case studies- General questions
- Case studies
-- Case 1: Jodie
-- Case 2: Jennifer

Section D Cancer and Heritable Cancer
4 Geospatiotemporal and causal inferential epidemiological survey and exploration of cannabinoidand substance-related carcinogenesis in the United States from 2003 to 2017 (Online chapter)

Section E Epigenetics and aging
5 Multivalent cannabinoid epigenotoxicities and multigenerational aging
Introduction
Definitions
Epigenetic layers
Hallmarks of aging
Methodology- Data
- Computations
- Ethical permission

Results and discussion- Historical studies
- Mitochondrial inhibition
- Important earlier epigenomic studies
- Longitudinal human sperm study
- Detailed analysis of longitudinal sperm study results
- Perturbation of fundamental epigenomic machinery
- Stem cell genes
- Age-related immunometabolic genes
- Chromosomes, centrosomes, and kinetochores
- DNA repair
- Epigenomics

Epigenomics of cannabinoid teratology- Brain
- Cannabinoid neurotoxicity
- Cannabinoid epigenomic neurotoxicity
- Summary of cannabinoid neurotoxicity
- Cardiovascular system
- Other organs and systems
- Chromosomal anomalies
- Uronephrology
- Body wall
- Teratological summary

Epigenomics of cannabinoid-related cancers
Epigenomics of aging- Overview of conceptual aging paradigm
- Aging is driven by a loss of epigenetic information
- Epigenomics
- Overall pattern of cannabis toxicity
- Hallmarks of cannabinoid accelerated aging

Epigenomic—genomic overlap in aging syndromes- Heterochronic parabiosis
- Haemopoietic stem cells
- Heterochronic CSF circulation
- Movement in fibroblasts
- Ovarian aging
- Mouse aging

Epigenomics and pathobiology of aging- Inflammation and stem cells
- Cardiovascular disease
- Hematopoietic stem cells
- Skeletal muscle
- Summary genomic-epigenomic tables
- Summary of cannabinoid aging acceleration

Overall summary of multivalent cannabinoid epigenotoxicities
Case studies—Epigenetics and aging- Leonard - Case description
- Case questions
- Q multiple choice

6 Conclusion