Researchers discovered the endocannabinoid anandamide in human reproductive fluids and found that both anandamide analogues and THC altered sperm capacitation and fertilizing potential, suggesting cannabis use could affect fertility.
Read this if you use cannabis and are concerned about its effects on fertility.
Sperm fertilizing capacity cut 50% at just 1 nM cannabinoid concentration
What the researchers found
Anandamide, an endocannabinoid, was detected in human seminal plasma, mid-cycle oviductal fluid, and follicular fluid. Human sperm expressed cannabinoid receptors with specific, saturable binding. A metabolically stable anandamide analogue produced dose-dependent effects on sperm: at higher concentrations (2.5 nM) it inhibited hyperactivated motility, while at lower concentrations (0.25 nM) it stimulated it.
Both the anandamide analogue and THC inhibited acrosomal changes needed for fertilization at remarkably low concentrations. Sperm fertilizing capacity in the Hemizona Assay was reduced 50% by just 1 nM of the anandamide analogue. These findings suggested that the endocannabinoid system plays a natural regulatory role in fertility, and that cannabis use could disrupt this regulation.
Why it matters
This study provided the first evidence that the endocannabinoid system was present and active in human reproductive fluids and sperm. The finding that very low concentrations of cannabinoids could significantly impair sperm fertilizing capacity raised important questions about cannabis use and male fertility.
The numbers in context
Cannabinoid receptor binding: KD 9.71 nM on sperm. Anandamide analogue: inhibited hyperactivated motility at 2.5 nM, stimulated at 0.25 nM. Acrosomal changes inhibited at IC50 of 5.9 pM (analogue) and 3.5 nM (THC). Fertilizing capacity reduced 50% at 1 nM.
How the study worked
This was a laboratory study using human reproductive fluids analyzed by HPLC/mass spectrometry to detect anandamide. Cannabinoid receptor binding on human sperm was characterized using radioligand binding assays. Functional effects of cannabinoid agonists and THC on sperm capacitation, hyperactivated motility, acrosomal changes, and fertilizing potential were assessed in vitro.
What this study cannot tell us
All functional experiments were conducted in vitro and may not directly reflect conditions in the reproductive tract. The concentrations of anandamide in reproductive fluids and the concentrations of THC that would reach sperm after cannabis use may differ from those tested. The study did not assess female fertility parameters.
How to read the evidence
This is an in vitro laboratory study providing preliminary evidence of a mechanism that requires in vivo confirmation.
When this study was published
Published in 2002. Subsequent research has confirmed endocannabinoid involvement in reproductive function.
The bigger picture
This study opened a new field of research into endocannabinoid regulation of fertility. Subsequent studies have confirmed endocannabinoid involvement in implantation, placentation, and early pregnancy. The implications for cannabis users trying to conceive have become more clinically relevant as cannabis use has increased.
Questions still open
- Do THC concentrations in the reproductive tract of cannabis users reach levels sufficient to affect sperm function? Does chronic cannabis use alter endocannabinoid levels in reproductive fluids? How does the endocannabinoid system interact with other hormonal regulators of fertility?
Common questions
Can cannabis affect male fertility?
What does the body's endocannabinoid system do in reproduction?
Read the original research
Evidence that anandamide-signaling regulates human sperm functions required for fertilization.
Molecular reproduction and development, 63(3), 376-87
Citation
Schuel, Herbert; Burkman, Lani J; Lippes, Jack; Crickard, Kent; Mahony, Mary C; Giuffrida, Andrea; Picone, Robert P; Makriyannis, Alexandros. (2002). Evidence that anandamide-signaling regulates human sperm functions required for fertilization.. Molecular reproduction and development, 63(3), 376-87.
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