Cannabis and Male Fertility: A Systematic Review (2024)

The publisher's final edited version of this article is available at J Urol

Count and Concentration

Cannabis use is strongly associated with reductions in sperm count and concentration in animal and human studies. Decreased epididymal sperm concentrations were observed in mature male rats exposed to 16 puffs per day of marijuana, comparable to the recreational level in humans, for 75 days.⁹ This effect was replicated in a study in which 3 to 6 mg/kg of the Cannabis sativa derivative bhang was administered in adult male mice, which demonstrated a significantly depressed sperm count (p <0.05).¹⁰ Echoing these observations in rodents, daily administration of cannabis at a rate of 12.5 mg/kg for 30 days in dogs was associated with complete spermatogenesis arrest.¹¹

Human studies have shown similar findings. In 20 chronic marijuana users who smoked marijuana at least 4 days per week for 6 months those who smoked 10 or more times per week had a significantly lower average ± SD sperm count than men who smoked 5 to 9 marijuana cigarettes per week (26.6 ± 7.3 vs 67.9 ± 6.3 million per ml, p <0.01).¹² This suggests an inverse relationship between marijuana use and sperm count. A Danish cohort study on marijuana use in 1,215 participants revealed similar changes.¹³ Men who reported using marijuana more than once per week had a 28% lower sperm concentration and a 29% lower sperm count than men who had never used marijuana. In a study in which 16 chronic marijuana smokers were exposed to 4 weeks of high dose marijuana the time to a reduced sperm count was 5 to 6 weeks after initiating marijuana use.¹⁴ In human and animal models cannabis has shown strong links to reduced sperm count and concentration which may be linked to arrested spermatogenesis. Future work is needed to elucidate causal mechanisms.

Morphology

Cannabis use also appears to induce considerable morphological changes in sperm. In a 1978 study Zimmerman et al treated male mice for 5 consecutive days with intraperitoneal injections of the marijuana components THC, cannabinoid or cannabinol.¹⁵ On microscopy 35 days after exposure mice treated with THC and cannabinol had a significantly higher incidence of abnormal morphology than the control group, such as banana-shaped, amorphous, folded or hookless heads. In another study rats given inhaled marijuana demonstrated similar changes in sperm with increased detachment of sperm heads from tails.⁹ These findings were expanded by a prospective, 1,700 unmatched case reference study of men in the United Kingdom presenting at a total of 14 fertility clinics.¹⁶ Men who had used cannabis in the 3 months prior to collection of a sem*n sample and were younger than 30 years were more likely to be in the category of abnormal sperm morphology, defined as less than 4% normal sperm morphology (OR 1.94, 95% CI 1.05–3.60).

Despite morphological changes the research suggests that cannabis does not induce chromosome breakage in sperm. Generoso et al administered 50 mg/kg THC 5 times per week for 6 weeks in 498 male mice.¹⁷ After mating them with females no increase was observed in fetal dominant lethal mutations or heritable translocations over those in controls. These findings were supported by a study by Berryman et al, who found no THC induced increase in pre-implantation loss, fetal mortality or the mutation index in fetuses fathered by male mice chronically dosed with THC.¹⁸ In animal and human models evidence suggests that cannabis induces morphological changes in sperm while genetic material is preserved.

Motility and Energy Metabolism

The most extensive body of evidence for cannabis related alterations to sperm is for sperm motility. Whan et al noted spermatotoxic effects of THC by incubating sperm with THC at therapeutic doses, similar to concentrations shown to relieve pain or reduce spasticity in humans with multiple sclerosis (0.032 μM) and recreational concentrations (4.8 and 0.32 μM) for 3 hours, and then measuring motility by computer assisted sem*n analysis.¹⁹ The sperm were divided into fractions of 90% with the best fertilizing potential and 45% with a poorer subpopulation. Compared to controls the 45% fraction showed 28% reduced motility at 0.032 μM THC (p=0.004) and 56% reduced motility at 4.8 μM THC (p=0.01). The 90% fraction showed no significant difference in motility at 0.032 μM (p=0.80) but a 28% decrease in motility at 4.8 μM (p <0.001). Therapeutic and recreational THC concentrations also resulted in reduced straight line velocity. A similar decrease in sperm motility was seen in an analysis of sem*n samples from 16 healthy, chronic marijuana users after 4 weeks of high dose marijuana.¹⁴

Barbonetti et al elucidated the mechanism of these findings by establishing a link between CB1 and sperm mitochondrial activity.²⁰ In sperm incubated with the CB1 receptor agonist Met-AEA a significant reduction was observed in mitochondrial transmembrane potential. When the sperm were placed under glycolysis blockade, causing them to switch oxidative phosphorylation, the introduction of Met-AEA abolished sperm motility.

The link between cannabis and sperm mitochondrial dysfunction was furthered by Badawy et al, who added THC to sem*n and measured the oxygen concentration as a marker of respiration.²¹ Upon the addition of THC mitochondrial respiration immediately declined and was concentration dependent in effect. The results were much more pronounced in washed sperm than in neat sem*n, suggesting that seminal plasma contains some protective factors.

These various investigations suggest that through the action of cannabis on the CB1 receptor the mitochondrial activity of sperm is reduced and as a result motility is significantly impaired. Although Met-AEA and THC administration in the laboratory has helped map potential pathways, to our knowledge it is not known whether these effects are fully replicated in the male testes. Future testing should be done to explore whether mitochondrial impairment is present in the sem*n of chronic cannabis users.

Viability

Cannabis also has a detrimental effect on sperm viability. Rossato et al incubated sem*n samples with the endocannabinoid AEA at varying concentrations and found that viability was decreased in a dose dependent manner at supraphysiological AEA concentrations.²²

Reduced sperm viability related to cannabis has also been investigated using the highly specific CB1 receptor antagonist rimonabant (SR141716). Cobellis et al found that adding a micromolar concentration of rimonabant induced a small but significant increase in the number of viable spermatozoa.²³ Aquila et al reported similar findings with 1 and 10 nM concentrations of rimonabant increasing sperm viability with no further viability changes observed at higher concentrations.⁴ While the cannabinoid system has clear links to sperm viability, future work should be done to confirm these findings with exogenous cannabinoids as well as in the in vivo setting.

Fertilization Capacity

Research suggests that the cannabinoid signaling pathway may be involved in inhibiting sperm capacitation and activation. Using high performance liquid chromatography Schuel et al observed that high levels of AEA are present in seminal plasma and in progressively decreasing amounts in oviductal and follicular fluid, indicating that sperm are exposed to progressively decreasing AEA levels along the entire fertilization path.^24,25 The authors speculated that high AEA levels maintain sperm in a quiescent state and the decrease in AEA levels which occurs in the fertilization environment enables sperm to become activated. These data suggest that increases in cannabinoid levels may interfere with sperm activation and may be especially pertinent in the female reproductive tract, which the sperm depend on for tightly regulated AEA levels to maintain proper function.

Rossato et al reported that AEA inhibits the capacitation induced acrosome reaction of human sperm after incubation in capacitating medium.²² Using boar sperm Maccarrone et al found that Met-AEA reduced sperm capacitation in a time dependent manner.²⁶ They also noted that this effect was mediated by the CB1 receptor since when rimonabant, which blocks CB1, was added, Met-AEA produced no change in capacitation.

Schuel et al used the cannabinoid agonist AM-365 to identify concentration dependent stimulation and inhibition of sperm hyperactivated motility, which is a state needed for sperm to reach the egg surface and which assists with penetration of the zona pellucida.²⁵ In addition, they found that AM-365 administration completely inhibited the acrosomal modifications needed to prepare for zona pellucida binding and AM-365 decreased tight binding of sperm to the zona pellucida, which is needed for fertilization, by 49% (p <0.001). Whan et al used THC with similar results.¹⁹ They reported that for sperm undergoing artificial induction of the acrosome reaction THC resulted in 57% inhibition of the acrosome reaction (p <0.001).

Current work suggests that the endocannabinoid system is intimately linked to the fertilization process in the male and female reproductive tracts. Given the well described inhibitory effects, cannabis is likely to have negative impacts on fertilizing potential.

Follicle Stimulating Hormone

Relatively few studies have focused on cannabis and FSH levels, and most have observed no effect. Cone et al found no significant change in FSH levels in 4 healthy males with a history of frequent marijuana use before and after 2 marijuana cigarettes per day for 3 consecutive days.²⁷ This finding was replicated by Wenger et al, who injected THC in the third cerebral ventricle of adult male rats and subsequently observed no alteration in serum FSH levels with time.²⁸ Vescovi et al observed that cannabis did not alter the response of FSH to gonadotropin-releasing hormone in 10 male chronic marijuana users given gonadotropin-releasing hormone intravenously.²⁹ A depression in FSH levels was observed only by Kolodny et al, who compared plasma hormone levels among 11 men who used 5 to 9 marijuana cigarettes per week, 9 who used 10 or more marijuana cigarettes per week and normal controls.¹² The group using 10 or more cigarettes per week had significantly lower FSH (p <0.01).

Based on current studies, FSH may not be affected by cannabis except perhaps in the limited case of heavy chronic use. Human studies to date have been limited in suggestive power due to the small cohort sizes, leaving considerable room for further validation with larger sample size investigations.

Luteinizing Hormone

In human and animal models LH is consistently lowered by cannabis.^27–30 In the single exception Kolodny et al did not observe any significant difference in plasma LH levels between men who smoked 5 to 9 marijuana cigarettes per week and men who smoked 10 or more per week.¹² However, the variation in marijuana use levels in this study may have been insufficient to induce LH variations.

The relationship between cannabis and LH was strengthened in a study by Wenger et al, who used polyclonal antibodies against CB1 and CB2 to localize individual cells expressing cannabinoid receptors.³¹ The CB1 receptor was found in the anterior pituitary in LH secreting gonadotrophic cells. Wenger et al reaffirmed these results after administering AEA to wild-type and CB1 knockout mice, which revealed decreased LH secretion in the wild-type mice but unchanged LH levels in the CB1 knockout mice.³² As is the case with FSH related investigations, understanding how cannabis impacts LH would be improved by larger randomized, controlled trials in human subjects.

Testosterone

The reported effect of cannabis on serum testosterone levels is widely variable across current studies. In an early work in 20 chronic marijuana users Kolodny et al found a significant reduction in testosterone levels between chronic and never marijuana users (p <0.001).¹² The average plasma testosterone level in the control group was 742 ± 29 ng/ml, while levels were 503 ± 40 and 309 ± 34 ng/ml in the 5 to 9 and the 10 or more marijuana cigarettes a week groups, respectively (p <0.005). Serum testosterone reduction in the setting of cannabis use has also been observed in several animal models.^10,32 In rats dosed acutely with THC at 10 mg/kg, a significant depression in testicular testosterone synthesis was observed. An even larger effect on testicular testosterone synthesis was observed in rats dosed chronically with THC at 2 mg/kg.³³

The evidence that cannabis depresses testosterone levels relies heavily on animal studies. In contrast to findings in animals, most human studies support the conclusion that testosterone levels are not significantly changed by cannabis use. A 1974 study by Mendelson et al in 27 chronic marijuana users who were administered marijuana for 21 days showed no significant changes in plasma testosterone levels.³⁴ In a 1986 study of 4 male chronic marijuana users given 2 marijuana cigarettes per day depressed free testosterone levels were observed but the levels did not significantly differ from baseline.²⁷ In a later study free testosterone levels were compared in 41 normal controls and in 66 Pakistani men who smoked cannabis daily or regularly consumed cannabis tea.³⁵ No significant difference was observed in plasma testosterone levels between the cannabis users and the normal controls. Although sample size was limited in these early human studies, they suggest that cannabis consumption does not significantly alter testosterone levels.

It is only recently that large cohort studies of cannabis users have been possible. To date these studies have continued the trend of presenting conflicting or inconclusive evidence on the link between cannabis use and testosterone levels.

The first large cohort study on the effects of cannabis use was performed by Gundersen et al in 2015 using a registry of 1,215 Danish men undergoing compulsory medical examination to determine fitness for service.¹³ Testosterone levels were 7% higher in self-reported marijuana smokers than in nonusers. This was within the same range of testosterone elevation observed in cigarette smokers in the cohort. The authors cautioned that the increased testosterone levels in marijuana users could not be separated from the effect of tobacco smoking alone.

A second major cohort study was done in 2017 by Thistle et al.³⁶ They used data on 1,577 American men using data from the 2011 to 2012 United States National Health and Nutrition Survey with several novel outcomes. No difference was observed in serum testosterone levels between ever and never users of marijuana. However, serum testosterone levels showed an inverse association with time since the last regular use of marijuana, and since the last marijuana use (p for trend 0.02 and <0.01, respectively). This indicated that recency rather than frequency of use may have the strongest relationship with serum testosterone levels. Additional large, population based samples are needed to clarify currently conflicting reported effects of cannabis on testosterone levels.

TESTICULAR SIZE CHANGES

Current research suggests a link between cannabis and testicular atrophy, although this evidence relies largely on animal models. Studies in mice and rats have recorded significant dose dependent reductions in prostate and seminal vesicle weight.^10,37–39 A study of dogs administered daily cannabis extract (12.5 mg/kg body weight) recorded testicular degeneration and necrosis after only 30 days of exposure.¹¹

In a histological examination of the testes of mice exposed to cannabis Mandal and Das found fewer spermatogonia as well as basem*nt membrane damage, scant cytoplasm and shrunken nuclei.⁴⁰ They also observed a reduction in seminiferous tubule diameter. Fortunately complete recovery of spermatogenesis and testicular cell function was seen 45 days after ceasing cannabis use, although testicular weight and seminiferous tubule size were not completely restored at that time. The authors speculated that testicular damage may be due to oxidative stress as a result of finding a significant decrease in antioxidant enzymes in affected testicl*s. This hypothesis was furthered by the work of Alagbonsi et al, who found that testicular damage induced by Cannabis sativa in rats was ameliorated by administering an antioxidant combination of melatonin and vitamin C.⁴¹

Banerjee et al reported that cannabis has direct effects on seminiferous tubule function which is not mediated simply by hormone levels.¹⁰ The seminiferous tubules express LH receptor and fatty acid amide hydrolase, which has a pivotal role in modulating sperm motility, capacitation and the acrosome reaction. Western blot of LH receptor and fatty acid amide hydrolase after low and high dose administration of bhang showed significant reductions in the expression of each protein (p <0.05).

Animal models present clear evidence of testicular atrophy after prolonged and consistent exposure to cannabis, an effect which is likely to be largely reversible. Current research indicates that this effect is at least in part due to direct damage to the seminiferous tubules, which may be mediated by oxidative stress. Future work is needed to better understand how these findings carry over into human models, particularly in terms of identifying the quantity and the duration of cannabis exposure which could produce changes equivalent to those observed in animal studies to date.

SEXUAL FUNCTION

Cannabis, which has been used as an aphrodisiac since ancient times, was anecdotally described to enhance sexual performance and enjoyment.⁴² In interview data on 800 chronic cannabis users collected by Kolodny et al 83% reported enhanced sexual pleasure while using cannabis.⁴³ A recent investigation by Androvicova et al validated these results by showing that cannabis intoxication increased activation of the right nucleus accumbens upon presentation of erotic stimuli, leading the authors to conclude that cannabis may help in the treatment of hypoactive sexual desire.⁴⁴

In contrast to these findings, animal studies demonstrated reduced libido after acute and chronic cannabis administration. Using 5 mg/kg THC Murphy et al found that 30 minutes after THC injection the percent of male rats showing copulatory behavior with sexually receptive females was significantly diminished.⁴⁵ Using 10 mg/kg THC Dhawan and Sharma found that after 30 consecutive days of THC administration male rats showed reduced copulatory and mounting behaviors without decreased motor activity levels overall.⁴⁶

Supporting the findings in animal models, research has also tied cannabis to sexual dysfunction. Aversa et al observed that of 64 men evaluated for ED complaints 78% with organic ED admitted to frequently smoking cannabis in contrast to only 3% with nonorganic ED.⁴⁷ The group demonstrated that impaired epithelium dependent vasodilation occurred more frequently in individuals with organic ED, leading to the conclusion that cannabis likely induces ED through early endothelial damage.

Strengthening the evidence that the cannabinoid system is linked to erectile capacity, Succu et al found that the CB1 receptor blocker rimonabant induced erection in rats when injected into the paraventricular nucleus.⁴⁸ Melis et al followed up on these results and reported that the mechanism is likely mediated by neuronal nitric oxide synthase activation by rimonabant.⁴⁹

On the whole, current research points to a paradoxical effect of cannabis on sexual function. While short-term libido is augmented, the ability to achieve erection appears to be diminished. Future research is needed to elucidate the causative effects.

Suppl Appendix 1

Suppl Appendix 2

The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number.

No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article.

1. Sharma P, Murthy P and Bharath MM: Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry2012; 7: 149. [PMC free article] [PubMed] [Google Scholar]

3. Pertwee RG: The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol2008; 153: 199. [PMC free article] [PubMed] [Google Scholar]

4. Aquila S, Guido C, Santoro Aet al.: Human sperm anatomy: ultrastructural localization of the cannabinoidl receptor and a potential role of anandamide in sperm survival and acrosome reaction. Anat Rec (Hoboken)2010; 293: 298. [PubMed] [Google Scholar]

5. Jensen B, Chen J, Furnish Tet al.: Medical marijuana and chronic pain: a review of basic science and clinical evidence. Curr Pain Headache Rep2015; 19: 50. [PubMed] [Google Scholar]

6. Agirregoitia E, Carracedo A, Subiran Net al.: The CB(2) cannabinoid receptor regulates human sperm cell motility. Fertil Steril2010; 93: 1378. [PubMed] [Google Scholar]

7. Noel C: Evidence for the use of “medical marijuana” in psychiatric and neurologic disorders. Ment Health Clin2018; 7: 29. [PMC free article] [PubMed] [Google Scholar]

8. Bari M, Battista N, Pirazzi Vet al.: The manifold actions of endocannabinoids on female and male reproductive events. Front Biosci (Landmark Ed)2011; 16: 498. [PubMed] [Google Scholar]

9. Huang HF, Nahas GG and Hembree WC 3rd: Effects of marihuana inhalation on spermatogenesis of the rat. Adv Biosci1978; 22-23: 419. [PubMed] [Google Scholar]

10. Banerjee A, Singh A, Srivastava Pet al.: Effects of chronic bhang (cannabis) administration on the reproductive system of male mice. Birth Defects Res B Dev Reprod Toxicol2011; 92: 195. [PubMed] [Google Scholar]

11. Dixit VP, Gupta CL and Agrawal M: Testicular degeneration and necrosis induced by chronic administration of cannabis extract in dogs. Endokrinologie1977; 69: 299. [PubMed] [Google Scholar]

12. Kolodny RC, Masters WH, Kolodner RMet al.: Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl J Med1974; 290: 872. [PubMed] [Google Scholar]

13. Gundersen TD, Jorgensen N, Andersson AMet al.: Association between use of marijuana and male reproductive hormones and sem*n quality: a study among 1,215 healthy young men. Am J Epidemiol2015; 182: 473. [PubMed] [Google Scholar]

14. Hembree WC 3rd, Nahas GG, Zeidenberg Pet al.: Changes in human spermatozoa associated with high dose marihuana smoking. Adv Biosci1978; 22-23: 429. [PubMed] [Google Scholar]

15. Zimmerman AM, Zimmerman S and Raj AY: Effects of cannabinoids on spermatogenesis in mice. Adv Biosci1978; 22-23: 407. [PubMed] [Google Scholar]

16. Pacey AA, Povey AC, Clyma JAet al.: Modifiable and non-modifiable risk factors for poor sperm morphology. Hum Reprod2014; 29: 1629. [PubMed] [Google Scholar]

17. Generoso WM, Cain KT, Cornett CVet al.: Tests for induction of dominant-lethal mutations and heritable translocations with tetrahydrocannabinol in male mice. Mutat Res1985; 143: 51. [PubMed] [Google Scholar]

18. Berryman SH, Anderson RA Jr, Weis Jet al.: Evaluation of the co-mutagenicity of ethanol and delta 9-tetrahydrocannabinol with Trenimon. Mutat Res1992; 278: 47. [PubMed] [Google Scholar]

19. Whan LB, West MC, McClure Net al.: Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro. Fertil Steril2006; 85: 653. [PubMed] [Google Scholar]

20. Barbonetti A, Vassallo MR, Fortunato Det al.: Energetic metabolism and human sperm motility: impact of CB₁ receptor activation. Endocrinology2010; 151: 5882. [PMC free article] [PubMed] [Google Scholar]

21. Badawy ZS, Chohan KR, Whyte DAet al.: Cannabinoids inhibit the respiration of human sperm. Fertil Steril2009; 91: 2471. [PubMed] [Google Scholar]

22. Rossato M, Ion Popa F, Ferigo Met al.: Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab2005; 90: 984. [PubMed] [Google Scholar]

23. Cobellis G, Cacciola G, Scarpa Det al.: Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Biol Reprod2006; 75: 82. [PubMed] [Google Scholar]

24. Schuel H and Burkman LJ: A tale of two cells: endocannabinoid-signaling regulates functions of neurons and sperm. Biol Reprod2005; 73: 1078. [PubMed] [Google Scholar]

25. Schuel H, Burkman LJ, Lippes Jet al.: Evidence that anandamide-signaling regulates human sperm functions required for fertilization. Mol Reprod Dev2002; 63: 376. [PubMed] [Google Scholar]

26. Maccarrone M, Barboni B, Paradisi Aet al.: Characterization of the endocannabinoid system in boar spermatozoa and implications for sperm capacitation and acrosome reaction. J Cell Sci2005; 118: 4393. [PubMed] [Google Scholar]

27. Cone EJ, Johnson RE, Moore JDet al.: Acute effects of smoking marijuana on hormones, subjective effects and performance in male human subjects. Pharmacol Biochem Behav1986; 24: 1749. [PubMed] [Google Scholar]

28. Wenger T, Rettori V, Snyder GDet al.: Effects of delta-9-tetrahydrocannabinol on the hypothalamicpituitary control of luteinizing hormone and follicle-stimulating hormone secretion in adult male rats. Neuroendocrinology1987; 46: 488. [PubMed] [Google Scholar]

29. Vescovi PP, Pedrazzoni M, Michelini Met al.: Chronic effects of marihuana smoking on luteinizing hormone, follicle-stimulating hormone and prolactin levels in human males. Drug Alcohol Depend1992; 30: 59. [PubMed] [Google Scholar]

30. Martín-Calderón JL, Muñoz RM, Villanúa MAet al.: Characterization of the acute endocrine actions of (−)-11-hydroxy-delta8-tetrahydrocannabinol-dimethylheptyl (HU-210), a potent synthetic cannabinoid in rats. Eur J Pharmacol1998; 344: 77. [PubMed] [Google Scholar]

31. Wenger T, Fernández-Ruiz JJ and Ramos JA: Immunocytochemical demonstration of CB1 cannabinoid receptors in the anterior lobe of the pituitary gland. J Neuroendocrinol1999; 11: 873. [PubMed] [Google Scholar]

32. Wenger T, Ledent C, Csernus Vet al.: The central cannabinoid receptor inactivation suppresses endocrine reproductive functions. Biochem Biophys Res Commun2001; 284: 363. [PubMed] [Google Scholar]

33. List A, Nazar B, Nyquist Set al.: The effects of delta9-tetrahydrocannabinol and cannabidiol on the metabolism of gonadal steroids in the rat. Drug Metab Dispos1977; 5: 268. [PubMed] [Google Scholar]

34. Mendelson JH, Kuehnle J, Ellingboe Jet al.: Plasma testosterone levels before, during and after chronic marihuana smoking. N Engl J Med1974; 291: 1051. [PubMed] [Google Scholar]

35. Friedrich G, Nepita W and Andre T: Serum testosterone concentrations in cannabis and opiate users. Beitr Gerichtl Med1990; 48: 57. [PubMed] [Google Scholar]

36. Thistle JE, Graubard BI, Braunlin Met al.: Marijuana use and serum testosterone concentrations among U.S. males. Andrology2017; 5: 732. [PMC free article] [PubMed] [Google Scholar]

37. Dixit VP, Sharma VN and Lohiya NK: The effect of chronically administered cannabis extract on the testicular function of mice. Eur J Pharmacol1974; 26: 111. [PubMed] [Google Scholar]

38. Harclerode J: Endocrine effects of marijuana in the male: preclinical studies. NIDA Res Monogr1984; 44: 46. [PubMed] [Google Scholar]

39. Fujimoto GI, Morrill GA, O’Connell MEet al.: Effects of cannabinoids given orally and reduced appetite on the male rat reproductive system. Pharmacology1982; 24: 303. [PubMed] [Google Scholar]

40. Mandal TK and Das NS: Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of antioxidant enzyme systems. Toxicol Ind Health2010; 26: 11. [PubMed] [Google Scholar]

41. Alagbonsi IA, Olayaki LA and 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 Pharmacol2016; 27: 277. [PubMed] [Google Scholar]

42. Chopra GS and Jandu BS: Psychoclinical effects of long-term marijuana use in 275 Indian chronic users. A comparative assessment of effects in Indian and USA users. Ann N Y Acad Sci1976; 282: 95. [PubMed] [Google Scholar]

43. Kolodny RC, Masters WH and Johnson VE: Textbook of Sexual Medicine. Boston: Little Brown & Co; 1979. [Google Scholar]

44. Androvicova R, Horacek J, Tintera Jet al.: Individual prolactin reactivity modulates response of nucleus accumbens to erotic stimuli during acute cannabis intoxication: an fMRI pilot study. Psychopharmacology (Berl)2017; 234: 1933. [PubMed] [Google Scholar]

45. Murphy LL, Gher J, Steger RWet al.: Effects of delta 9-tetrahydrocannabinol on copulatory behavior and neuroendocrine responses of male rats to female conspecifics. Pharmacol Biochem Behav1994; 48: 1011. [PubMed] [Google Scholar]

46. Dhawan K and Sharma A: Restoration of chronic-Delta 9-THC-induced decline in sexuality in male rats by a novel benzoflavone moiety from Passiflora incarnata Linn. Br J Pharmacol2003; 138: 117. [PMC free article] [PubMed] [Google Scholar]

47. Aversa A, Rossi F, Francomano Det al.: Early endothelial dysfunction as a marker of vasculogenic erectile dysfunction in young habitual cannabis users. Int J Impot Res2008; 20: 566. [PubMed] [Google Scholar]

48. Succu S, Mascia MS, Sanna Fet al.: The cannabinoid CB1 receptor antagonist SR 141716A induces penile erection by increasing extra-cellular glutamic acid in the paraventricular nucleus of male rats. Behav Brain Res2006; 169: 274. [PubMed] [Google Scholar]

49. Melis MR, Succu S, Mascia MSet al.: The cannabinoid receptor antagonist SR-141716A induces penile erection in male rats: involvement of paraventricular glutamic acid and nitric oxide. Neuropharmacology2006; 50: 219. [PubMed] [Google Scholar]

50. Center for Behavioral Health Statistics and Quality: 2016 National Survey on Drug Use and Health: Detailed Tables. Rockville, Maryland: Substance Abuse and Mental Health Services Administration; 2017. [Google Scholar]