Category Archives: Acne

Cannabinoid system in the skin – a possible target for future therapies in dermatology.

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“Cannabinoids and their derivatives are group of more than 60 biologically active chemical agents, which have been used in natural medicine for centuries.

The major agent of exogenous cannabinoids is Delta(9)-tetrahydrocannabinol (Delta(9)-THC), natural psychoactive ingredient of marijuana.

Recent discoveries of endogenous cannabinoids (e.g. arachidonoylethanolamide, 2-arachidonoylglycerol or palmithyloethanolamide) and their receptors initiated discussion on the role of cannabinoid system in physiological conditions as well as in various diseases.

Based on the current knowledge, it could be stated that cannabinoids are important mediators in the skin, however their role have not been well elucidated yet.

In our review, we summarized the current knowledge about the significant role of the cannabinoid system in the cutaneous physiology and pathology, pointing out possible future therapeutic targets.”

http://www.ncbi.nlm.nih.gov/pubmed/19664006

Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrheic skin and acne treatment.

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“Acne is a common skin disease characterized by elevated sebum production and inflammation of the sebaceous glands.

We have previously shown that a non-psychotropic phytocannabinoid ((-)-cannabidiol [CBD]) exerted complex anti-acne effects by normalizing “pro-acne agents”-induced excessive sebaceous lipid production, reducing proliferation and alleviating inflammation in human SZ95 sebocytes.

Therefore, in the current study we aimed to explore the putative anti-acne effects of further non-psychotropic phytocannabinoids ((-)-cannabichromene [CBC], (-)-cannabidivarin [CBDV], (-)-cannabigerol [CBG], (-)-cannabigerovarin [CBGV] and (-)-Δ9 -tetrahydrocannabivarin [THCV]).

Viability and proliferation of human SZ95 sebocytes were investigated by MTT- and CyQUANT-assays; cell death and lipid synthesis were monitored by DilC1 (5)-SYTOX Green labelling and Nile Red staining, respectively. Inflammatory responses were investigated by monitoring expressions of selected cytokines upon lipopolysaccharide treatment (RT-qPCR, ELISA). Up to 10 μM, the phytocannabinoids only negligibly altered viability of the sebocytes, whereas high doses (≥50 μM) induced apoptosis.

Interestingly, basal sebaceous lipid synthesis was differentially modulated by the substances: CBC and THCV suppressed it, CBDV had only minor effects, whereas CBG and CBGV increased it.

Importantly, CBC, CBDV and THCV significantly reduced arachidonic acid (AA)-induced “acne-like” lipogenesis.

Moreover, THCV suppressed proliferation, and all phytocannabinoids exerted remarkable anti-inflammatory actions.

Our data suggest that CBG and CBGV may have potential in the treatment of dry-skin syndrome, whereas CBC, CBDV and especially THCV show promise to become highly efficient, novel anti-acne agents.

Moreover, based on their remarkable anti-inflammatory actions, phytocannabinoids could be efficient, yet safe novel tools in the management of cutaneous inflammations.”

http://www.ncbi.nlm.nih.gov/pubmed/27094344

http://www.thctotalhealthcare.com/category/acne/

ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target.

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“Cannabis sativa is also popularly known as marijuana. It is being cultivated and used by man for recreational and medicinal purposes from many centuries.

Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries.

The research of drugs acting on endocannabinoid system has seen many ups and down in recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve “protective role” in many medical conditions.

Several diseases like emesis, pain, inflammation, multiple sclerosis, anorexia, epilepsy, glaucoma, schizophrenia, cardiovascular disorders, cancer, obesity, metabolic syndrome related diseases, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease and Tourette’s syndrome could possibly be treated by drugs modulating endocannabinoid system.

Presently, cannabinoid receptor agonists like nabilone and dronabinol are used for reducing the chemotherapy induced vomiting. Sativex (cannabidiol and THC combination) is approved in the UK, Spain and New Zealand to treat spasticity due to multiple sclerosis. In US it is under investigation for cancer pain, another drug Epidiolex (cannabidiol) is also under investigation in US for childhood seizures. Rimonabant, CB1 receptor antagonist appeared as a promising anti-obesity drug during clinical trials but it also exhibited remarkable psychiatric side effect profile. Due to which the US Food and Drug Administration did not approve Rimonabant in US. It sale was also suspended across the EU in 2008.

Recent discontinuation of clinical trial related to FAAH inhibitor due to occurrence of serious adverse events in the participating subjects could be discouraging for the research fraternity. Despite of some mishaps in clinical trials related to drugs acting on endocannabinoid system, still lot of research is being carried out to explore and establish the therapeutic targets for both cannabinoid receptor agonists and antagonists.

One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that acts selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted.

Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids.

In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as “protective” and “disease inducing substance”, time-dependent changes in the expression of cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27086601

The safety and efficacy of 3% Cannabis seeds extract cream for reduction of human cheek skin sebum and erythema content.

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“Escalated sebum fabrication is seen with an unattractive look and adds to the growth of acne. We aimed to investigate the efficacy and safety of 3%Cannabis seeds extract cream on human cheek skin sebum and erythema content.

For this purpose, base plus 3% Cannabis seeds extract and base (control) were prepared for single blinded and comparative study. Healthy males were instructed to apply the base plus 3% Cannabis seeds extract and base twice a day to their cheeks for 12 weeks.

Adverse events were observed to determine skin irritation. Measurements for sebum and erythema content were recorded at baseline, 2nd, 4th, 6th, 8th, 10th and 12th week in a control room with Sebumeter and Mexameter.

Base plus 3% Cannabis seeds extract was found to be safe in volunteers.

Measurements demonstrated that skin sebum and erythema content of base plus 3%Cannabis seeds extract treated side showed significant decrease (p<0.05) compared with base treated side.

Base plus 3% Cannabis seeds extract showed safety.

It was well tolerated for the reduction of skin sebum and erythema content.

Its improved efficacy could be suggested for treatment of acne vulgaris, seborrhea, papules and pustules to get attractive facial appearance.”

Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling.

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Figure 1.

“To further investigate the role of the cannabinoid system in pilosebaceous unit biology, we have explored in the current study whether and how endocannabinoids have an impact on human sebaceous gland biology…

Here, we provide the first evidence that SZ95 sebocytes express CB2 but not CB1…

…our results collectively suggest that human sebocytes utilize a paracrine-autocrine, endogenously active, CB2-mediated endocannabinoid signaling system for positively regulating lipid production and cell death.

CB2 antagonists or agonists therefore deserve to be explored in the management of skin disorders characterized by sebaceous gland dysfunctions (e.g., acne vulgaris, seborrhea, dry skin).”

http://www.fasebj.org/content/22/10/3685.long

Endocannabinoid signaling and epidermal differentiation.

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“Endocannabinoids represent a class of endogenous lipid mediators, that are involved in various biological processes, both centrally and peripherally. The prototype member of this group of compounds, anandamide, regulates cell growth, differentiation and death; this holds true also in the skin, that is the largest organ of the body constantly exposed to physical, chemical, bacterial and fungal challenges.

The epidermis is a keratinized multistratified epithelium that functions as a barrier to protect the organism from dehydration, mechanical trauma, and microbial insults, and epidermal differentiation represents one of the best characterized mechanisms of cell specialization.

In this review, we shall summarize current knowledge about the main members of the so-called “endocannabinoid system (ECS)”, in order to put in a better perspective the manifold roles that they play in skin pathophysiology.

In particular, we shall discuss some aspects of the molecular regulation by endocannabinoids of proliferation and terminal differentiation (“cornification”) of mammalian epidermis, showing that ECS is finely regulated by, and can interfere with, the differentiation program.

In addition, we shall review evidence demonstrating that disruption of this fine regulation might cause different skin diseases, such as acne, seborrhoea, allergic dermatitis, itch, psoriasis and hair follicle regression (catagen), making of ECS an attractive target for therapeutic intervention.”

http://www.ncbi.nlm.nih.gov/pubmed/21628127

Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes

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CBD prevents excessive lipogenesis induced by “pro-acne agents&#x...

“Acne vulgaris is the most common human skin disease, affecting quality of life of millions worldwide…

Investigation of the cutaneous cannabinoid system seems to be a promising choice when searching for novel therapeutic possibilities…

“Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris…

These data, together with our current findings, point to a promising, cost-effective, and, likely, well-tolerated new strategy for treating acne vulgaris, the most common human skin disease…

…given the extensively documented accumulation of phytocannabinoids from smoked marijuana in the pilosebaceous unit (where they become incorporated into the hair shaft), it is very likely that CBD can reach the sebaceous glands as well, can accumulate, and may well reach “therapeutically sufficient” concentrations there.

Moreover, it is very important to note that, besides the systemic application, one should keep in mind the possibility of the topical administration.”

 http://www.jci.org/articles/view/64628

“Schematic overview of the cellular “anti-acne trinity” of CBD and its proposed mechanism of action.”

Schematic overview of the cellular “anti-acne trinity” of ...

 

Therapeutic potential of cannabinoid medicines.

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Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

The endocannabinoid system and its therapeutic exploitation.

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“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.”  http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

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

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“The endocannabinoid system (ECS) and the skin. Recent studies have intriguingly suggested the existence of a functional ECS in the skin and implicated it in various biological processes. It seems that the main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced proliferation, 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).

Perspectives in the ECS-targeted management of skin diseases

… preclinical data encourage one to systematically explore whether ECS-modulating drugs can be exploited in the management of common skin disorders…

 … we review preliminary data and discuss the possible applications of ECS-targeted therapies…ECS-targeted approaches in skin diseases. Modulations of the fine-tuned tone of the cutaneous endocannabinoid system (ECS) could have therapeutic values in the management of a large variety of human skin diseases…

Conclusions and future directions in experimental and clinical research

… it is envisaged (this is also strongly supported by pilot studies) that the targeted manipulation of the ECS might be beneficial in a multitude of human skin diseases. However, to predict the real therapeutic potential and translate the exciting preclinical observations discussed earlier into clinical practice, numerous important questions should carefully be addressed. Nevertheless, targeting the cutaneous ECS for therapeutic gain remains an intriguing and provocative possibility warranting future studies.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757311/