The holidays are hectic and challenging enough. They can at times, be both emotionally, and financially stressful. Significantly increased shedding, as if to add insult to injury, is not uncommon. It has long been posited by the medical establishment that pattern hair loss is exclusively genetic and is unaffected by stress. There is now published evidence to the contrary that elucidates the specific mechanisms involved.

      These articles identify a specific pathways by stress can cause hairloss, and specific pathways for simple and successful intervention and/or prophylaxis.

Stress, Neurogenic Inflammation and Hair Loss
Andrea Marliani, Paolo Gigli e Daniele Campo

For many years, perhaps for even several decades, stress has been indicated as a possible cause of hair loss though, to tell the truth, there is no real proof of this. Some patients under stress show widespread hair loss, which is more noticeable in the central area just in front of the crown, while hair growth continues along the front hairline. Marino Salin calls this “incidenza nervosa”.

This fact is well known to all those who are actively involved in hair care. But how it happens is not clear to anyone.

Biological response to stress usually takes place by way of the hypothalamus-hypophysis-surrenal gland axis. There is however another mode, involving a large number of interrelated peripheral neurotransmitters and hormones which are released by the non-myelinic nerve fibres of the skin and have a direct effect on the way an organism reacts to stress.

Psychological or physical stress sets off a chain of molecular reactions. It does this by way of the Nerve Growth Factor, the Substance P and Catecholamins. These are all key players which limit hair growth. Let us see.

Each hair follicle has a rich nervous plexus. It’s important and interesting to know that this follicular nervous plexus is directly connected with the cerebral cortex. The follicular nervous plexus is partly composed of motor fibres but it is mainly composed of sensory fibres and also of sympathetic non-myelinic noradrenergic free ended fibres.

Stimulated by Nerve Growth Factor, which increases under stress, the sensory fibres are able to liberate Substance P. Substance P is considered the main pain signal transmitter from the periphery to the nerve centres. Substance P attracts inflammation mediators. Substance P causes macrophage and mast cell degranulation with production of inflammatory cytokines from lymphocytes leading to induction and inhibition of the keratinocyte proliferation in the follicle and in the hair matrix and a videomicroscope will show a clear depressed erythematous ring around the infundibula. We are talking about neurogenic inflammation. Daniele Campo calls it “Psychogenetic Alopecia”. For patients, who have no family history of Androgenetic Alopecia and show widespread hair loss which is more noticeable in the central area, just in the front of the crown, while hair growth continues along the front hairline, we need to consider a diagnosis of “Psychogenetic Alopecia”.

Let us now consider the perifollicular sympathetic plexus. The sympathetic plexus is able to release noradrenaline into the intercellular perifollicular spaces and noradrenaline is a powerful vasoconstrictor and inhibitor of the adenil cyclase enzyme. If the adenil cyclase enzyme is inhibited or completely blocked the entire kinase system chain is slowed down and glycolysis, the pentose phosphate shunt and the Krebs cycle are also slowed down, if not completely blocked. If glycolysis stops, the hair’s energetic metabolism is blocked and so are the mitoses of the hair matrix. The interruption of glucose metabolism turns off the supply of energy and ends the anagen phase. As we saw earlier, the sympathetic plexus is able to release noradrenaline into the intercellular and perifollicular spaces, The visible, and well-known, effect is horripilation.

But if there is excess adrenergic tone in the metabolic system, then there is also vasoconstriction, ischemia and hypoxia and if there is hypoxia, glycolysis leads to lactic acid.

The system’s pH is lowered, and the Krebs cycle (which has an ideal pH of 7.35) becomes slow and incapable of disposing of pyruvic and lactic acids and, as in a hypoxic and tired muscle, there is an increase in lactic acid. In these conditions, using a microscope in polarized light, a large number of hairs which have been removed for trichogram examination, will have a strange image. There is damage to the anchoring system of the inner sheath. According to Marino Salin it is lactic acid that causes caustic damage to the inner sheath and this sheath seems to be raised above the hair cuticle. Lactic acid leads to degradation of the inner sheath because of the caustic effect. Hair loss, in the form of Telogen Effluvium, is the result.

Capsures inhibits Neurogenic inflammation to avoid Psychogenetic Alopecia.

Comment: Capsures is an oral combination of trans Resveratrol and a 95% Extract of Curcumin, and has been on the market in Europe for approximately 2 and a half years. As mentioned in prior updates, one can put this combo together at a much more bio-available and higher millgram dosage at a fraction of the cost. The feedback for both Capsures and the Resveratrol/Super Bio-Curcumin combo for both stress related and androgenetic hair loss has been uniformly positive.

      Here are some other studies that directly implicate Substance P mediating effects on neurogenic inflammation and the Endocannabinoid (ECS) system in the regulation of hair growth. In essence, stress increases the release of Substance P, and disrupts the delicate ECS balance, resulting in stress related hair loss.

Am J Pathol. 2007 Dec;171(6):1872-86. Epub 2007 Nov 30.

Probing the effects of stress mediators on the human hair follicle: substance P holds central position.

Peters EM, Liotiri S, Bodó E, Hagen E, Bíró T, Arck PC, Paus R.

Department of Dermatology, University Hospital Schleswig-Holstein, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.

Stress alters murine hair growth, depending on substance P-mediated neurogenic inflammation and nerve growth factor (NGF), a key modulator of hair growth termination (catagen induction). Whether this is of any relevance in human hair follicles (HFs) is completely unclear. Therefore, we have investigated the effects of substance P, the central cutaneous prototypic stress-associated neuropeptide, on normal, growing human scalp HFs in organ culture. We show that these prominently expressed substance P receptor (NK1) at the gene and protein level. Organ-cultured HFs responded to substance P by premature catagen development, down-regulation of NK1, and up-regulation of neutral endopeptidase (degrades substance P). This was accompanied by mast cell degranulation in the HF connective tissue sheath, indicating neurogenic inflammation. Substance P down-regulated immunoreactivity for the growth-promoting NGF receptor (TrkA), whereas it up-regulated NGF and its apoptosis- and catagen-promoting receptor (p75NTR). In addition, MHC class I and beta2-microglobulin immunoreactivity were up-regulated and detected ectopically, indicating collapse of the HF immune privilege. In conclusion, we present a simplistic, but instructive, organ culture assay to demonstrate sensitivity of the human HF to key skin stress mediators. The data obtained therewith allow one to sketch the first evidence-based biological explanation for how stress may trigger or aggravate telogen effluvium and alopecia areata.

The dietary polyphenols trans-resveratrol and curcumin selectively bind human CB1 cannabinoid receptors with nanomolar affinities and function as antagonists/inverse agonists


The dietary polyphenols trans-resveratrol (found in red wine) and curcumin (found in curry powders) exert anti-inflammatory and anti-oxidant effects via poorly defined mechanisms. Interestingly, cannabinoids, derived from the marijuana plant (Cannabis sativa), produce similar protective effects via CB1 and CB2 receptors. We examined whether trans-resveratrol, curcumin and ASC-J9 (a curcumin analog) act as ligands at cannabinoid receptors. All three bind to hCB1 and mCB1 receptors with nanomolar affinities, displaying only micromolar affinities for hCB2 receptors. Characteristic of inverse agonists, the polyphenols inhibit basal G-protein activity in membranes prepared from CHO-hCB1 cells or mouse brain, that is reversed by a neutral CB1 antagonist. Furthermore, they competitively antagonize G-protein activation produced by a CB1 agonist. In intact CHO-hCB1 cells, the polyphenols act as neutral antagonists, producing no effect when tested alone, while competitively antagonizing CB1 agonist mediated inhibition of adenylyl cyclase activity. Confirming their neutral antagonist profile in cells, the polyphenols similarly attenuate stimulation of adenylyl cyclase activity produced by a CB1 inverse agonist. In mice, the polyphenols dose-dependently reverse acute hypothermia produced by a CB1 agonist. Upon repeated administration, the polyphenols also reduce body weight in mice similar to that produced by a CB1 antagonist/inverse agonist. Finally, trans-resveratrol and curcumin share common structural motifs with other known cannabinoid receptor ligands. Collectively, we suggest that trans-resveratrol and curcumin act as antagonists/inverse agonists at CB1 receptors at dietary relevant concentrations. Therefore, these polyphenols and their derivatives might be developed as novel, non-toxic CB1 therapeutics for obesity and/or drug dependence.

The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities

      Tamás Bíró, Balázs I. Tóth, György Haskó, Ralf Paus, and Pál Pacher

      The newly discovered endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids present in virtually all tissues, their G-protein-coupled cannabinoid receptors, biosynthetic pathways and metabolizing enzymes) has been implicated in multiple regulatory functions both in health and disease. Recent studies have intriguingly suggested the existence of a functional ECS in the skin and implicated it in various biological processes (e.g. proliferation, growth, differentiation, apoptosis and cytokine, mediator or hormone production of various cell types of the skin and appendages, such as the hair follicle and sebaceous gland). It seems that the main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced prolifer0ation, differentiation and survival, as well as immune competence and/or tolerance, of skin cells. The disruption of this delicate balance might facilitate the development of multiple pathological conditions and diseases of the skin (e.g. acne, seborrhea, allergic dermatitis, itch and pain, psoriasis,hair growth disorders, systemic sclerosis and cancer).

      It has been established that the combination of Resveratrol and Curcumin grows hair in those with Androgenetic Alopecia. It has also been shown that both Resveratrol/SuperBio- Curcumin and Capsaicin act as Cannabinoid receptor 1 antagonists, (in addition to its down-regulating effects on Substance P), explaining its use as an effective intervention for both stress and hormone related hair loss.