By Mark Gold, MD
Limited information exists on marijuana use and male reproductive health. A recent study from Duke University evaluated differences in sperm quality resulting from tetrahydrocannabinol (THC) exposure in both rats and humans. Findings suggest that paternal marijuana use, prior to conception, may present epigenetic risks to potential offspring.
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Public perceptions pertaining to marijuana have evolved radically over the past 2 decades. While marijuana remains criminalized at the federal level, 33 states and the District of Columbia have legalized marijuana, in some capacity, for either medical or recreational use.1 According to the most recent National Survey on Drug Use and Health, nearly 26 million Americans, over the age of 12, currently use marijuana. While the gender gap is narrowing, men remain significantly more likely to use marijuana than women (11.7% vs. 7.3%, respectively).2
In 2017, approximately 1.9 million men, between the ages of 26 and 29, reported using marijuana in the past month. Given that the average age of first-time fathers in the U.S. is around 30, these findings suggest that a substantial number of “fathers-to-be” are using marijuana at the time of conception. Little is known, however, about the impact of paternal marijuana use on reproductive outcomes.
Epigenetics, which literally translates to “above” or “on top of” genetics, refers to the biological mechanism through which genes are activated and expressed. This process acts like a light switch, turning on or off how cells read certain heritable traits written within an individual’s unique genetic code. Sperm matures continually throughout adulthood, making it particularly vulnerable to potential epigenetic modifications, such as DNA methylation, that may result from marijuana use. This study explores differences in sperm profiles, based on cannabis exposure in both humans and rats, to better understand potential heritable effects.
Key Findings
Individuals who used marijuana can have higher and also can have significantly lower sperm concentrations, compared to those who did not, posing potential complications for fertility.
THC-exposed sperm was associated with significantly altered DNA, in both rat and human samples.
*Associations were even stronger among individuals with higher levels of THC in their urine, implying a “dose-response relationship” such that chronic marijuana users may be impacted more severely.
Authors identified three unique potential genetic pathways modified by THC exposure.
Looking to the Future
Past research suggests that offspring born to rats exposed to THC during adolescence demonstrate significant DNA alterations in their brains, display heightened drug-seeking behavior, and are at increased risk of developing opioid dependency over time, compared to controls.3 The present study is the first to extend this line of research to men of childbearing age, lending additional evidence for potential intergenerational, heritable consequences, resulting from paternal marijuana use. Just as other environmental triggers, such as air pollution, cigarette smoking, certain pesticides (i.e. DDT), and exposure to radiation are known to affect sperm health, THC may also increase the potential for genetic mutations.
For Clinicians
Primary care physicians and healthcare professionals, both inside and outside of substance use disorder treatment landscapes, should take time to educate patients about the impact of THC on sperm so individuals may consider potential implications for fertility and children conceived during periods of active use.
For Researchers
This article adds to a growing literature on the potential epigenetic impact of paternal marijuana use prior to conception. Findings must first be replicated in larger samples. Additionally, future longitudinal studies are necessary to explore the extent to which THC induced DNA alterations in sperm are passed down to offspring, as well as their long-term consequences.
For Policymakers
Marijuana potency continues to increase rapidly, with THC level increasing 300% over the past 20 years.4 Within the current political landscape and shift towards increased access to medical and recreational marijuana, policymakers should work closely with scientists to stay informed on the extent to which increased THC levels and evolving public attitudes impact men’s reproductive health.
For General Public
The full impact of passing THC-related DNA modifications onto offspring, and whether or not these changes are reversible is still unknown. Evidence of DNA alterations to existing Hippo signaling and Cancer genetic pathways may disrupt growth, enhance the potential for miscarriage, or impede healthy embryo development.
Methods
The authors employed a quantitative genome-scale approach, referred to as reduced representation bisulfite sequencing, to compare DNA methylation alterations in sperm across human and rat samples. A number of factors including, time since last ejaculation, semen volume, pH, morphology, and motility were controlled for across participants. Pyrosequencing, a DNA synthesizing method that relies on light detection, was implemented to identify genes with significant methylation differences. Data were then analyzed to uncover specific genetic pathways potentially impacted by paternal, preconception cannabis use.
Study Limitations
A relatively small sample size of human subjects, limiting the generalizability of study findings.
*24 males, age 18-40 years: (12 marijuana users & 12 non-users)
The methodological approach may fail to identify epigenetic modifications that affect multiple genes simultaneously.
Citation: Murphy SK, Itchon-Ramos N, Visco Z, et al. Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics. 2018;13(12):1208-1221.
References
State Marijuana Laws in 2018 Map. Retrieved from http://www.governing.com/gov-data/safety-justice/state-marijuana-laws-map-medical-recreational.html
Center for Behavioral Health Statistics and Quality. 2016 National Survey on Drug Use and Health: Detailed Tables. Retrieved from https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2016/NSDUH-DetTabs-2016.pdf
Tang WWC, Dietmann S, Irie N, et al. A unique gene regulatory network resets the human germline epigenome for development. Cell.
ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in cannabis potency over the last 2 decades (1995–2014): analysis of current data in the United States.
Feiby L Nassan, Mariel Arvizu, Lidia Mínguez-Alarcón, Paige L Williams, Jill Attaman, John Petrozza, Russ Hauser, Jorge Chavarro, EARTH Study Team; Marijuana smoking and markers of testicular function among men from a fertility centre, Human Reproduction, dez002. Retrieved from https://doi.org/10.1093/humrep/dez002
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.