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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Curr Opin Endocrinol Diabetes Obes. 2021 Dec 1;28(6):558–565. doi: 10.1097/MED.0000000000000686

Effects of marijuana on reproductive health: preconception and gestational effects

Kimberly S Ryan a,*, Jasper C Bash b,*, Carol B Hanna c, Jason C Hedges b, Jamie O Lo a,c
PMCID: PMC8580253  NIHMSID: NIHMS1752626  PMID: 34709212

Abstract

Purpose of review

Recent widespread legalization changes have promoted the availability of marijuana and its increased potency and perceived safety. The limited evidence on reproductive and perinatal outcomes from marijuana exposure is enough to warrant concern and action. The objective of this review is to provide a current and relevant summary of the recent literature surrounding this topic.

Recent findings

The available published studies on the effect of marijuana exposure on reproductive health and pregnancy outcomes are conflicting. Human studies are often observational or retrospective and confounded by self-report and polysubstance use. However, the current, limited evidence suggests that marijuana use adversely affects male and female reproductive health. Additionally, prenatal marijuana exposure has been reported to be associated with an increased risk of preterm birth and small for gestational age infants.

Summary

With the increasing prevalence of marijuana use, there is an urgent need for evidence-driven recommendations and guidelines for couples interested in conception, affected by infertility or who are expecting. At this time, no amount of marijuana use during conception or pregnancy is known to be well tolerated and the limited available evidence suggests that the safest choice is to abstain.

Keywords: cannabis, fertility, marijuana, maternal substance use, pregnancy, reproductive function, reproductive health

INTRODUCTION

Marijuana is the most commonly used drug worldwide [1], especially among men and women of reproductive age. This is concerning as marijuana use may affect both male and female reproductive health by interfering with the body’s innate endocannabinoid system. Cannabinoid receptors are present throughout the body, including the hypothalamus, pituitary, ovary, uterus, testes, and sperm [2].

Research to date suggests that marijuana use may affect the processes involved with reproduction including the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, menstrual cyclicity, ovulation, and sperm parameters [2]. Additionally, as its main active ingredient, delta-9-tetrahydrocannabinol (THC), can cross the placenta, there is concern for potential harmful effects to the developing fetus and offspring from maternal use during pregnancy and lactation.

Most of the marijuana research that exists surrounding its effects on reproductive health and pregnancy are limited and conflicting. The majority of the available human studies are observational or retrospective, confounded by polysubstance use, and rely on self-report thus contributing to the heterogeneity in reported results [3]. Prior animal studies primarily studied the effects following acute marijuana exposure, often intravenous, which is not representative of human use. Contemporary marijuana products and edibles also have higher quantities of THC than when much of the existing marijuana research was performed [4–6].

This review aims to summarize the literature and provide an update on our current understanding of marijuana use exposure for an understudied but timely aspect of reproductive health and pregnancy that will open an important area of inquiry into better understanding how marijuana exposure can impact a couples’ fertility and pregnancy outcomes.

EFFECTS OF DELTA-9-TETRAHYDROCANNABINOL ON FEMALE REPRODUCTIVE HEALTH PRECONCEPTION

The available human literature on the effects of marijuana use on female reproductive health is limited and largely derived from women undergoing assisted reproductive technology.

The effects of acute delta-9-tetrahydrocannabinol exposure in preclinical models

Early studies mostly used small animal models to study the effects of THC and the impact of acute exposure on the hormonal axis, including the hypothalamus and anterior pituitary. An older study in proestrus rats demonstrated that the administration of THC (2 mg per rat) suppressed plasma levels of LH, FSH, and prolactin and delayed ovulation by 24 h [7]. Chakravarty et al. [8] also revealed that intraperitoneal administration of high, acute doses of THC in rats significantly decreased serum LH and prolactin. Proestrus rats exposed to THC had a significant dose–response decrease in hypothalamic LH-releasing hormone content, suggesting a possible hypothalamic impact from THC use [8]. Additionally, serum prolactin levels were decreased while LH and FSH serum levels were similar to that of dioestrous rats [8]. Another former study noted that THC exposure in dioestrous female rats significantly decreased plasma concentrations of LH and FSH, whereas those post ovariectomy had varying responses [9].

The effects of chronic delta-9-tetrahydrocannabinol exposure in preclinical models

The nonhuman primate (NHP) is a strong translational model because of its similar plasma disposition of THC [10] and menstrual cycle lengths to that of humans [11–13]. Several reports have used this model to study the implications of chronic THC use. In a study by Asch et al. [14], daily THC was administered by intramuscular injection to regular cycling NHPs the first 18 days of the menstrual cycle and anovulation was subsequently observed in a majority of the female individuals, supporting the prior findings described in rats [7]. Another study injected regular cycling NHPS (n = 5) with THC (2.5mg/kg/day) three times a week on varying days over 230 days total or two consecutive ovulatory cycles [15]. Initially, the animals became anovulatory with abnormal serum hormones, however, with tolerance to THC, they eventually restored normal menstrual cyclicity, ovulation and hormone levels [15]. Similarly, in ovariectomized NHPs, regular intramuscular injections of THC resulted in a reversible reduction in LH levels [16]. A more recent study (n = 8) of chronic THC, edible consumption reported that increasing doses of THC (0.625, 1.25, 2.5, or 5mg/kg) resulted in a dose–response relationship of significantly increased menstrual cycle length and FSH levels suggestive of ovulatory dysfunction [17■■].

Overall, the research reports concerning the effects of THC on reproductive health have indicated that the major pharmacologic site of action is central in both NHPs [18–20] and other animal models [8,21,22], whereas other studies have indicated a direct THC effect at the gonadal level [7].

The effect of marijuana use on female reproductive health in humans

Many human studies have reviewed women’s perception of marijuana use in relation to fertility. Within a cross-sectional study, 270 infertility patients were surveyed regarding marijuana usage, perception of the effect on infertility and pregnancy, and cessation because of infertility [23■]. Of those surveyed, 13% reported marijuana use and those who used more recently were less likely to think that marijuana can negatively impact fertility. Additionally, the perception of harm from marijuana varied with form of use. Particularly, edibles have gained popularity and are perceived to be safe despite evidence of increased danger from over intoxication [24].

Effects of delta-9-tetrahydrocannabinol on fertility outcomes

A study from 1990 found that women who had smoked marijuana within 1 year of trying to conceive were twice as likely to have infertility because of ovulatory dysfunction than their counterparts who did not use marijuana [relative risk (RR) = 2.1; 95% confidence interval (CI) 1.1–4.0] [25]. However, a recent observational study (n = 4200) found little association between female marijuana use and spontaneous conception rates after controlling for confounders [26]. Similarly, retrospective review of cross-sectional survey data from female respondents noted no significant impact of marijuana use on time to conception [27]. Most recently, a secondary analysis of women with a history of prior first trimester pregnancy loss found preconception marijuana use to be associated with reduced fecundability despite an increased frequency of intercourse [28■■].

Effects of delta-9-tetrahydrocannabinol on assisted reproductive technology outcomes

Research studying the effects of THC on ART outcomes have noted that the amount of lifetime heavy marijuana use adversely affects in-vitro fertilization and gamete intra-fallopian transfer (IVF/GIFT) [29]. In a prospective study of 221 couples, women who smoked marijuana within lyear prior to IVF/GIFT had 25% fewer oocytes retrieved and these couples also had 28% fewer oocytes fertilized [29]. A more recent prospective study found that among women undergoing ART with a positive beta-human chorionic gonadotropin (bHCG), those who were marijuana smokers at enrollment had more than double the adjusted probability of pregnancy loss than past marijuana smokers or nonmarijuana smokers (54 vs. 26%; P = 0.0003) [30].

EFFECTS ON MALE REPRODUCTIVE HEALTH PRECONCEPTION

Marijuana is the most commonly used drug in the United States [1] and is most prevalent among men of reproductive age, thus understanding its impact on male fertility is critical [31]. It is plausible that marijuana can disrupt sperm function as cannabinoid one receptors (CB1) are present on sperm and the endocannabinoid system has a role in regulating male reproduction [32–35]. The available human literature is variable partly as studies are often from assisted reproductive centers or have polysubstance abuse histories, limiting the generalizability of the findings and precluding determination of a causal effect specific to marijuana [26,20,36–38].

The effects of delta-9-tetrahydrocannabinol on male reproductive hormones

The hypothalamic–pituitary–gonadal (HPG) axis plays a critical role in both spermatogenesis and testosterone production. This axis regulates the release of two vital gonadotropin hormones for reproduction, FSH and LH, which act on cells in the testes including Leydig cells, which produce testosterone.

Follicle-stimulating hormone and luteinizing hormone

The few studies that have investigated the effect of acute or chronic marijuana exposure on FSH levels in male individuals have found minimal effect [39], nor did it alter their FSH response to exogenous gonadotropin-releasing hormone (GnRH) [40]. In contrast, there is robust evidence to support the inhibitory effect of marijuana on LH. A prior study noted that plasma LH levels are significantly reduced 60 min after administration of low dose THC in male rats (0.5 mg THC/kg body weight) [41]. Vescovi et al. [40] studied daily marijuana users (n = 10) and never-user controls (n = 10) aged 19–20 years old, and reported significantly lower serum LH levels in users, as well as a weaker LH response to exogenous GnRH. Similar findings were noted by Cone et al. [39] that plasma LH was significantly depressed after smoking marijuana cigarettes versus placebo cigarettes. In a study comparing two groups of chronic THC users, no difference in LH was noted between those who smoked five to nine cigarettes weekly versus more than ten cigarettes weekly, suggesting an upper limit on the dose-dependent effect of THC on LH [42].

Testosterone

A recent systematic review of 91 articles noted that existing literature regarding chronic THC consumption and testosterone changes are mixed [43]. In-vivo acute (10 mg/kg) and chronic (2 mg/kg) THC exposure in rats caused decreased testosterone bio-synthesis [44], whereas mice showed a dose-dependent decrease in testicular LH receptor expression in the testes when similarly exposed [45]. Long-term THC exposure in mice resulted in a blocked testosterone response to HCG in the testes whereas a single oral THC dose caused decreased LH and serum testosterone levels [46]. The above preclinical findings support multifactorial causes for hypogonadism in THC-exposed male individuals, which is less well studied in the human literature. A large group of young Danish men ages 18–28 years old reported 7% higher testosterone levels in THC users compared with nonusers [47]. A subsequent study using the National Health and Nutrition Examination Survey (NHANES) database found no difference in testosterone levels between marijuana ever-users (n = 1055) and never users (n = 533) [48]. They did report an inverse relationship between duration of THC abstinence and testosterone levels, suggesting that the effect of THC on testosterone may be more acute and transient [48].

Testicular size

Preclinical research suggest a dose-dependent association between chronic marijuana use and reduction in the prostate and seminal vesicle weight [45,49–51] of mice and rats as well as testicular atrophy in dogs [52]. The mechanism for these findings is unclear but may be secondary to oxidative stress secondary to the significant decrease in antioxidant enzymes noted in affected testicles [53,54].

The effects of delta-9-tetrahydrocannabinol on semen parameters and sperm

A number of animal and human studies have reported that the most deleterious effects of marijuana on male reproductive capacity is its impact on semen parameters but this has not been adequately confirmed [36,42,46,47,55–57].

Sperm count and concentration

Studies in mice, rats, and dogs indicate that chronic use of recreational doses (3–12.5 mg/kg/day) of THC lead to decreased spermatogenesis and spermatogenic arrest [45,49,52,57]. Similarly, prior human studies, largely in men presenting for infertility evaluation, have also demonstrated reduction in sperm count and concentration after THC exposure [27,37,58]. In the Danish cohort described previously, weekly THC users had dramatically lower sperm counts than never users [47]. A case–control study of chronic weekly users (n = 12) and never users (n = 12) also found significantly lower sperm concentrations in the users but no change to their volume, motility, or morphology [59].

Morphology

THC can also affect sperm morphology. In a study of 229 Jamaican men presenting to establish primary care, 47% reported marijuana use of which, 21% recently used [60]. Recent and high-dose use had odds ratios (OR) of 2.6 and 4.3, respectively for asthenospermia whereas moderate quantity users had an OR of 3.4 for teratospermia [60]. A larger study of over 1900 men from infertile couples reported an OR of 1.94 for poor morphology in those with THC exposure in the prior 3 months [58].

Motility

Motility and metabolism are also diminished in the sperm after THC exposure. Activation of the sperm CB1 receptor has been shown to reduce sperm mitochondrial transmembrane potential [61] as well as limit the acrosomal reaction [62]. Whenever applied to sperm in vitro, THC caused an immediate decline in sperm mitochondrial oxygen consumption, though whole semen did have a protective effect [63]. In addition, when challenged with both recreational and therapeutic levels of THC, sperm motility and acrosomal reaction were decreased in a dose-dependent manner, with more pronounced effects in sperm that were weaker at baseline [36].

Sperm epigenetics

There is evidence of associations between THC exposure and altered DNA methylation of sperm in humans and rats [59]. Another study using a rat model noted that exposure to THC and nicotine alters sperm DNA methylation of active neurodevelopmental genes [64■■]. These studies suggest possible preconception paternal reproductive risks associated with cannabis use.

Clinical effects

Marijuana’s clinical effect on sexual function has been investigated in both preclinical models and humans, with general conclusion that THC increases sexual desire but may limit coital performance.

Erectile dysfunction

Marijuana use has been associated with erectile dysfunction; Elbendary et al. [65] demonstrated that chronic use can potentially induce early endothelial damage. In humans, a survey of 1203 men in 2006 found a significant association between marijuana use and inhibited orgasm (OR 1.76) but no increased risk of low sexual desire or excitement. Similar results were reported in a computer-assisted telephone survey of 8656 Australians where 8.7% used marijuana in the previous year: 1.5% reported daily use, 1.5% weekly use, and 5.8% less often than weekly use [66]. Daily use was associated with orgasmic disorders in men: inability to reach orgasm (OR 3.94), reaching orgasm too quickly (OR 2.68), or too slowly (OR 2.05) [66]. A prior systematic review and meta-analysis of five case–control studies found that erectile dysfunction was twice as high in marijuana users compared with controls [67].

Sexual function

The evidence supporting marijuana as an aphrodisiac is strong. Marijuana use is independently associated with increased sexual frequency, and daily use carries an increased likelihood of reporting two or more sexual partners in the previous year (OR 2.08 for men, 2.58 for women) [66,68]. When surveying 325 men visiting a marijuana dispensary, Bhambhvani et al. [69] found increased marijuana use was associated with increased erectile function, orgasm function, and sexual satisfaction, but no correlation with the type of marijuana product or delivery method.

GESTATIONAL EFFECTS OF MATERNAL MARIJUANA USE

Marijuana is the most common illicit drug used during pregnancy [70,71]. At present, the United States Surgeon General [72] and American College of Obstetricians and Gynecologists [71] advise pregnant and lactating patients to abstain from using marijuana. However, as the current safety data is insufficient, approximately half of marijuana users continue to use throughout pregnancy, especially for its anti-emetic properties, particularly in the first trimester during a developmentally vulnerable period. A recent study found that cannabis use disorder (CUD) in pregnancy increased from 2.8 to 6.9 per 1000 deliveries from 2001 to 2012 [73■]. The available published studies on marijuana exposure in pregnancy are limited but support some degree of developmental disruption associated with maternal marijuana use. Prenatal marijuana exposure has been associated with stillbirth, intrauterine growth restriction (IUGR), fetal neurodevelopmental consequences [74–81], and impaired offspring cognitive development [77,79,82]. However, most of the prenatal marijuana research that exists, including animal studies, was performed in the 1980s, reflecting marijuana exposure largely through smoking, with few reports studying doses and routes of administration that are comparable or relevant to contemporary use [83–87].

Pregnancy loss

Studies on preconception marijuana use and pregnancy loss are limited but largely do not support an association [28■■]. Overall, there does not appear to be any statistically significant association between prenatal marijuana use and stillbirth or miscarriage [77,88–90] but often studies that report an association are partially confounded by polysubstance use, especially co-use of tobacco and marijuana, or are under powered to detect such an association. A large case–control study by the Stillbirth Collaborative Research Network found that marijuana use was significantly associated with stillbirth (OR 2.34, 95% CI 1.13–4.81) but the effect was partly confounded by tobacco use [75].

Fetal and neonatal outcomes

In general, the literature is mixed but support an association between any prenatal marijuana used and an increased risk of preterm delivery [91–93], decreased birth weight ranging from an 84 to 256 g difference [88,91,94,95] and neonatal ICU (NICU) admissions [90,91]. There has not been strong evidence to support an increase of congenital anomalies from periconceptional marijuana use [9,90] but anomalies previously described involve the cardiac, genitourinary, gastrointestinal, and central nervous system [96–99].

Most recently, a large, population-based retrospective cohort (n = 661617) in Ontario, Canada found that any self-reported maternal marijuana use in pregnancy was significantly associated with an increased risk of preterm birth (RR 1.41, 95% CI 1.36–1.47), small for gestational age (RR 1.53, 95% CI, 1.45–1.61), placental abruption (RR 1.72, 95% CI, 1.54–1.92), transfer to neonatal intensive care (RR 1.40, 95% CI, 1.36–1.44), and 5 min Apgar score less than 4 (RR 1.28, 85% CI, 1.13–1.45) [100■]. Another recent, large retrospective study found that prenatal CUD was associated with greater odds of being small for gestational age (OR = 1.13, 95% CI = 1.07–1.2), preterm birth (OR = 1.06, 95% CI = 1.01–1.12), low birth weight (OR = 1.13, 95% CI = 1.07–1.20), and death within 1 year of birth (OR = 1.35, 95% CI = 1.12–1.62) [73■]. In particular, infants whose mothers were Hispanic had a higher likelihood of hospitalization and death and infants born to non-Hispanic black mothers had greater odds of being small for gestational age [73■].

Childhood outcomes

Currently, there is insufficient evidence to establish a strong association between prenatal marijuana exposure and later offspring outcomes including sudden infant death syndrome, cognition, academic achievement, and later substance abuse [101]. The literature consists largely of three main large, longitudinal cohort studies from 1970 to 2001 when marijuana was largely smoked and the potency of THC was lower [77,82,102,103]. Prior human studies have suggested that prenatal marijuana exposure may affect neurological development in offspring. In babies, an increased incidence of altered responses to visual stimuli, trembling, and high-pitched cry [104] have been reported. School-aged children have been shown a greater likelihood for gaps in problem-solving skills and memory, symptoms of depression and anxiety, and decreased attention span [105,106]. Adolescents haver a higher tendency towards delinquency and marijuana use by age 15 years old [79,107]. Most recently, Corsi et al. found an association between prenatal marijuana use and the incidence of autism spectrum disorder in the offspring [108■■], 4 per 1000 person-years among children with prenatal marijuana exposure compared with 2.42 among unexposed children (OR 1.51, 95% CI 1.17–1.96) [108■■]. Overall, the incidence of intellectual disability and learning disorders was higher in offspring exposed to marijuana prenatally but not statistically significant [108■■].

CONCLUSION

Marijuana is becoming more prevalent, especially among those of reproductive age, because of increasing accessibility, secondary to the shifting legal landscape and in parallel, the perception of safety. At this time, there is sufficient evidence of harm to warrant avoiding marijuana when attempting to conceive or when pregnant or breastfeeding. However, more research on the safety of marijuana is needed for healthcare providers to better counsel users regarding its effects on fertility or offspring.

KEY POINTS.

  • Chronic marijuana use can negatively affect female reproductive health and result in ovulatory dysfunction, menstrual cycle irregularity, and reproductive hormones.

  • Long-term marijuana use adversely affects male reproductive function and has been associated with testicular atrophy, low libido, sexual dysfunction, semen parameters, and reproductive hormone levels.

  • Prenatal marijuana use does not increase the risk of pregnancy loss but may be associated with preterm birth, decreased birth weight, and neonatal ICU admissions.

Footnotes

Conflicts of interest

There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

■ of special interest

■■ of outstanding interest

  • 1.United Nations Office on Drugs and Crime (UNODC). World Drug Report 2017 – United Nations Office on Drugs and Crime. 2017. [Google Scholar]
  • 2.Dunne C The effects of marijuana on female and male reproduction. BCMJ 2019; 61:282–285. [Google Scholar]
  • 3.Elsohly MA, Mehmedic Z, Foster S, et al. Changes in cannabis potency over the last 2 decades (1995–2014): analysis of current data in the United States. Biol Psychiatry 2016; 79:613–619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Smart R, Caulkins JP, Kilmer B, et al. Variation in marijuana potency & prices in a newly-legal market: evidence from 30 million marijuana sales in Washington State. Addiction 2017; 112:2167–2177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Sevigny EL. Is today’s marijuana more potent simply because it’s fresher? Drug Test Anal 2013; 5:62–67. [DOI] [PubMed] [Google Scholar]
  • 6.Kilmer B, Everingham SS, Cauclkins JP, et al. What America’s users spend on illegal drugs 2000–2010. prepared for the office of National Drug Control Policy. Washington, DC: Executive office of the president; 2014. [Google Scholar]
  • 7.Ayalon D, Nir I, Cordova T, et al. Acute effect of delta1-tetrahydrocannabinol on hypothalamo-pituitary-ovarian axis in the rat. Neuroendocrinology 1977; 23:31–42. [DOI] [PubMed] [Google Scholar]
  • 8.Chakravarty I, Sheth AR, Ghosh JJ. Effect of acute delta9-tetrahydrocannabinol treatment on serum luteinizing hormone and prolactin levels in adult female rats. Fertil Steril 1975; 26:947–948. [DOI] [PubMed] [Google Scholar]
  • 9.Dalterio SL, Mayfield DL, Bartke A. Effects of delta 9-THC on plasma hormone levels in female mice. Subst Alcohol Actions Misuse 1983; 4:339–345. [PubMed] [Google Scholar]
  • 10.Grant KS, Petroff R, Isoherranen N, et al. Marijuana use during pregnancy: pharmacokinetics and effects on child development. Pharmacol Ther 2018; 182:133–151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Brenner RM, Slayden OD. Molecular and functional aspects of menstruation in the macaque. Rev Endocr Metab Disord 2012; 13:309–318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Brenner RM, West NB, McClellan MC. Estrogen and progestin receptors in the reproductive tract of male and female primates. Biol Reprod 1990; 42:11–19. [DOI] [PubMed] [Google Scholar]
  • 13.Smith CG, Asch RH. Acute short-term and chronic effects of marijuana on the female primate reproductive function in marijuana effects on the endocrine and reproductive systems. NIDA Res Monogr 1984; 44:82–96. [PubMed] [Google Scholar]
  • 14.Asch RH, Smith CG, Siler-Khodr TM, Pauerstein CJ. Effects of Δ9-tetrahydrocannabinol during the follicular phase of the rhesus monkey (Macaca mulatta). J Clin Endocrinol Metab 1981; 52:50–55. [DOI] [PubMed] [Google Scholar]
  • 15.Asch RH, Smith CG. Effects of delta9-THC, the principal psychoactive component of marijuana, during pregnancy in the rhesus monkey. J Reprod Med 1986; 31:1071–1081. [PubMed] [Google Scholar]
  • 16.Besch NF, Smith CG, Besch PK, Kaufman RH. The effect of marihuana (delta-9-tetrahydrocannabinol) on the secretion of luteinizing hormone in the ovariectomized rhesus monkey. Am J Obstet Gynecol 1977; 128:635–642. [DOI] [PubMed] [Google Scholar]
  • 17. Ryan KS, Mahalingaiah S, Campbell LR, et al. The effects of delta-9-tetrahydrocannabinol exposure on female menstrual cyclicity and reproductive health in rhesus macaques. Fertil Steril Sci 2021. doi: 10.1016/j.xfss.2021.05.001. [in press] ■■ Ryan et al. demonstrated in rhesus macaques that daily THC exposure resulted in a dose response toward increased menstrual cycle length and basal follicle-stimulating hormone concentrations but a plateau of basal estradiol and lutenizing hormone concentrations suggesting ovulatory dysfunction.
  • 18.Smith CG, Besch NF, Smith RG, Besch PK. Effect of tetrahydrocannabinol on the hypothalamic-pituitary axis in the ovariectomized rhesus monkey. Fertil Steril 1979; 31:335. [DOI] [PubMed] [Google Scholar]
  • 19.Smith CG, Smith MT, Besch NF, et al. Effect of delta-nine-tetrahydrocannabinol (THC) on female reproductive function. In: Nahas GG, editor. Marihuana: chemistry, biochemistry and cellular effects, 2nd ed New York: Pergamon Press; 1980 [Google Scholar]
  • 20.Asch RH, Fernandez EO, Smith CG, Pauerstein CJ. Precoital single doses of delta9-tetrahydrocannabinol block ovulation in the rabbit. Fertil Steril 1979; 31:331–334. [PubMed] [Google Scholar]
  • 21.Tyrey L Delta-9-tetrahydrocannabinol suppression of episodic luteinizing hormone secretion in the ovariectomized rat. Endocrinology 1978; 102:1808–1814. [DOI] [PubMed] [Google Scholar]
  • 22.Dalterio S, Bartke A, Roberson C, et al. Direct and pituitary-mediated effects of delta9-THC and cannabinol on the testis. Pharmacol Biochem Behav 1978; 8:673–678. [DOI] [PubMed] [Google Scholar]
  • 23. Jordan T, Ngo B, Jones CA. The use of cannabis and perceptions of its effect on fertility among infertility patients. Hum Reprod Open 2020; 2020:hoz041. ■ This study suggests that cannabis use is common amongst infertility patients, and although there is concern for the potential impact of cannabis use on fertility, only 9% of past year marijuana users had been instructed by healthcare providers to cease cannabis use. Thus, healthcare providers should consider the benefits of counseling about cannabis cessation for those attempting to conceive.
  • 24.Reboussin BA, Wagoner KG, Sutfin EL, et al. Trends in marijuana edible consumption and perceptions of harm in a cohort of young adults. Drug Alcohol Depend 2019; 205:107660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Mueller BA, Daling JR, Weiss NS, Moore DE. Recreational drug use and the risk of primary infertility. Epidemiol 1990; 1:195–200. [DOI] [PubMed] [Google Scholar]
  • 26.Wise LA, Wesselink AK, Hatch EE, et al. Marijuana use and fecundability in a North American preconception cohort study. J Epidemiol Community Health 2018; 72:208–215. [DOI] [PubMed] [Google Scholar]
  • 27.Kasman AM, Thoma ME, McLain AC, Eisenberg ML. Association between use of marijuana and time to pregnancy in men and women: findings from the National Survey of Family Growth. Fertil Steril 2018; 109:866–871. [DOI] [PubMed] [Google Scholar]
  • 28. Mumford SL, Flannagan KS, Radoc JG, et al. Cannabis use while trying to conceive: a prospective cohort study evaluating associations with fecundability, live birth and pregnancy loss. Hum Reprod 2021; 36:1405–1415. ■■ Mumford et al. reported their secondary analysis of a prospective cohort study of women with a history of pregnancy loss studying if cannabis use preconception is associated with fecundability, live birth, and pregnancy loss. The study found that women with preconception cannabis use had reduced fecundability, but no association with pregnancy loss.
  • 29.Klonoff-Cohen HS, Natarajan L, Chen RV. A prospective study of the effects of female and male marijuana use on in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) outcomes. Am J Obstet Gynecol 2006; 194:369–376. [DOI] [PubMed] [Google Scholar]
  • 30.Nassan FL, Arvizu M, Minguez-Alarcon L, et al. Marijuana smoking and markers of testicular function among men from a fertility center. Hum Reprod 2019; 34:715–723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Center for Behavioral Health Statistics. Quality: 2016 National Survey on Drug Use and Health: detailed tables. Rockville, Maryland: Substance Abuse and Mental Health Services Administration; 2017. [Google Scholar]
  • 32.Aquila S, Guido C, Santoro A, et al. Human sperm anatomy: ultrastructural localization of the cannabinoid1 receptor and a potential role of anandamide in sperm survival and acrosome reaction. Anat Rec 2010; 293:298–309. [DOI] [PubMed] [Google Scholar]
  • 33.Schuel H, Burkman LJ, Lippes J, et al. Evidence that anandamide-signaling regulates human sperm functions required for fertilization. Mol Reprod Dev 2002; 63:376–387. [DOI] [PubMed] [Google Scholar]
  • 34.Rossato M, Popa FI, Ferigo M, et al. Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 2005; 90:984–981. [DOI] [PubMed] [Google Scholar]
  • 35.Jensen B, Chen J, Furnish T, Wallace M. Medical marijuana and chronic pain: a review of basic science clinical evidence. Curr Pain Headache Rep 2015; 19:50. [DOI] [PubMed] [Google Scholar]
  • 36.Hembree WC 3rd, Nahas GG, Zeidenberg P, et al. Changes in human spermatozoa associated with high dose marihuana smoking. Adv Biosci 1978; 22–23:429–439. [DOI] [PubMed] [Google Scholar]
  • 37.Close CE, Roberts PL, Berger RE. Cigarettes, alcohol and marijuana are related to pyospermia in infertile men. J Urol 1990; 144:900–903. [DOI] [PubMed] [Google Scholar]
  • 38.El-Gothamy Z, el Samahy M. Ultrastructure sperm defects in addicts. Fertil Steril 1992; 57:699–702. [DOI] [PubMed] [Google Scholar]
  • 39.Cone EJ, Johnson RE, Moore JD, et al. Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects. Pharmacol Biochem Behav 1986; 24:1749–1754. [DOI] [PubMed] [Google Scholar]
  • 40.Vescovi PP, Pedrazzoni M, Michelini M, et al. Chronic effects of marihuana smoking on luteinizing hormone, follicle-stimulating hormone and prolactin levels in human males. Drug Alcohol Depend 1992; 30:59–63. [DOI] [PubMed] [Google Scholar]
  • 41.Murphy LL, Steger RW, Smith MS, Bartke A. Effects of delta-9-tetrahydrocannabinol, cannabinol and cannabidiol, alone and in combinations, on luteinizing hormone and prolactin release and on hypothalamic neurotransmitters in the male rat. Neuroendocrinology 1990; 52:316–321. [DOI] [PubMed] [Google Scholar]
  • 42.Kolodny RC, Masters WH, Kolodner RM, Toro G. Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl J Med 1974; 290:872–874. [DOI] [PubMed] [Google Scholar]
  • 43.Rajanahally S, Raheem O, Rogers M, et al. The relationship between marijuana and male infertility, sexual health, and neoplasm: a systematic review. Andrology 2019; 7:139–147. [DOI] [PubMed] [Google Scholar]
  • 44.List A, Nazar B, Nyquist S, Harclerode J. The effects of delta9-tetrahydrocannabinol and cannabidiol on the metabolism of gonadal steroids in the rat. Drug Metab Dispos 1977; 5:268–272. [PubMed] [Google Scholar]
  • 45.Banerjee A, Singh A, Srivastava P, et al. Effects of chronic bhang (marijuana) administration on the reproductive system of male mice. Birth defects Res B Dev Reprod Toxicol 2011; 92:195–205. [DOI] [PubMed] [Google Scholar]
  • 46.Dalterio S, Badr F, Bartke A, Mayfield D. Cannabinoids in male mice: effects on fertility and spermatogenesis. Science 1982; 216:315–316. [DOI] [PubMed] [Google Scholar]
  • 47.Gundersen TD, Jørgensen N, Andersson AM, et al. Association between use of marijuana and male reproductive hormones and semen quality: a study among 1,215 healthy young men. Am J Epidemiol 2015; 182:473–481. [DOI] [PubMed] [Google Scholar]
  • 48.Thistle JE, Graubard BI, Braunlin M, et al. Marijuana use and serum testosterone concentrations among U.S. males. Andrology 2017; 5:732–738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Dixit VP, Sharma VN, Lohlya NK. The effect of chronically administered marijuana extract on the testicular function of mice. Eur J Pharmacol 1974; 26:111–114. [DOI] [PubMed] [Google Scholar]
  • 50.Harclerode J Endocrine effects of marijuana in the male: preclinical studies. NIDA Res Monogr 1984; 44:46–64. [PubMed] [Google Scholar]
  • 51.Fujimoto GI, Morrill GA, O’Connell ME, et al. Effects of cannabinoids given orally and reduced appetite on the male rat reproductive system. Pharmacology 1982; 24:303–313. [DOI] [PubMed] [Google Scholar]
  • 52.Dixit VP, Gupta CL, Agrawal M. Testicular degeneration and necrosis induced by chronic administration of marijuana extract in dogs. Endokrinologie 1977; 69:299–305. [PubMed] [Google Scholar]
  • 53.Mandal TK, Das NS. Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of antioxidant enzyme systems. Toxicol Ind Health 2010; 26:11–23. [DOI] [PubMed] [Google Scholar]
  • 54.Alagbonsi IA, Olayaki LA, Salman TM. Melatonin and vitamin C exacerbate Cannabis sativa-induced testicular damage when administered separately but ameliorate it when combined in rats. J Basic Clin Physiol Pharmacol 2016; 27:277–287. [DOI] [PubMed] [Google Scholar]
  • 55.Issidorides MR. Observations in chronic hashish users: nuclear aberrations in blood and sperm and abnormal acrosomes in spermatozoa. In: Nahas GG, Paton W, editors. Marihuana: biological effects. New York: Pergamon; 1979. pp. 377–388. [DOI] [PubMed] [Google Scholar]
  • 56.Payne KS, Mazur DJ, Hotaling JM, Pastuszak AW. Marijuana and male fertility: a systematic review. J Urol 2019; 202:674–681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Huang HFS, Nahas GG, Hembree WC. Effects of marihuana inhalation on spermatogeneiss of the rat. Adv Biosci 1978; 22–23:419–427. [DOI] [PubMed] [Google Scholar]
  • 58.Pacey AA, Povey AC, Clyma JA, et al. Modifiable and nonmodifiable risk factors for poor sperm morphology. Hum Reprod 2014; 29:1629–1636. [DOI] [PubMed] [Google Scholar]
  • 59.Murphy SK, Itchon-Ramos N, Visco Z, et al. Cannabinoid exposure and altered DNA methylation in rat and human sperm. Epigenetics 2018; 13:1208–1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Carroll K, Pottinger AM, Wynter S, DaCosta V. Marijuana use and its influence on sperm morphology and motility: identified risk for fertility among Jamaican men. Andrology 2020; 8:136–142. [DOI] [PubMed] [Google Scholar]
  • 61.Barbonetti A, Vassallo MR, Fortunato D, et al. Energetic metabolism and human sperm motility: impact of CB1 receptor activation. Endocrinology 2010; 151:5882–5892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Rossato M, Ion Popa F, Ferigo M, et al. Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 2005; 90:984–991. [DOI] [PubMed] [Google Scholar]
  • 63.Badawy ZS, Chohan KR, Whyte DA, et al. Cannabinoids inhibit the respiration of human sperm. Fertil Steril 2009; 91:2471–2476. [DOI] [PubMed] [Google Scholar]
  • 64. Schrott R, Rajavel M, Acharya K, et al. Sperm DNA methylation altered by THC and nicotine: vulnerability of neurodevelopmental genes with bivalent chromatin. Sci Rep 2020; 10:16022. ■■ Schrott et al. demonstrated that reduced representation bisulfite sequencing data from sperm of rats exposed to tetrahydrocannabinol via oral gavage showed seven neurodevelopmentally active genes that were significantly differentially methylated versus controls that included autism candidates.
  • 65.Elbendary MA, El-Gamal OM, Salem KA. Analysis of risk factors for organic erectile dysfunction in Egyptian patients under the age of 40 years. J Androl 2009; 30:520–524. [DOI] [PubMed] [Google Scholar]
  • 66.Smith AMA, Ferris JA, Simpson JM, et al. Cannabis use and sexual health. J Sex Med 2010; 7(2 Pt 1):787–793. [DOI] [PubMed] [Google Scholar]
  • 67.Pizzol D, Demurtas J, Stubbs B, et al. Relationship between marijuana use and erectile dysfunction: a systematic review and meta-analysis. Am J Mens Health 2019; 13:1557988319892464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Sun AJ, Eisenberg ML. Association between marijuana use and sexual frequency in the United States: a population-based study. J Sex Med 2017; 14:1342–1347. [DOI] [PubMed] [Google Scholar]
  • 69.Bhambhvani HP, Kasman AM, Wilson-King G, Eisenberg ML. A survey exploring the relationship between marijuana use characteristics and sexual function in men. Sex Med 2020; 8:436–445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Martin CE, Longinaker N, Mark K, et al. Recent trends in treatment admission for marijuana use during pregnancy. J Addict Med 2015; 9:99–104. [DOI] [PubMed] [Google Scholar]
  • 71.Marijuana use during pregnancy, lactation. Committee Opinion No. 637. American College of Obstetricians and Gynecologists. Obstet Gynecol 2015; 126:234–238. [DOI] [PubMed] [Google Scholar]
  • 72.U.S. Surgeon General’s Advisory: Marijuana use and the developing brain. Available at: https://www.hhs.gov/surgeongeneral/reports-and-publications/addiction-and-substance-misuse/advisory-on-marijuana-use-and-developing-brain/index.html. (Accessed 26 May 2021)
  • 73. Shi Y, Zhu B, Liang D. The association between prenatal marijuana use disorder and neonatal outcomes. Addiction 2021. doi: 10.1111/add.15467. [Epub ahead of print] ■ Shi et al. studied 4.83 million mothers with singleton pregnancies from 2001 to 2012 and found that prenatal cannabis use disorder is associated with increased odds of major adverse neonatal outcomes including small for gestational age, preterm birth, low birth weight, and death within 1 year of birth.
  • 74.Alhusen JL, Lucea MB, Bullock L, Sharps P. Intimate partner violence, substance abuse and adverse neonatal outcomes among urban women. J Pediatr 2013; 163:471–476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Varner MW, Silver RM, Rowland Hogue CJ, et al. Association between stillbirth and illicit drug use and smoking drug in pregnancy. Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network. Obstet Gynecol 2014; 123:113–125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Hayatbakhsh MR, Flenady VJ, Gibbons KS, et al. Birth outcomes associated with cannabis use before and during pregnancy. Pediatr Res 2012; 71:215–219. [DOI] [PubMed] [Google Scholar]
  • 77.El Marroun H, Tiemeier H, Steegers EA, et al. Intrauterine cannabis exposure affects fetal growth trajectories: the Generation R Study. J Am Acad Child Adolesc Psychiatry 2009; 48:1173–1181. [DOI] [PubMed] [Google Scholar]
  • 78.Hurd YL, Wang X, Anderson V, et al. Marijuana impairs growth in midgestation fetuses. Neurotoxicol Teratol 2005; 27:221–229. [DOI] [PubMed] [Google Scholar]
  • 79.Day NL, Goldschmidt L, Thomas CA. Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14 years. Addiction 2006; 101:1313–1322. [DOI] [PubMed] [Google Scholar]
  • 80.Fernandez-Ruiz JJ, Berrendero F, Hernandez ML, et al. Role of endocannabinoids in brain development. Life Sci 1999; 65:725–736. [DOI] [PubMed] [Google Scholar]
  • 81.Goldschmidt L, Richardson GA, Wilford J, Day NL. Prenatal marijuana exposure and intelligence test performance at age 6. J Am Acad Child Adolesc Psychiatry 2008; 47:254–263. [DOI] [PubMed] [Google Scholar]
  • 82.Fried PA, Watkinson B, Gray R. Differential effects on cognitive functioning in 9- to 12- year olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol 1998; 20:293–306. [DOI] [PubMed] [Google Scholar]
  • 83.Mehmedic Z, Chandra S, Slade D, et al. Potency trends of Delta9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 1997. J Forensic Sci 2010; 55:1209–1217. [DOI] [PubMed] [Google Scholar]
  • 84.Bailey JR, Cunny HC, Paule MG, Slikker W Jr. Fetal disposition of delta 9-tetrahydrocannabinol (THC) during late pregnancy in the rhesus monkey. Toxicol Appl Pharmacol 1987; 90:315–321. [DOI] [PubMed] [Google Scholar]
  • 85.Fisher SE, Atkinson M, Chang B. Effect of delta-9-tetrahydrocannabinol on the in vitro uptake of alpha-amino isobutyric acid by term human placental slices. Pediatr Res 1987; 21:104–107. [DOI] [PubMed] [Google Scholar]
  • 86.Abel EL. Marihuana, tobacco, alcohol and reproduction. 1st ed. Boca Raton (FL): CRC Press; 1983. 31–33. [Google Scholar]
  • 87.Hingson R, Alpert JJ, Day N, et al. Effect of maternal drinking and marijuana use on fetal growth and development. Pediatrics 1982; 70:539–546. [PubMed] [Google Scholar]
  • 88.Fergusson DM, Horwood LJ, Northstone K, et al. Maternal use of cannabis and pregnancy outcome. BJOG 2002; 109:21–27. [DOI] [PubMed] [Google Scholar]
  • 89.Linn S, Schoenbaum SC, Monson RR, et al. The association of marijuana use with outcome of pregnancy. Am J Public Health 1983; 73:1161–1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90.Warshak CR, Regan J, Moore B, et al. Association between marijuana use and adverse obstetrical and neonatal outcomes. J Perinatol 2015; 35:991–995. [DOI] [PubMed] [Google Scholar]
  • 91.Gunn JK, Rosales CB, Center KE, et al. Prenatal exposure to cannabis and maternal and child health outcomes: a systematic review and meta-analysis. BMJ Open 2016; 6:e009986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Dekker GA, Lee SY, North RA, et al. Risk factors for preterm birth in an international prospective cohort of nulliparous women. PlosS One 2012; 7:e39154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.Leemaqz SY, Dekker GA, McCowan LM, et al. Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications. Reprod Toxicol 2016; 62:77–86. [DOI] [PubMed] [Google Scholar]
  • 94.Janisse JJ, Bailey BA, Ager J, Sokol RJ. Alcohol, tobacco, cocaine, and marijuana use: relative contributions to preterm delivery and fetal growth restriction. Subst Abus 2014; 35:60–67. [DOI] [PubMed] [Google Scholar]
  • 95.Gray TR, Eiden RD, Leonard KE, et al. Identifying prenatal cannabis exposure and effects of concurrent tobacco exposure on neonatal growth. Clin Chem 2010; 56:144–1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96.van Gelder MMHJ, Donders RT, Devine O, et al. Using Bayesian models to assess the effects of under-reporting cannabis use on the association with birth defects: National Birth Defects Prevention Study. Paediatr Perinat Epidemiol 2014; 28:424–433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97.Williams LJ, Correa A, Rasmussen S. Birth defects research (part A). Clin Mol Teratol 2004; 70:59–64. [DOI] [PubMed] [Google Scholar]
  • 98.Shaw GM, Velie EM, Morland KB. Parental recreational drug use and risk for neural tube defects. Am J of Epidemiology 1996; 144:1155–1160. [DOI] [PubMed] [Google Scholar]
  • 99.Forrester MB, Mertz RD. Risk of selected birth defects with prenatal illicit drug use, Hawaii. J Toxicol Environ Health A 2007; 70:7–18. [DOI] [PubMed] [Google Scholar]
  • 100. Corsi DJ, Walsh L, Weiss D, et al. Association between self-reported prenatal marijuana use and maternal, perinatal, and neonatal outcomes. JAMA 2019; 322:145–152. ■ Corsi et al. studied 661 617 women and found that self-reported cannabis use was significantly associated with an increased risk of preterm birth and also greater frequency of small for gestational age neonates, placental abruption, transfer to neonatal intensive care and a 5-min Apgar score less than 4.
  • 101.National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Population Health and Public Health Practice; Committee on Health Effects of Marijuana: the Current State of Evidence and Recommendations for Research. Therapeutic effects of cannabis and cannabinoids. Washington, DC, USA: National Academies Press; 2017. 4. Available at: https://wwww.ncbi.nlm.nih.gov/books/NBK425767/ (Accessed 26 May 2021). [PubMed] [Google Scholar]
  • 102.Fried PA. The ottawa prenatal prospective study (OPPS): Methodological issues and findings - it’s easy to throw the baby out with the bath water. Life Sci 1995; 56:2159–2168. [DOI] [PubMed] [Google Scholar]
  • 103.Richardson KA, Hester AK, McLemore GL. Prenatal cannabis exposure - the ‘first hit’ to the endocannabinoid system. Neurotoxicol Teratol 2016; 58:5–14. [DOI] [PubMed] [Google Scholar]
  • 104.de Moraes Barros MC, Guinsburg R, Mitsuhiro S, et al. Neurobehavioral profile of healthy full-term newborn infants of adolescent mothers. Early Hum Dev 2008; 84:281–287. [DOI] [PubMed] [Google Scholar]
  • 105.Leech SL, Larkby CA, Day R, Day NL. Predictors and correlates of high levels of depression and anxiety symptoms among children at age 10. J Am Acad Child Adolesc Psychiatry 2016; 45:223–230. [DOI] [PubMed] [Google Scholar]
  • 106.Goldschmidt L, Day NL, Richardson GA. Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol Teratol 2000; 22:325–336. [DOI] [PubMed] [Google Scholar]
  • 107.Day NL, Leech SL, Goldschmidt L. The effects of prenatal marijuana exposure on delinquent behaviors are mediated by measures of neurocognitive functioning. Neurotoxicol Teratol 2011;33:129–136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 108. Corsi DJ, Donelle J, Sucha E, et al. Maternal cannabis use in pregnancy and child neurodevelopmental outcomes. Nat Med 2020; 26:1536–1540. ■■ Corsi et al, reported on all live births in Ontario, Canada between 2007 and 2012 and found an association between maternal cannabis use in pregnancy and the incidence of autism spectrum disorder in the offspring. There was also an increased incidence of intellectual disability and learning disorders in offspring born to mothers who used cannabis prenatally.

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