Cannabis and Male Fertility: What the Science Actually Shows

A new narrative review maps the endocannabinoid system’s dual role in male reproductive health, offering therapeutic promise for conditions like erectile dysfunction and prostatitis while raising concerns about chronic THC exposure and its effects on spermatogenesis, hormonal balance, and prostate cancer biology.

Why This Matters

Cannabis use among men of reproductive age is rising sharply as legalization expands worldwide, yet clinicians have limited synthesized evidence to guide conversations about fertility and sexual health risks. The endocannabinoid system is deeply embedded in male reproductive physiology, making it both a promising therapeutic target and a point of vulnerability when exogenous cannabinoids are introduced chronically. This review arrives at a moment when the gap between patient behavior and clinical knowledge is widening, and when both clinicians and patients urgently need a clearer picture of what the science does and does not support.

Clinical Summary

The endocannabinoid system, composed of receptors (CB1, CB2, GPR55, TRPV1, PPARs), endogenous ligands (anandamide and 2-AG), and regulatory enzymes (FAAH, MAGL), is functionally active throughout the male reproductive tract. A 2025 narrative review published in Maturitas by Ferrara and colleagues synthesizes preclinical, mechanistic, and limited clinical literature on how this system modulates spermatogenesis, erectile function, and prostatic inflammation. The mechanistic rationale is biologically specific: CB1 receptors in the corpus cavernosum facilitate smooth muscle relaxation through nitric oxide pathways, while CB2 receptor activation in prostatic tissue reduces pro-inflammatory cytokine production. In the testes, CB1 receptors help regulate the staged progression of spermatogenesis. These pathways suggest that endogenous cannabinoid signaling at physiological concentrations supports male reproductive health, while supraphysiological THC exposure from chronic cannabis use may overwhelm the same regulatory circuits.

The review reports that chronic THC exposure in preclinical models is associated with reduced sperm motility, disrupted hormonal axes including suppressed testosterone, and altered proliferation patterns in prostate cancer cell lines, with both pro-tumor and anti-tumor signals reported depending on context. CB2 receptor agonism shows anti-inflammatory potential relevant to prostatitis and benign prostatic hyperplasia. However, the review’s primary limitations are substantial: most supporting evidence derives from animal or cell-based studies, the search methodology is non-systematic without PRISMA adherence or formal quality appraisal, and the total number of included studies is not reported. The authors correctly conclude that the evidence base is insufficient for definitive clinical guidance and that well-designed human studies, particularly randomized controlled trials and longitudinal cohort investigations, are urgently needed before firm recommendations can be made.

Dr. Caplan’s Take

This review does a useful job of mapping the endocannabinoid system’s involvement in male reproductive physiology, and the mechanistic framework it presents is genuinely interesting. The problem is that patients do not ask me about receptor pharmacology. They ask whether their cannabis use is affecting their fertility or their sexual function, and the honest answer right now is that we do not have enough quality human data to be certain either way. The preclinical signals are concerning enough to warrant a serious conversation, but not strong enough to support definitive claims of harm or safety.

In practice, when a male patient using cannabis presents with fertility concerns, I treat it as a modifiable risk factor worth discussing alongside sleep, stress, metabolic health, and other exposures. I recommend reducing or eliminating high-THC cannabis use during active attempts to conceive, not because we have proof of causation, but because the preclinical evidence leans toward disruption and the cost of temporary cessation is low. I do not use this evidence to make blanket prohibitions, and I am transparent with patients about what we know versus what we suspect.

Clinical Perspective

This narrative review consolidates a dispersed literature into a single reference point, which has practical value for clinicians fielding patient questions about cannabis and reproduction. However, it sits early in the research arc. The mechanistic plausibility is strong, with well-characterized receptor distributions, identified signaling cascades, and consistent preclinical signals. What remains missing is the translational bridge: dose-response data in humans, longitudinal fertility outcomes in cannabis users, and controlled studies separating THC effects from other cannabis constituents. Clinicians should understand that this review confirms biologic plausibility but does not confirm clinical causation. It cannot support statements like “cannabis causes infertility” in patient-facing materials, though it does justify informed, nuanced risk counseling.

From a pharmacological standpoint, clinicians should be aware that THC’s effects on the hypothalamic-pituitary-gonadal axis may interact with hormonal therapies, including testosterone replacement and clomiphene citrate, though no direct interaction studies are cited in this review. The anti-inflammatory potential of CB2 agonism in prostatic tissue is worth tracking but is not yet actionable. The single most concrete step clinicians can take now is to routinely include cannabis use in reproductive health histories for male patients, documenting frequency, product type, and THC concentration, so that future outcome data can be meaningfully interpreted.

Study at a Glance

Study Type

Narrative review

Population

Male reproductive tissues and pathways; preclinical models (cell lines, animal studies) and limited human clinical data

Intervention

Endocannabinoid system modulation (endogenous cannabinoids AEA, 2-AG; exogenous THC)

Comparator

Not applicable (narrative synthesis, no controlled comparison)

Primary Outcomes

Spermatogenesis, hormonal balance, erectile function, prostatitis, prostate cancer cell proliferation

Sample Size

Not reported; number of included studies not specified

Journal

Maturitas

Year

2025 (accepted November 2024)

DOI

10.1016/j.maturitas.2024.108156

Funding Source

Not disclosed

What Kind of Evidence Is This

This is a narrative review, which occupies a relatively low position in the evidence hierarchy compared to systematic reviews or meta-analyses. It employs a described but non-systematic search strategy across PubMed, Scopus, Web of Science, and Google Scholar without PRISMA adherence, registered protocol, or formal risk-of-bias assessment of included studies. The single most important inference constraint is that selection bias in the included literature cannot be excluded, meaning the synthesis may not represent the full scope or balance of available evidence.

How This Fits With the Broader Literature

The review’s findings are broadly consistent with earlier work, including the systematic review by Payne and colleagues (2019) examining cannabis and male fertility, which similarly identified preclinical signals of harm to spermatogenesis without finding conclusive human evidence. The erectile function findings align with Shamloul and Bella’s (2011) review of cannabis and sexual function, which noted paradoxical effects depending on dose and chronicity. What this review adds is a more complete receptor-level map of the endocannabinoid system across the male reproductive tract and a broader scope encompassing prostatic pathology. However, like its predecessors, it ultimately arrives at the same conclusion: the mechanistic groundwork is compelling, but the clinical evidence has not kept pace with either the biology or the epidemiology of cannabis use.

Common Misreadings

The most likely overinterpretation is reading this review as evidence that cannabis use causes male infertility or erectile dysfunction. The review presents mechanistic plausibility and preclinical associations, not demonstrated causal relationships in human populations. Most of the cited evidence on spermatogenesis and hormonal disruption comes from animal models or cell culture systems where cannabinoid concentrations, exposure durations, and biological contexts differ substantially from human recreational use. Similarly, the prostate cancer findings should not be interpreted as evidence that cannabis either causes or prevents prostate cancer; the signals are mixed and the models are preliminary.

Bottom Line

This narrative review establishes that the endocannabinoid system is deeply involved in male reproductive physiology and provides a useful mechanistic framework for understanding how chronic THC exposure might disrupt fertility, hormonal balance, and prostatic health. It does not establish clinical causation in humans. For now, it supports including cannabis in male reproductive health assessments and counseling patients about plausible but unproven risks, while we wait for the controlled human studies that the field urgently needs.

References

1. Ferrara F, et al. The endocannabinoid system and its potential role in male reproductive health. Maturitas. 2025;193:108156. doi:10.1016/j.maturitas.2024.108156
2. Payne KS, Mazur DJ, Hotaling JM, Pastuszak AW. Cannabis and male fertility: a systematic review. J Urol. 2019;202(4):674-681. doi:10.1097/JU.0000000000000248
3. Shamloul R, Bella AJ. Impact of cannabis use on male sexual health. J Sex Med. 2011;8(4):971-975. doi:10.1111/j.1743-6109.2010.02198.x