Dr. Smith is very much to be congratulated for boldly speaking the truth about neuropsychiatric complications of cannabis. However the concerns about cannabis neurotoxicity extend beyond mental illness seen in youth and adults as cannabis has been shown to be linked with autism spectrum disorder developing in children [1 2]. Furthermore based on US data the leading addiction researcher in the world has also linked cannabis with suicide [3].
Cannabis has also been linked with many birth defects in USA and Europe [4 5].
Cannabis has also been linked with many cancers in USA and Europe [6 7].
Cannabis has also been linked with aging based on the acceleration of 20 metrics of aging [8 9].
Cannabis and cannabinoids are widely agreed to be genotoxic. This includes warnings from the industry and warnings from regulators. As the genotoxic moiety has been shown to reside in the olivetol nucleus on the C-ring 10 this genotoxic effect can be assumed to be a general class effect applying to all the cannabinoids. This view is supported by the above cited epidemiological studies.
Many studies show that the toxic effects of cannabinoids on the epigenome and metabolome are both exponential – implying that as the prevalence of use, the intensity of daily use and the potency of cannabis products rises a “switch-like” effect of high dose cannabinoid exposure will kick in and once rare effects will become commonplace – as is indeed presently occurring.
Together this now impressive body of evidence indicates that cannabinoid genotoxicity is much more common and far more impactful than is generally realized. As the use of cannabis continues to grow the incidence of these deleterious genotoxic effects will continue to rise. Since genotoxicity and epigenotoxicity is inheritable for many generations drug policies of today will impact several generations to come.
Like an iceberg much of this is presently lying below the waterline of common public health consideration. If we are to charge unknowingly and unadvisedly into a sea of icebergs as did the captain of the Titanic our communities will likely share their fate.
References
1. Reece A.S., Hulse G.K. Impact of Converging Sociocultural and Substance-Related Trends on US Autism Rates: Combined Geospatiotemporal and Causal Inferential Analysis. European archives of psychiatry and clinical neuroscience 2022;19(13):7726-52. doi: 10.1007/s00406-022-01446-0
2. Schrott R, Acharya K, Itchon-Ramos N, et al. Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm. Epigenetics 2020;15(1-2):161-73. doi: 10.1080/15592294.2019.1656158 [published Online First: 2019/08/28]
3. Han B, Compton WM, Einstein EB, et al. Associations of Suicidality Trends With Cannabis Use as a Function of Sex and Depression Status. JAMA Netw Open 2021;4(6):e2113025. doi: 10.1001/jamanetworkopen.2021.13025 [published Online First: 20210601]
4. Reece AS, Hulse GK. Geotemporospatial and causal inference epidemiological analysis of US survey and overview of cannabis, cannabidiol and cannabinoid genotoxicity in relation to congenital anomalies 2001–2015. BMC Pediatrics 2022;22(1):47-124. doi: 10.1186/s12887-021-02996-3
5. Reece A.S., Hulse G.K. Cannabinoid- and Substance- Relationships of European Congenital Anomaly Patterns: A Space-Time Panel Regression and Causal Inferential Study. Environmental Epigenetics 2022;8(1):1-40.
6. Reece A.S., Hulse G.K. Geotemporospatial and Causal Inferential Epidemiological Overview and Survey of USA Cannabis, Cannabidiol and Cannabinoid Genotoxicity Expressed in Cancer Incidence 2003–2017: Part 1 – Continuous Bivariate Analysis. Archives of Public Health 2022;80:99-133. doi: doi.org/10.1186/s13690-022-00811-8
7. Reece A.S., Hulse G.K. Cannabis Genotoxicity and Cancer Incidence: A Highly Concordant Synthesis of European and USA Datasets. In: Preedy. V., Patel V., eds. Cannabis, Cannabinoids and Endocannabinoids. London, U.K.,: Elsevier 2022:In Press.
8. Reece A.S., Hulse G.K. Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis. International Journal of Environmental Research and Public Health 2022;19(24):16721 - 76.
9. Reece A.S., Hulse G.K. Perturbation of 3D Nuclear Architecture, Epigenomic Aging and Dysregulation and Cannabinoid Synaptopathy Reconfigures Conceptualization of Cannabinoid Pathophysiology. Manuscript Submitted 2023
10. Nahas GG, Morishima A, Desoize B. Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Federation proceedings 1977;36(5):1748-52. [published Online First: 1977/04/01]
Competing interests:
No competing interests
05 March 2023
Albert Reece
Professor
University of Western Australia; Edith Cowan University
35 Stirling Hwy, Crawley, Perth, Western Austrtalia, Australia, 6009.
Rapid Response:
Cannabis neurotoxicity and genotoxicity
Dear Editor,
Dr. Smith is very much to be congratulated for boldly speaking the truth about neuropsychiatric complications of cannabis. However the concerns about cannabis neurotoxicity extend beyond mental illness seen in youth and adults as cannabis has been shown to be linked with autism spectrum disorder developing in children [1 2]. Furthermore based on US data the leading addiction researcher in the world has also linked cannabis with suicide [3].
Cannabis has also been linked with many birth defects in USA and Europe [4 5].
Cannabis has also been linked with many cancers in USA and Europe [6 7].
Cannabis has also been linked with aging based on the acceleration of 20 metrics of aging [8 9].
Cannabis and cannabinoids are widely agreed to be genotoxic. This includes warnings from the industry and warnings from regulators. As the genotoxic moiety has been shown to reside in the olivetol nucleus on the C-ring 10 this genotoxic effect can be assumed to be a general class effect applying to all the cannabinoids. This view is supported by the above cited epidemiological studies.
Many studies show that the toxic effects of cannabinoids on the epigenome and metabolome are both exponential – implying that as the prevalence of use, the intensity of daily use and the potency of cannabis products rises a “switch-like” effect of high dose cannabinoid exposure will kick in and once rare effects will become commonplace – as is indeed presently occurring.
Together this now impressive body of evidence indicates that cannabinoid genotoxicity is much more common and far more impactful than is generally realized. As the use of cannabis continues to grow the incidence of these deleterious genotoxic effects will continue to rise. Since genotoxicity and epigenotoxicity is inheritable for many generations drug policies of today will impact several generations to come.
Like an iceberg much of this is presently lying below the waterline of common public health consideration. If we are to charge unknowingly and unadvisedly into a sea of icebergs as did the captain of the Titanic our communities will likely share their fate.
References
1. Reece A.S., Hulse G.K. Impact of Converging Sociocultural and Substance-Related Trends on US Autism Rates: Combined Geospatiotemporal and Causal Inferential Analysis. European archives of psychiatry and clinical neuroscience 2022;19(13):7726-52. doi: 10.1007/s00406-022-01446-0
2. Schrott R, Acharya K, Itchon-Ramos N, et al. Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm. Epigenetics 2020;15(1-2):161-73. doi: 10.1080/15592294.2019.1656158 [published Online First: 2019/08/28]
3. Han B, Compton WM, Einstein EB, et al. Associations of Suicidality Trends With Cannabis Use as a Function of Sex and Depression Status. JAMA Netw Open 2021;4(6):e2113025. doi: 10.1001/jamanetworkopen.2021.13025 [published Online First: 20210601]
4. Reece AS, Hulse GK. Geotemporospatial and causal inference epidemiological analysis of US survey and overview of cannabis, cannabidiol and cannabinoid genotoxicity in relation to congenital anomalies 2001–2015. BMC Pediatrics 2022;22(1):47-124. doi: 10.1186/s12887-021-02996-3
5. Reece A.S., Hulse G.K. Cannabinoid- and Substance- Relationships of European Congenital Anomaly Patterns: A Space-Time Panel Regression and Causal Inferential Study. Environmental Epigenetics 2022;8(1):1-40.
6. Reece A.S., Hulse G.K. Geotemporospatial and Causal Inferential Epidemiological Overview and Survey of USA Cannabis, Cannabidiol and Cannabinoid Genotoxicity Expressed in Cancer Incidence 2003–2017: Part 1 – Continuous Bivariate Analysis. Archives of Public Health 2022;80:99-133. doi: doi.org/10.1186/s13690-022-00811-8
7. Reece A.S., Hulse G.K. Cannabis Genotoxicity and Cancer Incidence: A Highly Concordant Synthesis of European and USA Datasets. In: Preedy. V., Patel V., eds. Cannabis, Cannabinoids and Endocannabinoids. London, U.K.,: Elsevier 2022:In Press.
8. Reece A.S., Hulse G.K. Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis. International Journal of Environmental Research and Public Health 2022;19(24):16721 - 76.
9. Reece A.S., Hulse G.K. Perturbation of 3D Nuclear Architecture, Epigenomic Aging and Dysregulation and Cannabinoid Synaptopathy Reconfigures Conceptualization of Cannabinoid Pathophysiology. Manuscript Submitted 2023
10. Nahas GG, Morishima A, Desoize B. Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Federation proceedings 1977;36(5):1748-52. [published Online First: 1977/04/01]
Competing interests: No competing interests