Closing the Loophole on Hemp-Derived Cannabis Products: A Public Health Priority (Journal of American Medical Association)
…due to limited regulation, psychotropic, hemp-derived cannabis products have marketing features that may appeal to youth. For example, such products are available as chocolates, gummies, cookies, and brownies and the packaging and advertisements often use bright and colorful designs. In addition, hemp-derived cannabis vape cartridges come in a wide range of sweet and fruity flavors, which increase appeal among youth and young adults. Because of their similarity to candy and food products, accidental exposure by children, adults, and animals is a concern. Between January 1, 2021, and February 28, 2022, national poison control centers received reports of 2362 cases of Δ8-THC exposures, of which 40% involved accidental exposure to Δ8-THC (82% among youth), 70% required evaluation at a health care facility, 8% were admitted to a critical care unit, and 1 pediatric death was reported.2 Animal poison control centers have also seen an increase in reports of accidental pet exposure to Δ8-THC.2
The increasing marketing of psychotropic, hemp-derived cannabis products makes clear that a regulated hemp market that manufactures and sells products with more oversight and stricter safety standards is urgently needed. Many of the potential harms of hemp-derived cannabis products stem from a lack of regulation, including the potential for harmful contaminants, accidental exposure, cross-product sale with tobacco and alcohol, and youth appeal.
State and federal regulators should prioritize new hemp policies that ensure prohibition of sale to minors; set requirements for testing, packaging, and labeling; and place limits on potency and concentration of psychotropic products. The public health implications of psychotropic, hemp-derived cannabis products remain understudied. However, the lack of regulation over the marketing and synthesis of these products, combined with the widespread availability, warrants national surveillance and new hemp policies that close loopholes and prioritize public health.
Cannabinoid Epigenotoxicity and Genotoxicity (A Response to Harlow)
Whilst the observations of Harlow and colleagues are welcomed, by failing to mention cannabinoid epi/genotoxicity they radically understate the case against multiple cannabinoid isomers.
It was shown long ago in vitro that many cannabinoids are genotoxic 1 a finding which has since been confirmed in multiple human epidemiological studies 2,3. Moreover cannabinoid genotoxicity is widely agreed upon by producers, marketers and regulators and is referred to in FDA warnings for cannabinoid medicines. Indeed it can be argued that it is the established fact of cannabinoid genotoxicity which makes an alternative parallel universe for cannabinoid regulation necessary given obviously serious concerns from FDA and comparable drug regulators internationally.
Cannabinoid genotoxicity has been classically expected to be expressed in terms of cancer, congenital anomaly and aging (CaCAAg) data 2,3. A growing body of evidence across all three domains provides strong support for the clinical implications of all three areas of potential public health relevance.
Most concerning of all is an increasing stream of evidence from human, rodent and human embryonic stem cell data for epigenomic changes which implies multigenerational impacts to brain, heart and body wall development, cancer incidence and aging 4,5.
Whist we are used to seeing studies across the CaCAAg spectrum performed in each of the three domains the most recent studies from leading groups indicate that genotoxic outcomes across the three CaCAAg domains can co-occur simultaneously. Thus in a recent paper examining prenatally cannabis exposed (PCE) mouse heart development hearts were shown to be smaller at birth but then underwent a rapid growth spurt to become larger and more fibrotic and stiffer in the pre-adolescent period phenocopying aspects of cardiac aging, a syndrome which is known to predispose to later increased heart disease, the highest ranking killer disease internationally 5. This finding potentially links teratogenesis, aging, adult disease and death.
Similarly in epigenomic studies both of human (and rodent) sperm and differentiated spermatogonial stem cells both autism and cancer-related genes (Prenatally Expressed Genes 3 and 10) were implicated following (modelled) PCE 4. This finding links teratogenesis, neurotoxicity and cancerogenesis.
Other studies show that the pro-aging effects of cannabis on cellular age increase with age and age-squared across the lifespan.
These indications of the simultaneous effects of cannabis across the three CaCAAg domains suggest that cannabis epi/genotoxicity is a major public health player and implies that cannabinoids generally should urgently be regulated in line with all other known major epi/genotoxins.
Albert Stuart Reece, MD, PhD | Department of Psychiatry, University of Western Australia, Edith Cowan University
1. Nahas GG et al. Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Federation proceedings. Apr 1977;36(5):1748.
2. Reece A.S., Hulse G.K. Cannabis, Cannabidiol, Cannabinoids and Multigenerational Policy Engineering. 2022; In Press.
3. Reece A.S., Hulse G.K. Epidemiological Overview of Multidimensional Chromosomal and Genome Toxicity of Cannabis Exposure in Congenital Anomalies and Cancer Development Scientific Reports. 2021;11(1):13892.
4. Lee, K., Laviolette, S.R. & Hardy, D.B. Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life. Pediatr Res 90, 532–539 (2021). https://doi.org/10.1038/s41390-021-01511-9;
5. Robinson GI... Maternal Delta-9-Tetrahydrocannabinol Exposure Induces Abnormalities of the Developing Heart in Mice. Cannabis Cannabinoid Res. Oct 17 2022.