Genetic Damage

UNC study: Even one-time marijuana use can cause birth defects – especially if used with alcohol

CHAPEL HILL – A new study published in Scientific Reports, a Nature Research journal, shows how a one-time exposure during early pregnancy to marijuana incredients known as cannabinoids (CBs) – both synthetic and natural – can cause growth issues in a developing embryo. This is the first research to show such a connection in mammals.

The study was performed in mice, which are very accurate models for the development that occurs during early pregnancy, according to the study’s senior author, Scott Parnell, PhD, assistant professor of cell biology and physiology in the UNC School of Medicine.

“The development of the embryo in this time period is very similar across all vertebrates,” said Parnell, a member of the UNC Bowles Center for Alcohol Studies. “In this study we also test a synthetic cannabinoid in zebrafish that yielded similar growth deformations as the natural CBs. Having the same results across animal models reinforces our findings.”

In this study, the brain and facial developmental effects caused by one-time exposure to CBs – CBD and THC (the primary ingredients of marijuana) – are very similar to what is seen in fetal alcohol syndrome (FAS). Parnell and colleagues also found that when CBs and alcohol were used together, the likelihood of these birth defects more than doubled. They went on to show that these drugs may be causing defects by interacting on a basic cellular level and disrupting signaling between molecules and cells that control growth and development.


Lifetime marijuana use and epigenetic age acceleration: A 17-year prospective examination

Conclusions: Marijuana use predicted epigenetic changes linked to accelerated aging, with evidence suggesting that effects may be primarily due to hydrocarbon inhalation among marijuana smokers. Further research is warranted to explore mechanisms underlying this linkage.


Geotemporospatial and causal inference
epidemiological analysis of US survey
and overview of cannabis, cannabidiol
and cannabinoid genotoxicity in relation
to congenital anomalies 2001–2015

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767720/pdf/12887_2021_Article_2996.pdf


Genetic effects of marijuana

Abstract

Marijuana and its constitutive cannabinoids–tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD)–markedly affect mammalian cells. Cytogenetic studies have revealed that cannabinoids induce chromosome aberrations in both in vivo and in vitro studies. These aberrations include chromosomal breaks, deletions, translocations, errors in chromosomal segregation, and hypoploidy, and are due to the clastogenic action of cannabinoids or to cannabinoid-induced disruption of mitotic events or both. Conflicting reports of the cytogenetic effects of cannabinoids are partially explained by the different experimental protocols, cell types, and animals used by investigators. Cannabinoids also suppress macromolecular synthesis (DNA, RNA, and protein) as well as reduce the level of histone gene expression. In general these studies show that cannabinoids are detrimental to the health of an individual.

https://pubmed.ncbi.nlm.nih.gov/2174024/


DNA Damaging Effects, Oxidative Stress Responses and Cholinesterase Activity in Blood and Brain of Wistar Rats Exposed to Δ9-Tetrahydrocannabinol

Abstract

Currently we are faced with an ever-growing use of Δ9-tetrahydrocannabinol (THC) preparations, often used as supportive therapies for various malignancies and neurological disorders. As some of illegally distributed forms of such preparations, like cannabis oils and butane hash oil, might contain over 80% of THC, their consumers can become intoxicated or experience various detrimental effects. This fact motivated us for the assessments of THC toxicity in vivo on a Wistar rat model, at a daily oral dose of 7 mg/kg which is comparable to those found in illicit preparations. The main objective of the present study was to establish the magnitude and dynamics of DNA breakage associated with THC exposure in white blood and brain cells of treated rats using the alkaline comet assay. The extent of oxidative stress after acute 24 h exposure to THC was also determined as well as changes in activities of plasma and brain cholinesterases (ChE) in THC-treated and control rats. The DNA of brain cells was more prone to breakage after THC treatment compared to DNA in white blood cells. Even though DNA damage quantified by the alkaline comet assay is subject to repair, its elevated level detected in the brain cells of THC-treated rats was reason for concern. Since neurons do not proliferate, increased levels of DNA damage present threats to these cells in terms of both viability and genome stability, while inefficient DNA repair might lead to their progressive loss. The present study contributes to existing knowledge with evidence that acute exposure to a high THC dose led to low-level DNA damage in white blood cells and brain cells of rats and induced oxidative stress in brain, but did not disturb ChE activities.


Lifetime marijuana use and epigenetic age acceleration: A 17-year prospective examination

Conclusions

Marijuana use predicted epigenetic changes linked to accelerated aging, with evidence suggesting that effects may be primarily due to hydrocarbon inhalation among marijuana smokers. Further research is warranted to explore mechanisms underlying this linkage.