e93

Quality of life assessment in skin disorders

Clinical trial

Clin Ter 2019; 170 (2):e93-99.

doi: 10.7417/CT.2019.2116

A therapeutic effect of cbd-enriched ointment in inflammatory
skin diseases and cutaneous scars
B. Palmieri1,2, C. Laurino1,2, M. Vadalà1,2
Department of General Surgery and Surgical Specialties, University of Modena and Reggio Emilia Medical School, Surgical Clinic,
Modena; 2Second Opinion Medical Network, Modena (MO), Italy

1

Abstract
Objective. To investigate the therapeutic effect of CBD-ointment
administered on severe skin chronic diseases and/or on their outcome
scars.
Methods. A spontaneous, anecdotal, retrospective study of 20 patients with two most frequent skin disorders: psoriasis (n: 5 patients),
atopic dermatitis (n: 5) and resulting outcome scars (n: 10). The subjects were instructed to administer topical CBD-enriched ointment tolesioned skin areas twice daily for three months treatment.
Results. Based on skin evaluations (hydration, TEWL, elasticity),clinical questionnaires (SCORAD, ADI, PASI), and supported byphotographic data and investigators’ clinical assessment, the results
showed that topical treatment with CBD-enriched ointment significantly improved the skin parameters, the symptoms and also the PASI
index score. No irritant or allergic reactions were documented during
the period treatment.
Conclusions. The topical administration of CBD ointment, without
any THC, is a safe and effective non-invasive alternative for improve
the quality of life in patients with some skin disorders, especially on
inflammatory background. Clin Ter 2019; 170(2):e93-99. doi: 10.7417/
CT.2019.2116
Key words: CBD, ointment, skin, quality of life

Introduction

Several chronic inflammatory skin disorders, including
atopic dermatitis (or eczema), psoriasis, cutaneous infections, and familial cold autoinflammatory syndrome reducesignificantly the patients’ quality of life, health outcomes
and work productivity (Kimball et al. 2010, Senra andWollenberg 2014, Chisari et al. 2018, Fallari et al. 2016).
Atopic dermatitis (AD) affects 15-30% of children (Shaw etal. 2011, Bieber 2010) and 1-8% of adults, it is characterized by recurrent and often excoriated erythematous patches(papules), associated with severe itching (Guttman-Yassky,
Nograles and Krueger 2011, Leung and Guttman-Yassky2014). The pathogenesis of AD is not fully understood:skin barrier defects driven by a combination of genetic andenvironmental factors (allergen exposure, stress, coloniza-tion or infection of the skin with Staphylococcus aureus or
herpes simplex virus), and immune dysregulation (epidermal intercellular edema, increased numbers of IgE-bearing
Langerhans cells, inflammatory dendritic epidermal cells,
macrophages, eosinophils, and CD4-activated TH2 cells)
have been implicated (Leung and Guttman-Yassky 2014,
Wananukul et al. 2015, Nomura et al. 2003, Leung
2000). AD is often accompanied by allergic rhinitis (75%of children), asthma (15-50%), and food allergy, as well as
conjunctivitis (Wananukul et al. 2015, Simpson 2012). In
contrast, the clinical picture of psoriasis presents erythematous, well-demarcated red plaques covered with white scales
on the scalp, lower back, and extensor aspects of the elbows
and knees, associated with severe pruritus and changes infingernails and toenails (Nickoloff 2001, Guttman-Yassky
et al. 2011). The prevalence of psoriasis, occurred more frequently in women than men, is 0-2% in children and 1-9%
in adults. It is characterized by the presence of neutrophil
overactivation and overproduction of interleukin (IL)-6
and IL-8 from keratinocytes (Komine and Tamaki 2000,
Iannaccone et al 2016). The main triggers for psoriasis
exacerbations are 1) environmental factors, including weight
gain, smoking, alcohol consumption, stress, withdrawal of
corticosteroids, HIV infection, and the use of medications
such as lithium, beta-blockers, or antimalarial agents (Parisi
et al. 2013, Roberson and Bowcock 2010), 2) microbial
factors, (fungi and viruses), e.g. a streptococcal throat infection (Valdimarsson, Sigmundsdottir and Jonsdottir
1997, Prinz 2001), and 3) immune response dysregulation,
including epidermal hyperplasia and altered keratinocyte
differentiation (XSun L. 2014, Lowes, Suarez-Farinas
and Krueger 2014). Both the skin disorders share common
mechanisms of disease, including infiltration of circulating
immune cells in the skin (Guttman-Yassky et al. 2007),
altered expression of proinflammatory cytokines (Nomura
et al. 2003), and variable barrier alterations (Fartasch
1997), and can be recognized as systemic rather than localized cutaneous diseases because skin inflammation isoften complicated by metabolic, cardiovascular and othercomorbidities (Kim and Krueger 2017, Mansouri andGuttman-Yassky 2015). Other chronic inflammatory skindisease is acne vulgaris, resulting from androgen-induced

Correspondence: M. Vadalà. E-mail: mary.vadala@gmail.com. Tel. 3397695748

Copyright © Società Editrice Universo (SEU)

ISSN 1972-6007

e94
increased sebum production, altered keratinization, inflammation, and bacterial colonization of hair follicles on theface, neck, chest, and back by Propionibacterium acnes, andit has a prevalence of 90% among adolescents and 10-15% in
adults (Bhate and Williams 2013, Thiboutot et al. 2009).
These inflammatory acne lesions can result in permanentdisfiguring sequelae (acne scars), that can be classified in two
basic types: atrophic and hypertrophic scars, depending onwhether there is a net loss or gain of collagen (Fabbrocini
et al. 2010). Regard the prevalence, minor scarrings occur
in up to 95% of the patients, while more severe scarrings
occur in up to 22% of patients (mostly aged 25-44 years)(Layton, Henderson and Cunliffe 1994).
The traditional systemic treatments (e.g. methotrexate,
cyclosporine for psoriasis) present often some limitations,
including cumulative toxicity of target organs and potential
drug interactions (McClure, Valentine and Gordon 2002,
Christophers et al. 2006, Ferrandiz, Carrascosa and Boada 2010). In recent years, several researchers analyzed theuse of cannabinoids in the treatment of these dermatologic
disorders, including also melanoma and nonmelanoma skincancer, melasma, and seborrheic dermatitis, and reported
its anti-inflammatory properties and inhibitory effect on
rapidly proliferating tumorigenic cell lines (Mounessa et
al. 2017, Kogan 2005).
The cannabinoids or phytocannabinoids, e.g. cannabidiol(CBD), cannabichromene (CBC), cannabigerol (CBG),
cannabinol (CBN) and delta (9)-tetrahydrocannabinol (Δ9-THC), are the active constituents of the plant Cannabis
sativa, and elicit their activity by binding to specific receptors: the CB1 and CB2 cannabinoid receptors [foundon neurons and glial cells and in spleen tissue, respectively(Van Sickle et al. 2005, Munro, Thomas and Abu-Shaar1993)] that are part of the G-protein coupled class and theiractivation results in inhibition of adenylate cyclase activity(Baker et al. 2003, Iversen 2003, Di Marzo, Bifulco and
De Petrocellis 2004).
However, the CBD exerts multiple pharmacologicalactions via no-CB1 and no-CB2 receptors, but by bindingtransient receptor potential vanilloid type 1 (TRPV1) (Costa
et al. 2004), G protein-coupled receptor 55 (GPR55) (Pertwee et al. 2010, Pertwee 2007), and 5-hydroxytryptamine
receptor subtype 1A (5-HT1A) (Russo et al. 2005).
Currently, CBD is a widespread ingredient in skin careproducts formulated as body oils, moisturizers, lotions andlip balms (Anwar F. 2006), but scientific studies on topicalsafety and efficacy of this extract are lacking.
Therefore, we investigated, in spontaneous, anecdotal,
retrospective study, the therapeutic effect of CBD-ointment
administered on severe skin chronic diseases and/or on theiroutcome scars.

Materials and methods

We reviewed medical records (electronic or paper-based)of 20 patients that had appealed to our “Second Opinion
Medical Consulting Network”, Medical Centre (Modena,
Italy), between September 2016 and January 2017, because
of inflammatory skin disorders and cutaneous scars/blemi-

B. Palmieri et al.
shes. The Second Opinion Medical Network is a consultationreferral web and Medical Office System recruiting suddenly
a wide panel of real-time available specialists, to whom
any patient affected by any disease or syndrome and notadequately satisfied by the diagnosis or therapy can apply
for an individual clinical audit (Wunsch A. 2013). Due tothe doctor-patient communication gap, most of the patientsusually wander around the medical websites looking forproper answers to their health problems. However, theirsearch often becomes compulsive and obsessive and often
ambiguous and frustrating (Palmieri B. 2017). Palmieri etal. (Palmieri et al. 2011) describe this borderline or even pathological behaviour as the “Web Babel Syndrome” – a psychological imbalance affecting young and elderly patients,
especially those with multiple synchronous diseases who
receive from their caregivers heterogeneous and misleading
informations or advices, including confused, contradictory
statements and prescriptions (Palmieri and Iannitti 2011).
To deal with this problem, the Second Opinion Network aims
to be a useful “problem-solving” support revisiting eachdiagnostic and therapeutic step and properly re-addressing
tailored treatments and prognoses, as well as preventing
unnecessary investigational procedures and unhelpful andexpensive medical and surgical interventions (Di Cerbo
and Palmieri 2012).
In this preliminary investigation, we adopted selective
inclusion criteria: 1) suffering from moderate/severe skindisorders for at least 6 months and seeking an effective,
adequate therapy; and specific exclusion criteria: 1) pregnant
or breastfeeding women, 2) topical medication containing
steroids for the treatment of skin disease for at least one
month, 3) skin intolerance/allergies to the components ofproduct used in the study.
Twenty volunteers (14 females and 6 males) between
20 and 80 years of age (Fig. 1), were visited and informed
during a personal interview, gave their permission, andsigned an informed consent previously approved by the
Local Institutional Review Board, in accordance with theHelsinki Declaration. These patients were complaining of thetwo most frequent skin disorders: psoriasis (n: 5 patients),
atopic dermatitis (n: 5) and resulting scars (n: 10) (Fig.2).
The product, hemptouch organic skin care ointment (Hemptouch Ltd, Novo mesto, Slovenia) contained CBD seed oiland natural ingredients, including Mangifera Indica, Calendula officinalis, Lavendula officinalis, Chamomile, Amyris
Balsamifera, and butyrospermum (shea butter) (Tab.1) The
subjects were instructed to administer topical ointment tolesioned skin areas twice daily, in morning and evening, forthree months treatment. During this period, the patients not
utilized any skin care product. We performed the following
skin evaluations:a) Hydration and transepidermal water loss (TEWL)
assessment at baseline and after three months treatment witha DermaLab® USB instrument (Cortex Technologies, Hadsund, Denmark), this Point of care (POCT) with hydration
probe, that is pressed upon the skin, relies upon the conductance principle, which measures the water binding capacityof the stratum corneum (Laurino, Palmieri and Coacci2015). TEWL is defined, instead, as a measurement of thequantity of water that passes from inside a body through theepidermal layer to the surrounding atmosphere via diffusion

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Quality of life assessment in skin disorders

Skin parameters were measured on five selected areas:
forehead (F), right and left malar area (RMA and LMA, respectively), and right and left lateral-medial area of the neck
(RN and LN, respectively). We assessed also the elasticityof the forearm (FO) as control, according to the manufacturer’s instructions, since skin arm elasticity changes lessquickly then skin face elasticity. The value of hydration[(expressed in microSiemens units (μS)], TEWL (measured
by diffusion gradient in g/m2/h) and elasticity (expressedin μS) is the arithmetic mean of 3-5 repetitive measures inthe same area.

Statistical analysis

The statistical analysis was performed using the MannWhitney test (continuous variables not normally distributed)
and the chi-squared test (categorical variables). Statisticalsignificance was set at a P value < 0.05, and all data andgraphics were analyzed using the R software, version 3.1.2(2015, Vienna, Austria) (RA. 2015).

Results

Tab. 1. Components of skin care ointment 50 ml/1.69 floz.
Composition of CBD-ointment
Component
Mangifera Indica
Calendula officinalis
Lavendula officinalis
Chamomile
Amyris Balsamifera

Concentration mg/ml
N/A
N/A
N/A
N/A
N/A

and evaporation processes, which is physiologically reduced
during age (Elias 2005).
b) Elasticity assessment at day 0 and day 90 with ElastiMeter® (Delfin Technologies, Kuopio, Finland), it wasmeasured as stiffness, a physical measure of an object’s
resistance to change in shape under an external force in N/m.
The device consists of a 1 mm length indenter, a reference
plate and built-in force sensors. The probe head is quicklypressed against the skin surface with a recommended standard pressure that is displayed on the screen. The indenter
induces a constant deformation when the reference plate isin full contact with the skin, and the elasticity is determined by the skin resistance to this deformation (Iivarinen,
Korhonen and Jurvelin 2014).
c) Photographic assessment at baseline (day 0), day 30,
day 60 and day 90.
d) We also use several questionnaires to evaluate thedegree of the symptoms, including Scoring Atopic Dermatitis (SCORAD) index for atopic dermatitis, Acne disability
Index (ADI) for acne, and Psoriasis Area Severity Index(PASI), index used to express the severity of psoriasis.

After a treatment period of three months, the evaluatedskin parameters significantly improved in all the patients.
Specifically, the hydration (p< 0.01) increased of 6.9% in F
area, 6.1% in RMA, 6.5% in LMA, 6.8% in RN and 5.5% in
LN (Fig.3). TEWL also significantly improved (p < 0.001)
in these selected sites: increase of 28.1% in F area, 20.7%
in RMA, 23.7% in LMA, 17.6% in RN and of 24.7% in LN(Fig.4). At last, elasticity (p < 0.001) improved of 17.1% in
F field, 27.1% in RMA, 23.2% in LMA, 22.9% in RN ande96

B. Palmieri et al.
6-8). Additionally, we recorded reductions in the numbersof papules (−20%), pustules (−31%) in dermatologicalpatients. The topical ointment was significantly (p< 0.001)
efficacious in improving also PASI index score (excluding
the head, which was not treated) at day 90.
Fig. 6-8: Photography of cutaneous blemishes (sunspots)on the right leg (Fig.6), and right arm (Fig.7) of the patient(woman, 73 aa), and scar (Fig.8) due a cyst removal surgery(men, 78aa) before and after 3 consecutive months of twicedaily application of the study cream.

of 26.1% in LN area (Fig.5). Unretouched photos taken
before treatment and after 12 weeks of treatment showed asignificant reduction of major signs of cutaneous blemishes
in a woman (73 aa) and of scar due a cyst removal surgery
in the men (78 aa), confirming significant improvement inthese symptoms and none experiencing worsening (Fig.

Fig. 6

Fig. 8Discussion

Several studies evidenced that topical route of CBDadministration represents significant therapeutic tool in thetreatment of chronic conditions, encephalomyelitis (EAE),
multiple sclerosis (MS), with less side effects because due toFig. 7

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Quality of life assessment in skin disorders
the lower peak plasma levels (Lodzki et al. 2003, Touitou E1988). For istance, Giacoppo et al, showed that a preparationof 1% CBD-cream reduces the expression of Nitrotyrosine(iNOS) in tissues from EAE treated C57BL/6 mice, suggesting that plant-derived cannabinoids (CBD, THC, CBN),may be responsible for the reduction of cytokines production, that in turn counteract the rise of iNOS levels and thedownstream cascade of events triggered by the inflammatory
process, reducing thus oxidative stress (Giacoppo et al.
2015). Indeed, published studies evidenced that THC may
inhibite the proliferation of mouse lymphocytes and decrease the production of interleukin-2 (IL-2) and interferon-c(IFNc) (Klein et al. 2000, Klein, Newton and Friedman
2001, Klein et al. 1985); but also may reduce the secretionof pro-inflammatory cytokines like IL-1a, IL-1b and tumor
necrosis factor-alpha (TNFa) in microglial cells. In anotherstudy, CBD and CBN were shown to exert a suppressive
effect on human keratinocyte proliferation. Here, the synthetic CB receptor agonists HU-210, a structural analogueof THC, displayed an inhibitory effect on cell proliferation,clearly confirming the anti-inflammatory activity of thecannabinoids beyond its interaction with specific CB1 andCB2 receptors. This is reminiscent of palmitolylethanolamide (PEA), an endogenous fatty acid with cannabimimetic
properties that attenuates skin inflammation, although it does
not bind to CB1 or CB2 receptor (Stander, Reinhardt andLuger 2006, Jordt et al. 2004).
Our results showed that topical treatment with CBDenriched ointment significantly improved the quality of lifeof patients with several skin diseases.
The mean skin elasticity level on baseline visit was 46µs, whereas at the end of study, the same value was increased
gradually (70 µs). This effect may be due to essential fatty
acids, including α- linolenic acid, γ-linolenic acid, linoleic
and oleic acids, and phytosterols (β-sitosterol) (Dobrev
2007, Zaman S 2012), present in the used topical cream,that may inhibit the enzyme 5-α-reductase, subsequently
inhibiting the excessive skin sebum secretion and improving
elasticity and hydration.
No irritant or allergic reactions were documented during
the period treatment. A topical product also improved severityof itch and loss of sleep in the AD patients. Gaffal et al, demonstrated that CBD application may attenuate ovalbumininduced allergic airway inflammation in experimental mousemodel of atopic dermatitis (C57Bl/6 mice) as indicated by areduced number of lung-infiltrating immune cells and of theserum IgE and IgG levels (Gaffal et al. 2013).
We observed also antiproliferative and antinflammatory
effects of CBD treatment in patients with acne scars. These
effects could be associated to specific sebostatic actions of
CBD: a) normalize the pathologically elevated lipogenesis
induced by “pro-acne” agents, b) suppresse cell proliferation and c) prevent the actions of toll-like receptor (TLR)
activation or “pro-acne” agents to elevate proinflammatory
cytokine levels (Olah et al. 2014). This is especially promising, because the currently available,anti-acne agent,isotretinoin (accutane), is known to cause serious side
effects, including hypertriglyceridemia, hepatotoxicity, andmood changes, e.g depression and psychosis (Kurokawa et
al. 2009, Ellis and Krach 2001, Rigopoulos, Larios and
Katsambas 2010).

Our results showed clearly that cannabinoids inhibitedthe proliferation of keratinocytes, thus demonstrating a therapeutic potential as well for the treatment of psoriasis, but
further investigation is urgently needed to identify its actions
mechanism. To date, the literature on human CBD safety andpharmacokinetics is lacking, however, given the extensively
documented accumulation of phytocannabinoids from smoked cannabis in the pilosebaceous unit (e.g hair, sebaceous
gland) (Kintz, Cirimele and Mangin 1995, Skopp et al.
2007), it is expected that CBD, due to its high lipophilicity,
may reach and accumulate in the sebaceous glands, via thetransfollicular route (Lodzki et al. 2003, Tubaro et al. 2010,
Hueber, Wepierre and Schaefer 1992). This accumulation
is been evidenced for several topically applied lipophiliccompounds, including steroid hormones, photosensitizers(Hueber et al. 1992, Togsverd-Bo K 2012).
Main limitations of our study include the uncontrolled
and retrospective design study and the small clinically heterogeneous cohort.
Conclusions

The topical administration of CBD ointment, without
any THC, is a safe and effective non invasive alternative
for improve the quality of life in patients with some skindisorders, especially on inflammatory background.
In a next future, further trials on safety, tolerability andefficacy of topical cannabinoids combining CBD and THC
but also cannabis terpenes and other plant extracts, would
give us definite informatons about the most effective integrated formula of this sort of panacea in the dermatologicalsetting.
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