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Pot as a depilatory: CB1 agonists induce catagen in hair follicles
Pot as a depilatory: CB1 agonists induce catagen in hair follicles
Anandamide and THC are both CB1 ligands. This indicates, as the
abstract itself states, that long-term exposure to CB1 ligands may cause
hair to fall out whereas CB1 antagonists (e.g., Rimonabant) may preserve
hair growth.
Ičve indicated in the past that inflammatory intestinal disorders can
involve underexpression of mu opioid and cannabinoid receptors [PMID
17159985]. As low-dose naltrexone can help fight mu opioid
downregulation - and hence LDN has demonstrable efficacy with Crohn's
and IBD - I've suggested dual low-dose cannabinoid antagonists might
also be effective. At a low enough dose, cannabinoid antagonists might
trigger upregulation of the CB receptors instead of blocking them. This
paper indicates if a low-dose CB1 antagonist does upregulate the CB1
receptor then hair loss may be a side effect.
Note that CB1 regulates an awful lot. Blocking it, for instance, could
induce HPA axis dysfunction and circadian problems (which is interesting
since each individual hair follicle recapitulates the entire HPA axis).
The most promising application of this new knowledge is probably in a
topical, though, which would tend to limit collateral damage.
FASEB J. 2007 Jun 12; [Epub ahead of print]
Inhibition of human hair follicle growth by endo- and exocannabinoids.
Telek A, Biro T, Bodo E, Toth BI, Borbiro I, Kunos G,
Paus R.
*Department of Physiology andCell Physiology Research Group of the
Hungarian Academy of Sciences, University of Debrecen, Medical and
Health Science Center, Research Center for Molecular Medicine, Debrecen,
Hungary;Department of Dermatology, University Hospital
Schleswig-Holstein, Campus Lubeck, University of Lubeck, Lubeck,
Germany; andNational Institute on Alcohol Abuse and Alcoholism, National
Institutes of Health, Bethesda, Maryland, USA.
Recent studies strongly suggest that the cannabinoid system is a key
player in cell growth control. Since the organ-culture of human hair
follicles (HF) offers an excellent, clinically relevant model for
complex tissue interaction systems, we have asked whether the
cannabinoid system plays a role in hair growth control. Here, we show
that human scalp HF, intriguingly, are both targets and sources of
endocannabinoids. Namely, the endocannabinoid N-arachidonoylethanolamide
(anandamide, AEA) as well as the exocannabinnoid Delta
(9)-tetrahydrocannabinol dose-dependently inhibited hair shaft
elongation and the proliferation of hair matrix keratinocytes, and
induced intraepithelial apoptosis and premature HF regression (catagen).
These effects were inhibited by a selective antagonist of cannabinoid
receptor-1 (CB1). In contrast to CB2, CB1 was expressed in a hair
cycle-dependent manner in the human HF epithelium. Since we successfully
identified the presence of endocannabinoids in human HF, our data
strongly suggest that human HF exploit a CB1-mediated endocannabinoid
signaling system for negatively regulating their own growth. Clinically,
CB1 agonists may therefore help to manage unwanted hair growth, while
CB1 antagonists might counteract hair loss. Finally, human HF organ
culture offers an instructive, physiologically relevant new research
tool for dissecting "nonclassical" effects of endocannabinoids and their
receptor-mediated signaling in general.--Telek, A., Biro, T., Bodo, E.,
Toth, B. I., Borbiro, I., Kunos, G., Paus, R. Inhibition of human hair
follicle growth by endo- and exocannabinoids.
PMID: 17567570 [PubMed - as supplied by publisher]
Related Links
A hot new twist to hair biology: involvement of vanilloid receptor-1
(VR1/TRPV1) signaling in human hair growth control. [Am J Pathol. 2005]
PMID: 15793280
Towards dissecting the pathogenesis of retinoid-induced hair loss:
all-trans retinoic acid induces premature hair follicle regression
(catagen) by upregulation of transforming growth factor-beta2 in the
dermal papilla. [J Invest Dermatol. 2005] PMID: 15955085
Interferon-gamma is a potent inducer of catagen-like changes in
cultured human anagen hair follicles. [Br J Dermatol. 2005]
PMID: 15840090
Epithelial growth control by neurotrophins: leads and lessons from
the hair follicle. [Prog Brain Res. 2004] PMID: 14699982
Human scalp hair follicles are both a target and a source of
prolactin, which serves as an autocrine and/or paracrine promoter of
apoptosis-driven hair follicle regression. [Am J Pathol. 2006]
PMID: 16507890
Notes:
intranigral capsaicin injections can kill dopamine neurons; activation
both of CB1 and TRPV1 induce cell death; anandamide is a ligand both for
CB1 and TRPV1 and may contribute to neurodegeneration [PMID 15659603];
anandamide, by activating TRPV1, induces bladder hyperreflexia and
nociceptive transmission in cystitis; however, RTX, a super agonist of
TRPV1, desensitizes against this reaction (perhaps by killing VR1
nerves?) as does a TRPV1 antagonist [PMID 15601931];
transcription of the CB1 gene in CD4(+) Jurkat T cells was strongly
induced by Delta(9)-tetrahydrocannabinol (THC), whereas the CB2 gene was
not regulated; induction of CB1 gene expression is mediated by CB2
receptors only, as demonstrated by using the CB1 and CB2 agonists
R(+)-methanandamide and JWH 015, respectively, and combinations of THC
plus CB1- and CB2-specific antagonists; after activation of CB2
receptors, the transcription factor STAT5 is phosphorylated; STAT5 then
transactivates IL-4; IL-4 mRNA induction as well as IL-4 protein release
is necessary for the following induction of the CB1 gene;
transactivation of the CB1 gene in response to IL-4 is then mediated by
the transcription factor STAT6; an increase in CB1-mediated
phosphorylation of MAPK in cells prestimulated with CB2-specific
agonists suggests up-regulation of functional CB1 receptor proteins
[PMID 17041005]
Anandamide and THC are both CB1 ligands. This indicates, as the
abstract itself states, that long-term exposure to CB1 ligands may cause
hair to fall out whereas CB1 antagonists (e.g., Rimonabant) may preserve
hair growth.
Ičve indicated in the past that inflammatory intestinal disorders can
involve underexpression of mu opioid and cannabinoid receptors [PMID
17159985]. As low-dose naltrexone can help fight mu opioid
downregulation - and hence LDN has demonstrable efficacy with Crohn's
and IBD - I've suggested dual low-dose cannabinoid antagonists might
also be effective. At a low enough dose, cannabinoid antagonists might
trigger upregulation of the CB receptors instead of blocking them. This
paper indicates if a low-dose CB1 antagonist does upregulate the CB1
receptor then hair loss may be a side effect.
Note that CB1 regulates an awful lot. Blocking it, for instance, could
induce HPA axis dysfunction and circadian problems (which is interesting
since each individual hair follicle recapitulates the entire HPA axis).
The most promising application of this new knowledge is probably in a
topical, though, which would tend to limit collateral damage.
FASEB J. 2007 Jun 12; [Epub ahead of print]
Inhibition of human hair follicle growth by endo- and exocannabinoids.
Telek A, Biro T, Bodo E, Toth BI, Borbiro I, Kunos G,
Paus R.
*Department of Physiology andCell Physiology Research Group of the
Hungarian Academy of Sciences, University of Debrecen, Medical and
Health Science Center, Research Center for Molecular Medicine, Debrecen,
Hungary;Department of Dermatology, University Hospital
Schleswig-Holstein, Campus Lubeck, University of Lubeck, Lubeck,
Germany; andNational Institute on Alcohol Abuse and Alcoholism, National
Institutes of Health, Bethesda, Maryland, USA.
Recent studies strongly suggest that the cannabinoid system is a key
player in cell growth control. Since the organ-culture of human hair
follicles (HF) offers an excellent, clinically relevant model for
complex tissue interaction systems, we have asked whether the
cannabinoid system plays a role in hair growth control. Here, we show
that human scalp HF, intriguingly, are both targets and sources of
endocannabinoids. Namely, the endocannabinoid N-arachidonoylethanolamide
(anandamide, AEA) as well as the exocannabinnoid Delta
(9)-tetrahydrocannabinol dose-dependently inhibited hair shaft
elongation and the proliferation of hair matrix keratinocytes, and
induced intraepithelial apoptosis and premature HF regression (catagen).
These effects were inhibited by a selective antagonist of cannabinoid
receptor-1 (CB1). In contrast to CB2, CB1 was expressed in a hair
cycle-dependent manner in the human HF epithelium. Since we successfully
identified the presence of endocannabinoids in human HF, our data
strongly suggest that human HF exploit a CB1-mediated endocannabinoid
signaling system for negatively regulating their own growth. Clinically,
CB1 agonists may therefore help to manage unwanted hair growth, while
CB1 antagonists might counteract hair loss. Finally, human HF organ
culture offers an instructive, physiologically relevant new research
tool for dissecting "nonclassical" effects of endocannabinoids and their
receptor-mediated signaling in general.--Telek, A., Biro, T., Bodo, E.,
Toth, B. I., Borbiro, I., Kunos, G., Paus, R. Inhibition of human hair
follicle growth by endo- and exocannabinoids.
PMID: 17567570 [PubMed - as supplied by publisher]
Related Links
A hot new twist to hair biology: involvement of vanilloid receptor-1
(VR1/TRPV1) signaling in human hair growth control. [Am J Pathol. 2005]
PMID: 15793280
Towards dissecting the pathogenesis of retinoid-induced hair loss:
all-trans retinoic acid induces premature hair follicle regression
(catagen) by upregulation of transforming growth factor-beta2 in the
dermal papilla. [J Invest Dermatol. 2005] PMID: 15955085
Interferon-gamma is a potent inducer of catagen-like changes in
cultured human anagen hair follicles. [Br J Dermatol. 2005]
PMID: 15840090
Epithelial growth control by neurotrophins: leads and lessons from
the hair follicle. [Prog Brain Res. 2004] PMID: 14699982
Human scalp hair follicles are both a target and a source of
prolactin, which serves as an autocrine and/or paracrine promoter of
apoptosis-driven hair follicle regression. [Am J Pathol. 2006]
PMID: 16507890
Notes:
intranigral capsaicin injections can kill dopamine neurons; activation
both of CB1 and TRPV1 induce cell death; anandamide is a ligand both for
CB1 and TRPV1 and may contribute to neurodegeneration [PMID 15659603];
anandamide, by activating TRPV1, induces bladder hyperreflexia and
nociceptive transmission in cystitis; however, RTX, a super agonist of
TRPV1, desensitizes against this reaction (perhaps by killing VR1
nerves?) as does a TRPV1 antagonist [PMID 15601931];
transcription of the CB1 gene in CD4(+) Jurkat T cells was strongly
induced by Delta(9)-tetrahydrocannabinol (THC), whereas the CB2 gene was
not regulated; induction of CB1 gene expression is mediated by CB2
receptors only, as demonstrated by using the CB1 and CB2 agonists
R(+)-methanandamide and JWH 015, respectively, and combinations of THC
plus CB1- and CB2-specific antagonists; after activation of CB2
receptors, the transcription factor STAT5 is phosphorylated; STAT5 then
transactivates IL-4; IL-4 mRNA induction as well as IL-4 protein release
is necessary for the following induction of the CB1 gene;
transactivation of the CB1 gene in response to IL-4 is then mediated by
the transcription factor STAT6; an increase in CB1-mediated
phosphorylation of MAPK in cells prestimulated with CB2-specific
agonists suggests up-regulation of functional CB1 receptor proteins
[PMID 17041005]
