Long-term use of HU210 adversely affects spermatogenesis in rats by modulating the endocannabinoid system

S. E.M. Lewis*, R. Paro, L. Borriello, L. Simon, L. Robinson, Z. Dincer, G. Riedel, N. Battista, M. Maccarrone

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


Recent societal acceptance of cannabinoids as recreational and therapeutic drugs has posed a potential hazard to male reproductive health. Mammals have a highly sophisticated endogenous cannabinoid (ECS) system that regulates male (and female) reproduction and exo-cannabinoids may influence it adversely. Therefore it is imperative to determine their effects on male reproduction so that men can make informed choices as to their use. Here, an animal model was used to administer HU210, a synthetic analogue of Δ9-tetrahydrocannabinol (THC) and potent cannabinoid receptor (CB) agonist to determine its effects on reproductive organ weights, spermatogenesis, testicular histology and sperm motility. Its effects on the physiological endocannabinoid system were also investigated. Spermatogenesis was markedly impaired with reductions in total sperm count after 2weeks of exposure. Spermatogenic efficiency was depleted, and Sertoli cell number decreased as exposure time increased with seminiferous tubules showing germ cell depletion developing into atrophy in some cases. Sperm motility was also adversely affected with marked reductions from 2weeks on. HU210 also acted on the sperm's endocannabinoid system. Long-term use of exo-cannabinoids has adverse effects on both spermatogenesis and sperm function. These findings highlight the urgent need for studies evaluating the fertility potential of male recreational drug users. HU210, a selective agonist for CB1 and CB2 cannabinoid receptors impairs spermatogenesis and sperm motility and deregulates the endocannabinoid system.

Original languageEnglish
Pages (from-to)731-740
Number of pages10
JournalInternational journal of andrology
Issue number5
Early online date21 Mar 2012
Publication statusPublished - Oct 2012

Bibliographical note

We are grateful to the staff of the animal facility at University of Aberdeen for their support and also Dr Louise Atkinson for her help with the manuscript preparation. Financial support: Ulster Garden Villages, Organon Schering – Plough.


  • Atrophy
  • DNA
  • Endocannabinoid
  • Sertoli cell
  • Sperm
  • Spermatogenesis
  • Testis


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