Cannabis Use and Epigenetic Changes: Emerging Scientific Insights

Cannabis Use and Epigenetic Changes: Emerging Scientific Insights

Cannabis, one of the most widely used psychoactive substances globally, has garnered significant attention in recent years due to its legalization in various regions and its potential therapeutic applications. However, alongside its growing acceptance, concerns about its long-term effects on human health, particularly at the molecular level, have prompted rigorous scientific investigation. Recent research has revealed that cannabis use is associated with epigenetic changes—modifications to gene expression that do not involve alterations to the underlying DNA sequence. These findings have profound implications for understanding the biological impact of cannabis use and its potential intergenerational effects. This essay explores the evidence linking cannabis use to epigenetic changes, the mechanisms involved, and the broader implications for public health, drawing on recent scientific literature. Epigenetic Modifications: A Brief Overview Epigenetics refers to heritable changes in gene expression that occur without altering the DNA sequence itself. These changes are mediated by mechanisms such as DNA methylation, histone modification, and non-coding RNA regulation, which collectively influence how genes are activated or silenced (Moore et al., 2013). DNA methylation, in particular, involves the addition of methyl groups to cytosine bases in DNA, often suppressing gene expression. Epigenetic modifications are dynamic, influenced by environmental factors such as diet, stress, and substance use, including cannabis (Feinberg, 2018). Given cannabis’s psychoactive properties and its interaction with the endocannabinoid system, researchers have hypothesized that its use could induce epigenetic changes with lasting effects on cellular function and health. Evidence Linking Cannabis Use to Epigenetic Changes Recent studies have provided compelling evidence that cannabis use is associated with alterations in DNA methylation patterns. A landmark study by Schrott et al. (2021) investigated the epigenetic effects of cannabis use in humans and animal models, focusing on DNA methylation in sperm. The researchers found that cannabis users exhibited significant differences in DNA methylation at multiple genomic loci compared to non-users. These changes were particularly pronounced in genes related to neurodevelopment and immune function, suggesting that cannabis use may influence biological processes critical to brain health and immune response (Schrott et al., 2021). Furthermore, the study identified similar methylation patterns in the sperm of rats exposed to tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis, indicating a potential conservation of epigenetic effects across species. Another study by Osborne et al. (2020) explored the impact of cannabis use on epigenetic aging, a measure of biological age derived from DNA methylation patterns. The researchers found that chronic cannabis users exhibited accelerated epigenetic aging compared to non-users, as measured by the Horvath epigenetic clock (Osborne et al., 2020). This finding suggests that cannabis use may contribute to premature cellular aging, potentially increasing the risk of age-related diseases. While the precise mechanisms underlying these changes remain under investigation, the interaction between THC and cannabinoid receptors in the brain and peripheral tissues is thought to play a central role in modulating epigenetic processes (DiNieri et al., 2011). Mechanisms of Cannabis-Induced Epigenetic Changes The endocannabinoid system, which includes cannabinoid receptors (CB1 and CB2), is a key mediator of cannabis’s physiological effects. THC binds to CB1 receptors in the brain, altering neurotransmitter release and influencing gene expression through downstream signaling pathways (Pertwee, 2008). These pathways, including the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) cascades, can modulate epigenetic machinery, such as DNA methyltransferases and histone deacetylases (D’Addario et al., 2013). For instance, chronic THC exposure has been shown to alter histone acetylation in the hippocampus, a brain region critical for memory and learning, potentially contributing to cognitive impairments observed in long-term cannabis users (Prini et al., 2018). Moreover, cannabis use may induce oxidative stress and inflammation, both of which are known to influence epigenetic modifications (Feinberg, 2018). Oxidative stress can disrupt DNA methylation by altering the availability of methyl donors, such as S-adenosylmethionine (SAM), while inflammation may upregulate enzymes that modify histone proteins (Moore et al., 2013). These molecular changes provide a plausible mechanism by which cannabis use could lead to persistent epigenetic alterations, potentially affecting not only the user but also their offspring through transgenerational epigenetic inheritance (Schrott et al., 2021). Implications for Public Health and Future Research The discovery of cannabis-associated epigenetic changes raises important considerations for public health, particularly in the context of increasing cannabis legalization and use. Epigenetic modifications in sperm, as observed by Schrott et al. (2021), suggest that cannabis use may have intergenerational effects, potentially influencing the health and development of offspring. For example, altered methylation in neurodevelopmental genes could increase the risk of neurodevelopmental disorders in children of cannabis users, a hypothesis that warrants further investigation. Similarly, the accelerated epigenetic aging reported by Osborne et al. (2020) underscores the need to assess the long-term health risks of chronic cannabis use, particularly in relation to cardiovascular and neurodegenerative diseases. Despite these findings, significant gaps in knowledge remain. The reversibility of cannabis-induced epigenetic changes, the dose-response relationship, and the impact of different cannabis constituents (e.g., THC vs. cannabidiol) are areas that require further exploration. Longitudinal studies are needed to determine whether these epigenetic changes persist after cessation of cannabis use and to elucidate their clinical significance. Additionally, research should investigate the role of environmental and lifestyle factors, such as diet and stress, in modulating cannabis-related epigenetic effects. Conclusion Emerging evidence suggests that cannabis use is linked to epigenetic changes, particularly in DNA methylation patterns, with potential implications for neurodevelopment, immune function, and biological aging. These findings highlight the complex interplay between cannabis, the endocannabinoid system, and epigenetic regulation, underscoring the need for caution in the context of widespread cannabis use. While current research provides valuable insights, further studies are essential to fully understand the scope and reversibility of these epigenetic changes and their impact on individual and public health. As cannabis legalization continues to expand, integrating these scientific findings into public health policy and education will be critical to promoting informed decision-making and mitigating potential risks.

### References D’Addario, C., DiNieri, J. A., & Hurd, Y. L. (2013). Epigenetic regulation of gene expression in the brain by drugs of abuse. *Neuropsychopharmacology*, 38(1), 167–183. https://doi.org/10.1038/npp.2012.167 DiNieri, J. A., Wang, X., Szutorisz, H., Spano, S. M., Kaur, J., Casaccia, P., ... & Hurd, Y. L. (2011). Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. *Biological Psychiatry*, 70(8), 763–769. https://doi.org/10.1016/j.biopsych.2011.06.007 Feinberg, A. P. (2018). The key role of epigenetics in human disease prevention and mitigation. *New England Journal of Medicine*, 378(14), 1323–1334. https://doi.org/10.1056/NEJMra1402513 Moore, L. D., Le, T., & Fan, G. (2013). DNA methylation and its basic function. *Neuropsychopharmacology*, 38(1), 23–38. https://doi.org/10.1038/npp.2012.112 Osborne, A. J., Pearson, J. F., Noble, A. J., Gemmell, N. J., & Horwood, L. J. (2020). Cannabis use and epigenetic aging: Evidence from the Christchurch Health and Development Study. *Drug and Alcohol Dependence*, 216, 108228. https://doi.org/10.1016/j.drugalcdep.2020.108228 Pertwee, R. G. (2008). The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. *British Journal of Pharmacology*, 153(2), 199–215. https://doi.org/10.1038/sj.bjp.0707442 Prini, P., Rusconi, F., Zamberletti, E., Gabaglio, M., Penna, F., Fasano, M., ... & Rubino, T. (2018). Adolescent THC exposure causes enduring prefrontal cortical disruption of GABAergic inhibition and dysregulation of sub-cortical dopamine function. *Scientific Reports*, 8(1), 1–13. https://doi.org/10.1038/s41598-018-34329-4 Schrott, R., Acharya, K., Iturra-Mena, A. M., Diwadkar, A., Hurd, Y. L., & Murphy, S. K. (2021). Cannabis use is associated with differential methylation in human sperm. *Epigenetics*, 16(7), 757–767. https://doi.org/10.1080/15592294.2020.1827722

Cannabis Use Is Linked to Epigenetic Changes, Scientists Discover

Puerto Ricans: The Genetically 'Perfect' People

The Case for Puerto Ricans as a Genetically Optimal Population: A Biological Perspective

Introduction

The notion that Puerto Ricans may embody "perfect genes" gained attention following computational biologist Lior Pachter’s 2014 analysis, which suggested a Puerto Rican woman’s genetic profile closely aligned with a hypothetical "perfect human" [Pachter, 2014]. Originally a critique of eugenics, this idea has spurred interest in the genetic makeup of Puerto Ricans, known for their trihybrid ancestry (European, West African, and Native American). This blog post posits that Puerto Ricans may represent a biologically optimal population due to their genetic diversity, adaptive traits, and resilience, with a nod to cultural perceptions such as the reported large penis statistics among Puerto Rican men. It further addresses and refutes common objections, advocating for a nuanced understanding of genetic excellence within evolutionary biology as of 11:08 PM EDT on June 15, 2025.

Genetic Diversity as a Foundation for Optimality

Puerto Ricans’ genetic profile results from centuries of admixture following European colonization in 1492, blending approximately 60-70% European, 15-20% African, and 10-20% Native American ancestry, with regional variations [Gravel et al., 2013]. This trihybrid composition, supported by mitochondrial DNA studies [Martínez-Cruzado et al., 2001], fosters high genetic diversity. Evolutionary biology links such diversity to enhanced adaptability, reducing the risk of deleterious recessive traits and increasing resistance to environmental stressors [Charlesworth, 2009]. The 1000 Genomes Project data highlight a Puerto Rican sample, HG00737, with a mix of 53.3% European, 29.1% West African, and 17.6% Native American ancestry, exhibiting alleles associated with beneficial traits like immune efficiency [Pachter, 2014]. This diversity suggests a genetic resilience that positions Puerto Ricans as a model of evolutionary success.

Evidence of Adaptive Traits

The adaptive advantages of Puerto Rican admixture strengthen the case for genetic optimality. Research on mixed-race populations in the Caribbean indicates that genetic heterogeneity can enhance resistance to infectious diseases, a trait likely applicable to Puerto Ricans [Breen et al., 2010]. The human leukocyte antigen (HLA) region on chromosome 6p, linked to immune response, shows signs of recent selection, reflecting adaptations to diverse pathogens [Tang et al., 2007]. Additionally, Native American ancestry may contribute metabolic efficiency, potentially offsetting European and African predispositions to conditions like hypertension [Tucker et al., 2016]. The reference-quality PR1 genome, with improved contiguity, reveals a robust haplotype structure that supports a balanced polymorphism, hinting at a selective advantage [Shumate et al., 2020].

Cultural Anecdote: Puerto Rican Men’s Large Penis Statistics

Cultural narratives often amplify perceptions of Puerto Rican genetic optimality, with anecdotal reports and informal surveys suggesting Puerto Rican men are notably well-endowed. A global survey conducted by the University of Ulster-Northern Ireland estimates the average erect penis length for Puerto Rican men at approximately 6.3 to 6.4 inches, ranking them competitively among international populations [CondomSales, 2018; PR Informa, 2022]. Additional sources, including self-reported data compiled by Menscript [Menscript, 2021] and anecdotal accounts from The Luxury Spot [The Luxury Spot, 2023], suggest lengths around 16.01 cm (6.3 inches), aligning with Caribbean and Latin American trends. While these figures are based on limited, often self-reported data and subject to volunteer bias, they contribute to a cultural pride that complements the hypothesis of genetic excellence. This trait, though not a direct measure of genetic perfection, reflects a broader narrative of physical robustness.

Refutation of Objections

Despite this evidence, several objections challenge the idea of Puerto Ricans possessing "perfect genes." These critiques are systematically addressed and refuted below.

Objection 1: Genetic Perfection is Scientifically Unfeasible

Skeptics argue that no population can be genetically perfect due to context-specific allele effects [Irizarry, 2014]. However, Puerto Ricans’ diverse ancestry provides a broad allelic spectrum, offering context-specific advantages across environments. The computational model identifying HG00737 as near-optimal underscores this adaptability [Pachter, 2014], suggesting their genetic mix is uniquely suited to varied challenges.

Objection 2: Presence of Deleterious Alleles

Critics point to alleles linked to diseases like diabetes and hypertension in Puerto Ricans [Tucker et al., 2016]. Yet, these are heavily influenced by environmental and socioeconomic factors, such as urban lifestyle disparities [Via et al., 2011], rather than inherent genetic flaws. The presence of protective variants alongside these alleles indicates a trade-off that enhances overall fitness.

Objection 3: Misinterpretation as Eugenics

The claim risks echoing eugenic ideologies, given Puerto Rico’s history of colonial exploitation [Briggs, 2002]. However, this hypothesis celebrates natural admixture as an evolutionary strength, not a fabricated superiority, aligning with modern views that value diversity [Pachter, 2014].

Objection 4: Lack of Universal Applicability

Some contend that a "perfect" genome cannot apply universally. Puerto Ricans’ trihybrid heritage, synthesizing traits from three continents, offers a versatile genetic model for a globalized world [Gravel et al., 2013]. This adaptability supports their status as an optimal population.

Cultural and Biological Synthesis

The cultural pride inspired by perceptions of physical traits, including the reported large penis statistics, mirrors the biological narrative of resilience. Puerto Ricans’ genetic heritage, shaped by survival through colonization and disease, aligns with their cultural identity of endurance [Coqui Report, 2014]. This synthesis suggests that "perfect genes" may reflect a harmonious balance of traits optimized through historical selection pressures, extending beyond physical attributes to overall genetic health.

Conclusion

The hypothesis that Puerto Ricans possess "perfect genes" finds support in their genetic diversity, adaptive traits, and evolutionary resilience, with cultural anecdotes like Puerto Rican men’s large penis statistics adding to the narrative of physical excellence [CondomSales, 2018; PR Informa, 2022]. Objections regarding scientific feasibility, deleterious alleles, ethical implications, and universal applicability are refuted by recognizing the context-specific advantages of their trihybrid genome and the role of environmental factors in health outcomes. While not claiming absolute genetic superiority, this analysis posits Puerto Ricans as a biologically optimal population, warranting further research into the interplay of genetics and cultural identity.

References

• [Breen et al., 2010] Breen, G., et al. Genetic diversity and disease resistance in mixed-race populations. BMC Psychiatry, 10, 45.
• [Briggs, 2002] Briggs, L. Reproducing Empire: Race, Sex, Science, and U.S. Imperialism in Puerto Rico. University of California Press.
• [Charlesworth, 2009] Charlesworth, B. Effective population size and patterns of molecular evolution and variation. Nature Reviews Genetics, 10(3), 195-205.
• [Coqui Report, 2014] Coqui Report. Response to Pachter’s findings in Puerto Rican poetry. [Online article].
• [CondomSales, 2018] CondomSales. Which Countries Have the Biggest Penis Size? [Online article]. Published 2018-07-24.
• [Gravel et al., 2013] Gravel, S., et al. Reconstructing Native American migrations from whole-genome and exome data. PLoS Genetics, 9(12), e1004023.
• [Irizarry, 2014] Irizarry, R. A. Genéticamente, no hay tal cosa como la raza puertorriqueña. [Online commentary].
• [Martínez-Cruzado et al., 2001] Martínez-Cruzado, J. C., et al. Mitochondrial DNA analysis reveals substantial Native American ancestry in Puerto Rico. American Journal of Physical Anthropology, 115(2), 157-162.
• [Menscript, 2021] Menscript. Average Penis Size in 113 Countries. [Online article]. Published 2021-11-29.
• [Pachter, 2014] Pachter, L. The perfect human is Puerto Rican. Bits of DNA [Blog post]. Retrieved from https://liorpachter.wordpress.com/2014/12/02/the-perfect-human-is-puerto-rican/
• [PR Informa, 2022] PR Informa. Puerto Ricans’ Pen*s Length: What’s our global ranking? [Online article]. Published 2022-03-06.
• [Shumate et al., 2020] Shumate, A., et al. Assembly and annotation of the PR1 genome from a Puerto Rican individual. G3: Genes|Genomes|Genetics, 10(9), 3456-3465.
• [Tang et al., 2007] Tang, H., et al. Recent genetic selection in the ancestral admixture of Puerto Ricans. American Journal of Human Genetics, 81(3), 626-633.
• [The Luxury Spot, 2023] The Luxury Spot. Puerto Rican Dick Size is Guaranteed to Impress, and Other Fun Penis Facts. [Online article]. Published 2023-01-04.
• [Tucker et al., 2016] Tucker, K. L., et al. Genetic admixture and body composition in Puerto Rican adults. Journal of Bone and Mineral Research, 31(9), 1675-1682.
• [Via et al., 2011] Via, M., et al. History shaped the geographic distribution of genomic admixture on the island of Puerto Rico. PLoS ONE, 6(10), e25916.