Summary
Background
Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number
of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid
(CB) receptors are present in human skin and anandamide, an endogenous CB receptor
ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammatory
disease also characterised in part by epidermal keratinocyte hyper-proliferation.
Objective
We investigated the plant cannabinoids Δ-9 tetrahydrocannabinol, cannabidiol, cannabinol
and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating
human keratinocyte cell line and for any involvement of cannabinoid receptors.
Methods
A keratinocyte proliferation assay was used to assess the effect of treatment with
cannabinoids. Cell integrity and metabolic competence confirmed using lactate-dehydrogenase
and adenosine tri-phosphate assays. To determine the involvement of the receptors,
specific agonist and antagonist were used in conjunction with some phytocannabinoids.
Western blot and RT-PCR analysis confirmed presence of CB1 and CB2 receptors.
Results
The cannabinoids tested all inhibited keratinocyte proliferation in a concentration-dependent
manner. The selective CB2 receptor agonists JWH015 and BML190 elicited only partial
inhibition, the non-selective CB agonist HU210 produced a concentration-dependent
response, the activity of theses agonists were not blocked by either CB1/CB2 antagonists.
Conclusion
The results indicate that while CB receptors may have a circumstantial role in keratinocyte
proliferation, they do not contribute significantly to this process. Our results show
that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential
role for cannabinoids in the treatment of psoriasis.
Abbreviations:
CBG (cannabigerol), CBD (cannabidiol), THC (tetrahydrocannabinol), CB (cannabinoid)Keywords
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Article info
Publication history
Accepted:
October 31,
2006
Received in revised form:
October 17,
2006
Received:
June 16,
2006
Identification
Copyright
© 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.
