WO2019186544A1

WO2019186544A1 - Topical cannabidiol compositions and methods for protecting the skin from ultra-violet radiation

Info

Publication number: WO2019186544A1
Application number: PCT/IL2019/050341
Authority: WO
Inventors: Raphael Luxenbourg; Martine LUXENBOURG
Original assignee: Individual
Current assignee: Individual
Priority date: 2018-03-26
Filing date: 2019-03-26
Publication date: 2019-10-03
Anticipated expiration: 2020-09-26

Abstract

The present invention relates, in some embodiments thereof, to cannabidiol (CBD) and compositions comprising same for use in protecting the skin of a subject from UV radiation-associated damage. The present invention further relates to cannabidiol (CBD) and compositions comprising same for use in attenuating UV radiation-induced cellular apoptosis.

Description

TOPICAL CANNABIDIOL COMPOSITIONS AND METHODS FOR PROTECTING THE SKIN FROM ULTRA-VIOLET RADIATION

FIELD OF THE INVENTION

BACKGROUND OF THE INVENTION

It has long been known that prolonged exposure to UV radiation can damage the skin. Prolonged skin exposure to sun light is commonly associated with the formation of sunburns as well as with an increased incidence of skin cancers, and accelerated skin aging. Even though UV rays make up only a very small portion of the sun’s rays, they are the main cause of the sun’s damaging effects on the skin. UVA rays are mostly linked to long term skin damage, such as wrinkles, but they are also thought to play a role in some skin cancers. UVB rays have slightly more energy than UVA rays. They can damage skin cells’ DNA directly and are the main rays that cause sunburns. UVB rays are also considered as the main factor that causes most skin cancers. UVC rays have more energy than the latter UV rays, but they do not penetrate the earth atmosphere.

Various sunscreen formulations for counteracting UV radiation are known. These sunscreen products can be grouped into two main categories, i.e., organic and inorganic sunscreens.

Various sunscreen formulations of organic UV absorbers are known. The most widely used organic-based sunscreens include, inter alia, paraaminobenzoic acid (PABA), PABA esters (glyceryl PABA), amyldimethyl PABA and octyldimethyl PABA, benzophenones (oxybenzone and sulisobenzone), cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (homomethyl salicylate), anthranilates such as menthyl anthranilate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5- sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, and 2-ethyl-2-cyano-3,3'-diphenyl acrylate.

Known organic sunscreen agents may be associated with limited effectiveness as UV protectants, in terms of SPF (Sun Protection Factor), and commonly exhibit a relatively high allergenic potential. Concern has also been recently raised as to whether the known organic sunscreens chemical components are indeed inert.

Physical or inorganic based sunscreens include inter alia, titanium dioxide and zinc oxide. Those compounds are considered to effectively block UV radiation. Nevertheless, inorganic-based sunscreen formulations are white and produce an opaque appearance on the skin and even with advanced formulations containing very small ZnO and T1O2 particles, the opaqueness is still an issue for those who prefer invisible protection. Moreover, such inorganic compounds have been suspected to generate toxic radicals under the influence of light and water and are not readily washed off from the body. As such, these sunscreen products are deemed cosmetically unacceptable by many consumers.

There thus remains a need for novel, non-toxic sunscreen compositions that will effectively block UV radiation and protect the skin from the damaging effects of prolonged exposure to UV radiation.

SUMMARY OF THE INVENTION

The present invention relates, in some embodiments, to methods and compositions effective in protecting the skin from damages associated with over exposure to UV radiation. The present invention is based in part, on the unexpected discovery that cannabidiol (CBD) effectively attenuates UV radiation-induced apoptosis of skin cells.

Advantageously, CBD based compositions for use as sunscreen agents are safe and efficacious, even without the addition of known sunscreen agents.

According to some embodiments, the herein disclosed compositions are substantially free, essentially free or free of an inorganic sunscreen agent. According to some embodiments, the herein disclosed compositions are substantially free, essentially free or free of titanium dioxide and/or zinc oxide.

According to some embodiments, the herein disclosed compositions are substantially free of an organic sunscreen agent other than CBD.

According to some embodiments, the organic sunscreen agent is selected from the group consisting of paraaminobenzoic acid (PABA), PABA esters (glyceryl PABA), amyldimethyl PABA and octyldimethyl PABA, benzophenones (oxybenzone and sulisobenzone), cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (homomethyl salicylate), anthranilates such as menthyl anthranilate, 2-ethylhexyl-2- cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5-sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, and 2-ethyl-2-cyano-3,3'-diphenyl acrylate.

According to one aspect, the present invention provides a composition comprising a cannabidiol (CBD), and a pharmaceutically acceptable carrier or excipient for use in protecting skin of a subject in need thereof from damages associated with exposure to UV radiation.

According to yet another aspect, the present invention provides a method of protecting skin of a subject in need thereof, from damages associated with exposure of the subject to UV radiation, the method comprising topically administering to the subject a composition comprising a cannabidiol (CBD), and a pharmaceutically acceptable carrier or excipient.

According to yet another aspect, the present invention provides a method of protecting skin of a subject in need thereof, from damages associated with exposure of the subject to ultraviolet (UV) radiation, the method comprising topically administering to the subject a topical composition comprising a cannabidiol (CBD), and a pharmaceutically acceptable carrier or excipient, wherein the composition is substantially free of an additional sunscreen agent.

According to some embodiments, the composition is useful in preventing, attenuating or blocking the harmful effects of UV radiation. According to some embodiments, the composition is useful in inhibiting caspase 3 expression in cells exposed to UV radiation.

According to some embodiments, the CBD is provided in an amount of about 0.5% to about 10% by weight of the composition. According to some embodiments, the CBD composition includes a liquid wax. According to some embodiments, the liquid wax is jojoba oil.

According to some embodiments, the UV radiation is solar UV radiation. According to some embodiments, the UV radiation is from a manmade source. According to some embodiments, the man-made source of UV radiation is selected from sunlamp, sunbed, and UV therapy.

According to some embodiments, the CBD is capable of attenuating UV-induced skin cells apoptosis.

According to some embodiments, the CBD is provided within a natural cannabis plant extract. According to some embodiments, the CBD is present within the composition as a highly purified extract of cannabis which comprises at least about 90% (w/w) CBD in the extract. According to some embodiments, the CBD is a crystalized form of CBD produced from cannabis sativa L. According to some embodiments, the CBD is present within the composition as a synthetic compound.

According to some embodiments, the composition further comprises at least one of a sunscreen agents.

According to some embodiments, the sunscreen agent is selected from an organic and an inorganic sunscreen agent. According to some embodiments, the organic sunscreen agent is selected from the group consisting of: paraaminobenzoic acid (PABA), PABA esters (glyceryl PABA), amyldimethyl PABA, octyldimethyl PABA, benzophenones (oxybenzone and sulisobenzone), cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (homomethyl salicylate), anthranilates, menthyl anthranilate, 2-ethylhexyl-2- cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5-sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, and 2-ethyl-2-cyano-3,3'-diphenyl acrylate. According to some embodiments, the inorganic sunscreen agent is titanium oxide or zinc oxide.

According to some embodiments, the CBD is a derivative of CBD.

According to some embodiments, the UV radiation is selected from UVA and UVB. According to some embodiments, the UV radiation is UVB having rays of wavelengths between 290 and 320 nm.

. According to some embodiments, the composition is formulated for topical administration or application. According to some embodiments, the CBD provided in an amount of at least about 6 x 10 ³ pg/cm² and wherein the amount of CBD attenuates apoptosis at least about 2 times higher as compared to a control subject.

According to yet another aspect, the present invention provides a composition comprising CBD and a pharmaceutical applicable carrier or excipient, for use in preventing or attenuating UV radiation-induced apoptosis in a cell.

According to yet another aspect, the present invention provides a method of preventing or attenuating UV radiation-induced apoptosis in a cell, comprising administering to the cell a composition comprising CBD and a pharmaceutically applicable carrier or excipient.

According to some embodiments, the cell is a skin cell. According to some embodiments, the skin cell is an epidermis skin cell selected from keratinocyte, melanocyte, merkel cell, and langerhans cell.

According to some embodiments, administering to the cell is incubating the cell with a composition comprising CBD and a pharmaceutically applicable carrier or excipient.

According to some embodiments, the CBD is provided as a natural cannabis plant extract. According to some embodiments, the CBD is present as a highly purified extract of cannabis which comprises at least 90% (w/w) CBD. According to some embodiments, the CBD is a crystalized form of CBD produced from cannabis sativa. According to some embodiments, the CBD is present as a synthetic compound. According to some embodiments, the composition further comprises at least one of a sunscreen agents. According to some embodiments, the CBD is a derivative or an analog of CBD.

According to yet another aspect, the present invention provides a sunscreen composition comprising a cannabidiol (CBD); and a pharmaceutically acceptable carrier or excipient.

According to some embodiments, the CBD is provided as a natural cannabis plant extract. According to some embodiments, the CBD is present as a highly purified extract of cannabis which comprises at least 90% (w/w) CBD. According to some embodiments, the CBD is a crystalized form of CBD produced from cannabis sativa L. According to some embodiments, the CBD is present as a synthetic compound.

According to some embodiments, the composition further comprises at least one of a sunscreen agents. According to some embodiments, the CBD is a derivative or an analog of CBD.

According to some embodiments, the composition is useful in protection from UV radiation. According to some embodiments, the UV radiation is selected from UVA and UVB. According to some embodiments, the UV radiation is UVB having rays of wavelengths between 290 and 320 nm.

According to some embodiments, the composition is formulated for topical administration.

Unless otherwise defined, all technical or/and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods or/and materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a dot plot demonstrating the viability of a skin, as measured utilizing an MTT assay, following 48 hours exposure to increasing concentrations of CBD.

FIG. 2 is a bar graph showing the UVB protective effect of CBD when applied onto a skin at increasing concentrations, as measured by a caspase-3 activity assay (n=3; *p<0.05).

It should be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements are exaggerated relative to each other for clarity. Further, where considered appropriate, reference numerals have been repeated among the figures to indicate corresponding elements.

DETAIFED DESCRIPTION OF THE INVENTION

It is understood that the invention is not limited to the particular methodology, devices, items or products etc., described herein, as these may vary as the skilled artisan will recognize. It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only and is not intended to limit the scope of the invention. The invention is not limited to the specifically described products and methods and may be adapted to various applications without departing from the overall scope of the invention. All ranges disclosed herein include the endpoints. The use of the term“or” shall be construed to mean“and/or” unless the specific context indicates otherwise.

Prolonged exposure of the skin to ultraviolet radiation, particularly UVB and UVA may cause critical damage to the epidermis which may result in a skin disorder or condition such as skin erythemas, light dermatoses, and even skin cancer.

Cannabinoids are a group of chemicals known to activate cannabinoid receptors in cells. CBD is considered to have a wide scope of potential medical applications. CBD has been clinically reported to lack side effects, particularly lack psychoactivity (as is typically associated with A9-THC), and non-interference with several psychomotor learning and psychological functions.

It has been surprisingly found by the inventors of the present invention that the cannabinoid cannabidiol (CBD) possesses UV blockage effect. It has been further surprisingly found that CBD is useful in the prevention/attenuation of cellular apoptosis induced by UV radiation.

As described herein, the application of the cannabinoid cannabidiol (CBD) onto skin was found to be efficacious in attenuating the detrimental effect of UV radiation to skin. It has been found that CBD is useful in attenuating UV induced apoptosis of skin cells.

Thus, the present invention relates, in one aspect, to CBD or compositions comprising same for use in protecting the skin of a subject against UV radiation. The present invention provides, in a further aspect, CBD or a composition comprising same for use in attenuating UV induced apoptosis in a cell. The present invention provides, in yet a further aspect, a sunscreen composition comprising CBD and a pharmaceutical acceptable excipient or carrier. The present invention provides, in yet a further aspect, a method of protecting the skin of a subject in need thereof from UV radiation, the method comprising topically administering a therapeutically effective amount of a composition comprising CBD or a derivative thereof onto the skin of the subject. Cannabis is a genus of flowering plant that produces a group of chemicals called cannabinoids, among them the cannabidiol (CBD). Known species of cannabis plants include the subspecies, sativa, indica, and ruderalis.

According to some embodiments, the CBD is in a substantially pure form. According to some embodiments, the CBD within the composition of the invention, is provided as an extract prepared from at least one cannabis plant, wherein the CBD is highly purified from the extract of cannabis.

As used herein the term "highly purified extract" refers to an extract wherein the w/w percent of CBD in the extract is at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 98% of the total extract. The substantially pure CBD used of the invention is substantially free of any other naturally occurring or synthetic cannabinoids, including cannabinoids that occur naturally in cannabis plants. In this context, "substantially free" can be taken to mean that no cannabinoids other than CBD are detectable by HPLC. According to some embodiments, the extract comprises less than 0.15% THC. According to some embodiments, the extract comprises up to 1 % of a CBD derivative, e.g., cannabidivarin (CBDV).

According to some embodiments, the CBD is in an isolated form. According to some embodiment, the CBD is isolated from a cannabis plant. According to some embodiments, the CBD is in a crystalized form (e.g., a solid powder). According to some embodiments, the CBD is purified/isolated from a cannabis plant selected from the group consisting of: sativa, indica, and ruderalis. According to some embodiments, the cannabis plant is sativa L.

The highly purified CBD may be produced by various materials and methods. According to some embodiments, the CBD extract from at least one cannabis plant is produced by extraction with supercritical or subcritical C0₂. Alternatively, the CBD extract from at least one cannabis plant is produced by contacting plant material with a heated gas at a temperature which is greater than l00°C, sufficient to volatilize one or more of the cannabinoids in the plant material to form a vapor and condensing the vapor to form an extract. According to some embodiments, the CBD may be isolated or purified by phase transfer catalysts or by column chromatography. The column chromatography may be performed with ethanol and ether extracts of hemp on alumina, yielding two major fractions: (1) chlorophyll, CBD, and CBN, and (2) THC which are separated using a column chromatography.

As used herein, the term“isolated" refers to the CBD when separated from at least some of the components with which it is usually associated in nature, and/or prepared or purified by a process that involves the hand of a man.

According to some embodiments, the CBD is a synthetic form. Synthetic cannabinoids are chemicals with similar structures and functions to plant cannabinoids or endocannabinoids.

The scope of the invention also extends, according to some embodiments, to derivatives of CBD that substantially retain the desired activity of protecting the skin against the harmful effect of UV radiation or attenuating cellular apoptosis induced by exposure to UV radiation. Derivatives that retain substantially the same activity as the starting material, or more preferably exhibit improved activity, may be produced according to standard principles of medicinal chemistry, which are well known in the art. Such derivatives may exhibit a lesser degree of activity than the starting material, so long as they retain sufficient activity to be therapeutically or cosmetically effective. Derivatives may exhibit improvements in other properties that are desirable in pharmaceutically or cosmetically active agents such as, for example, improved solubility, reduced toxicity, enhanced uptake, reduced volatility, etc. Known derivatives of CBD include CBDA, CBD- dimethyl heptyl, cannabidivarin (CBDV), and abnormal CBD. Optionally, the herein disclosed composition is substantially free, essentially free or free of a CBD derivate According to some embodiments, CBD derivative includes at least about 70%, 80%, 90%, or 95% molecular similarity to natural CBD. Each possibility refers to a separate embodiment of the invention. According to some embodiments, a derivative of CBD that substantially retain the herein disclosed activity of CBD is a derivate that retains at least 60%, 70%, 80%, 90% or 95% of the activity of CBD. Each possibility refers to a separate embodiment of the invention.

As used herein the term "UV radiation" refers to UV radiation of the sunlight and/or to artificial UV radiation (or man-made UV radiation). Ultraviolet (UV) is an electromagnetic radiation with a wavelength that ranges from 10 nm (30 PHz) to 400 nm (750 THz). The UV radiation has been arbitrarily divided into a number of regions, among them are UVA, UVB and UVC. The UVA radiation, which extends between 315 nm and 400 nm, can cause sunburns, but its capacity to do so is less than that of UVB radiation. The UVB radiation extends from 280 nm to 320 nm. It is the principal cause of the sunburn reaction and it is also the most effective in stimulating the tanning reaction in the skin. UVC radiation (100 nm-280 nm) from the sun does not reach the surface of the earth.

According to an aspect of the present invention, there is provided a CBD or a formulation comprising same for use in protecting skin of a subject in need thereof against UV radiation.

According to yet another aspect, the present invention provides a method for protecting the skin of a subject in need thereof, the method comprising the step of topically administering to a subject in need thereof a therapeutically effective amount of a composition comprising CBD or a derivative thereof.

According to yet another aspect, the present invention provides a method of preventing a skin damage associated with exposure of the skin to UV radiation, the method comprising the step of topically administering to a subject in need thereof a therapeutically effective amount of a composition comprising CBD or a derivative thereof.

According to yet another aspect, the present invention provides a method of preventing a skin damage associated with prolonged exposure of the skin to UV radiation, the method comprising the step of topically administering to a subject in need thereof a therapeutically effective amount of a composition comprising CBD or a derivative thereof. In accordance with those embodiments, CBD is capable of protecting against and/or blocking UV radiation and/or damage associated therewith. As used herein the terms "protecting" and "protection" are interchangeable with the term "preventing" and may further encompass the terms "blocking", "attenuating" and/or "absorbing", and/or "retarding", and/or "treating". By "protecting" the skin against UV radiation it is meant also to protecting from potential damages to the skin as a result of prolonged exposure to UV radiation. The term also refers to blocking UV radiation and by that preventing potential skin damages.

As used herein the term "harmful effects of UV radiation" or "UV radiation- associated damage" refers to any effect, condition or disease caused by prolonged exposure of the skin to sunlight or to artificial UV radiation. Harmful effects of UV radiation may include, without limitation erythema, light dermatoses, skin cancers, and accelerated skin aging (e.g., wrinkles). Each possibility refers to a separate embodiment of the invention.

As used herein the term "Erythema" refers to redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. One of the causes to Erythema is solar radiation (sun -burn).

As used herein the term "accelerated skin aging" refers to any skin appearance associated with aging that is also considered to be connected to exposure to UV radiation. The term, inter alia, refers to appearance of wrinkles, age spots and dryness.

As used herein the term "skin cancer" refers to cancers that arise from the skin. Non limited types of skin cancers include, basal-cell skin cancer (BCC), squamous-cell skin cancer (SCC) and melanoma.

As used herein the term "a subject not being subjected to CBD application" has the meaning of a subject not being exposed to or treated with CBD. The term encompasses a subject not being treated with a sunscreen agent other than CBD. The term is interchangeable with the term "control" and refers to subjects treated with a similar composition without any CBD.

As used herein, the phrase“effective amount” and“therapeutically effective amount” describes an amount of the CBD and/or derivative thereof that is sufficient to substantially attenuate, filter, block, absorb or prevent the occurrence of skin damage associated with exposure to UV radiation. As used herein the term "subject" refers to a mammal, specifically to a human subject. Optionally, the subject is a healthy subject, i.e., a subject that was not diagnosed as having a dermatological disorder. Non-limiting examples of dermatological diseases include eczema, psoriasis, sunburn, contact dermatitis, conditions caused by toxic materials (e.g., plant material), type 1 and type 2 herpes, insect bites, anal itching, vaginal itching, acne, warts and other acute and chronic dermatoses afflicting humans.

According to yet another aspect, the present invention provides CBD or a composition comprising same, for use in attenuating cellular apoptosis induced by exposure of the cells to UV radiation.

According to yet another aspect, the present invention provides a method of attenuating/inhibiting apoptosis induced by exposure of the cells to UV radiation, comprising administering to the cells a composition comprising CBD. In one or more embodiments, the application of the herein disclosed CBD-based composition is prior to and/or at about the time of exposure to UV radiation.

According to some embodiments, CBD effectively attenuates apoptosis of cells. According to some embodiments, CBD inhibits caspase 3 expression in cells exposed to UV radiation. According to some embodiments, the cells are epidermal cells, or dermal cells. According to some embodiments, the epidermal cell is selected from the group consisting of keratinocytes, melanocytes, merkel cells, and langerhans cells. According to some embodiments, the CBD attenuates apoptosis by at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or by 100%. Each possibility refers to a separate embodiment of the invention.

According to some embodiments, CBD attenuates apoptosis by at least about 1.2, 1.3, 1.4., 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5-fold, or any value in between, as compared to control or vehicle treated cells. Each possibility refers to a separate embodiment of the invention. According to some embodiments, the CBD in an amount of at least about 6xl0 ⁶ pg/crrr attenuates apoptosis by at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or by 100%. Each possibility refers to a separate embodiment of the invention. According to some embodiments, CBD in an amount of at least about 6xl0 ⁶ pg/cm² attenuates apoptosis by at least about 1.2, 1.3, 1.4., 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5-fold, or any value in between, as compared to control or vehicle treated cells. Each possibility refers to a separate embodiment of the invention.

According to some embodiments, the CBD in an amount of at least about 6xl0 ³ pg/cm² attenuates apoptosis by at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or by 100%. Each possibility refers to a separate embodiment of the invention. According to some embodiments, CBD in an amount of at least about 6xl0 ³ pg/cm² attenuates apoptosis by at least about 1.2, 1.3, 1.4. ,1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5-fold, or any value in between, as compared to control or vehicle treated cells. Each possibility refers to a separate embodiment of the invention.

According to some embodiments, the CBD in an amount of at least about 6 or 60 pg/cm² attenuates apoptosis by at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or by 100%. Each possibility refers to a separate embodiment of the invention. According to some embodiments, CBD in an amount of at least about 6 or 60 pg/cm² attenuates apoptosis by at least about 1.2, 1.3, 1.4., 1.5, 2, 2.5, 3, 3.5, 4, 4.5 or 5-fold, or any value in between, as compared to control or vehicle treated cells. Each possibility refers to a separate embodiment of the invention.

According to some embodiment, the method includes incubating the cells with a composition comprising CBD for a period a few minutes, a few hours and up to a few days, for example, one day, two days, three days or more, or any value in between.

According to some embodiments, the CBD is at an amount that ranges between about 6xl0 ⁶ and about 60pg/cm². The CBD may be provided in amounts higher than 6xl0 ⁶ or about 60pg/cm². According to some embodiments, when the CBD is provided at 60pg/cm², apoptosis is attenuated by at least about 4 times more as compared to cells or skin without CBD treatment (or control). According to some embodiments, when the CBD is provided at 6 pg/cm², apoptosis is attenuated by at least about 3 times more as compared to cells or skin without CBD treatment. According to some embodiments, when the CBD is provided at 0.6 pg/cm², apoptosis is attenuated by at least about 2 times more as compared to cells or skin without CBD treatment. According to some embodiments, when the CBD is provided at 0.06 pg/crrr to 6 x 10 ³ pg/cm², apoptosis is attenuated by at least about 2 times more as compared to cells or skin without CBD treatment. According to some embodiments, when the CBD is provided at 6 x 10⁴ pg/cm² to 6 x 10⁶ pg/cm², apoptosis is attenuated by at least about 1.5 times more as compared to cells or skin without CBD treatment.

According to yet another aspect, the present invention provides a sunscreen formulation comprising CBD, or pharmaceutically acceptable salts or derivatives thereof, formulated into pharmaceutical dosage forms, together with suitable pharmaceutically acceptable carriers, which is capable of effectively attenuating UV radiation.

As demonstrated herein below, CBD did not show cytotoxic cellular effect. Hence, advantageously, the sunscreen composition which is based on CBD does not cause adverse chemical reactions upon the application onto the skin of the user. Further advantageously and without being bound by any theory or mechanism of action, CBD attenuates UVB radiation as possessing a potent anti-oxidant activity. Some embodiments of the invention refer to CBD as a sunscreen agent that does not physically block the UV radiation. Alternative embodiments of the invention refer to CBD as a sunscreen agent that does physically block the UV radiation.

As used herein the term "sunscreen" is interchangeable with the terms screening agent, UV radiation absorbing agent, UV protecting agent, UV absorbing agent, UV filtering agent and UV blocking agent.

As used herein dermatologically acceptable carriers include, for example, such agents which are compatible with the skin and can be readily applied to the skin by standard means. Components of such carriers include, but are not limited to, one or more of water, glycerol, alcohol, propylene glycol, fatty alcohols, triglycerides, fatty acid esters, and mineral oils. Dermatologically acceptable carriers may be in the form of lotions, creams, balms, gels, mousses, aqueous liquids of varying viscosity, waxed based sticks, aerosols, alcohol sticks and the like. Dermatologically acceptable carriers may include one or more emollients, emulsifiers, surfactants, waxes, thickeners, film formers, preservatives and perfumes. Such agents are well known in the art.

In one or more embodiments, the CBD-based composition includes a liquid wax. In some embodiments, a liquid wax may be used in combination with a solid wax. Jojoba oil and oleic acid are examples of a liquid wax. In an exemplary embodiment, the liquid wax is jojoba oil (e.g., simmondsia chinensis).

Dosage forms may contain other pharmaceutically acceptable excipients for modifying conditions such as pH, osmolarity, taste, viscosity, sterility, lipophilicity, solubility etc. The choice of diluents, carriers or excipients typically depends on the desired dosage form.

Suitable dosage forms include, but are not limited to, creams, lotions, aerosols, emulsions, ointments, balms, an oleaginous composition, gel and the alike.

The sunscreen product may contain CBD in any amount that is effective in protecting the skin from UV radiation when applied for example to the surface of the skin as a thin film, i.e., about 10-15 pm in thickness. The sunscreen formulation is thus intended to act as a filter to diminish the penetration of UV radiation to the cells of the epidermis.

In one or more embodiments, the CBD is in an amount (w/w) of at least about 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% or 10% of the sunscreen composition. For example, the CBD is in an amount (w/w) of at least about 10%, at least about 20%, at least about 30%, at least about 40%, or at least about 50% of the sunscreen composition. In an exemplary embodiment, the amount of CBD is between about 0.1% and about 20%, about 0.5% and about 15%, about 0.5% and up to about 10%, between about 0.5% and about 5%, or between about 1% and about 8% of the sunscreen composition Each possibility represents a separate embodiment of the invention.

The sunscreen composition of the invention may comprise, in addition to CBD, a further sunscreen agent which optionally acts synergistically in protecting against the damaging effect of UV radiation. The additional sunscreen agent may be any sunscreen agent. The additional sunscreen agent may be an organic sunscreen agent or may be an inorganic sunscreen agent. Organic -based sunscreens may include, without limitation, paraaminobenzoic acid (PABA), PABA esters (glyceryl PABA), amyldimethyl PABA and octyldimethyl PABA), benzophenones (oxybenzone and sulisobenzone), cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (homomethyl salicylate), antbranilates such as menthyl anthranilate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5-sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4- isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, and 2-ethyl-2-cyano-3,3'- diphenyl acrylate. Each possibility represents a separate embodiment of the invention.

An inorganic sunscreen agent may include, without limitation titanium oxide and zinc oxide.

The CBD-based sunscreen composition of the invention may include less than 20%, 10%, 5%, or 1% of an additional sunscreen agent. The CBD-based sunscreen composition of the invention may be substantially free, essentially free or free of an additional sunscreen agent. The additional sunscreen agent may be any sunscreen agent. In one or more embodiments, the CBD-based sunscreen composition of the invention may be substantially free, essentially free or free of an additional organic sunscreen agent (i.e., an organic sunscreen agent other than CBD). In one or more embodiments, the CBD-based sunscreen composition of the invention may be substantially free, essentially free or free of an inorganic sunscreen agent. In one or more embodiments, the CBD-based sunscreen composition of the invention may be substantially free, essentially free or free of one or more of an organic-based sunscreens/agents selected from paraaminobenzoic acid (PABA), PABA esters (glyceryl PABA), amyldimethyl PABA and octyldimethyl PABA), benzophenones (oxybenzone and sulisobenzone), cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (homomethyl salicylate), antbranilates such as menthyl anthranilate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5- sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, and 2-ethyl-2-cyano-3,3'-diphenyl acrylate. Each possibility represents a separate embodiment of the invention. In one or more embodiments, the CBD-based sunscreen composition of the invention may be substantially free, essentially free or free of titanium oxide and/or zinc oxide. Each possibility represents a separate embodiment of the invention.

In one or more embodiments, the CBD-based sunscreen composition of the invention may be substantially free, essentially free or free of one or more of an active therapeutic agent selected from the group consisting of: an antibiotic compound, an antiseptic, an antifungal compound, an anti-acne agent, a soothing compound, smoothing compound, a moisturizing compound, steroids, an analgesic compound, and an anti-viral compound. Each possibility represents a separate embodiment of the invention.

In one or more embodiments, the CBD-based sunscreen composition of the invention may include one or more of an agent selected from the group consisting of: an antibiotic compound, an antiseptic, an antifungal compound, an anti-acne agent, a soothing compound, smoothing compound, a moisturizing compound, steroids, an analgesic compound, and an anti-viral compound. Each possibility represents a separate embodiment of the invention.

In one or more embodiments, the CBD-based sunscreen composition of the invention is substantially free, essentially free or free of one of more of a synthetic fragrance, parabens, a formaldehyde, sodium lauryl sulfate, sodium laureth sulfate, diethanolamine (DEA), silicons, phthalates, alcohols, an animal-derived ingredient, petroleum, a GMO (genetically modified organism), artificial coloring.

The dosing schedule of the compositions of the present invention can vary according to the particular application and the potency of the active ingredients. Determination of the proper dosage is within the skill of the art. For convenience, a single daily dose may be used. Alternatively, the total daily dosage may be divided and administered in portions during the day such as twice daily, thrice daily and the like. Biweekly, weekly, bimonthly and monthly administration are also contemplated.

According to some embodiments, the composition consists essentially of CBD or a derivative thereof and a dermatologically acceptable excipient or carrier. In one or more embodiments, the CBD-based composition includes a CBD and one or more of a liquid wax. Jojoba oil and oleic acid are non-limiting examples of a liquid wax. In one or more embodiments, the CBD-based composition includes one or more of a solid wax. The term "solid wax" includes“semi-solid waxy substance” or“solid waxy substance” and refers to any hydrophobic material which may be solid or semi-solid at room temperature or at body temperature. The term encompasses fatty alcohols, fatty acids and waxes which are solid or semi-solid at room temperature.

In one or more embodiments, the CBD-based composition includes one or more of a hydrophobic solvent. The hydrophobic solvent may be utilized to solubilize the CBD. In one or more embodiments, the hydrophobic solvent is an oil. Suitable oils include, without limitation a mineral oil, a hydrocarbon oil, an ester oil, an ester of a dicarboxylic acid, a triglyceride oil, an oil of plant origin, an oil from animal origin, an unsaturated or polyunsaturated oil, a diglyceride, a PPG alkyl ether, an essential oil, a silicone oil, liquid paraffin, an isoparaffin, a polyalphaolefin, a polyolefin, polyisobutylene, a synthetic isoalkane, isohexadecane, isododecane, alkyl benzoate, alkyl octanoate, C12-C15 alkyl benzoate, C12-C15 alkyl octanoate, arachidyl behenate, arachidyl propionate, benzyl laurate, benzyl myristate, benzyl palmitate, bis (octyldodecyl stearoyl) dimer dilinoleate, butyl myristate, butyl stearate, cetearyl ethylhexanoate, cetearyl isononanoate, cetyl acetate, cetyl ethylhexanoate, cetyl lactate, cetyl myristate, cetyl octanoate, cetyl palmitate, cetyl ricinoleate, decyl oleate, diethyleneglycol diethylhexanoate, diethyleneglycol dioctanoate, diethyleneglycol diisononanoate, diethyleneglycol diisononanoate, diethylhexanoate, diethylhexyl adipate, diethylhexyl malate, diethylhexyl succinate, diisopropyl adipate, diisopropyl dimerate, diisopropyl sebacate, diisosteary dimer dilinoleate, diisostearyl fumerate, dioctyl malate, dioctyl sebacate, dodecyl oleate, ethylhexyl palmitate, ester derivatives of lanolic acid, ethylhexyl cocoate, ethylhexyl ethylhexanoate, ethylhexyl hydroxystarate, ethylhexyl isononanoate, ethylhexyl palmytate, ethylhexyl pelargonate, ethylhexyl stearate, hexadecyl stearate, hexyl laurate, isoamyl laurate, isocetyl behenate, isocetyl lanolate, isocetyl palmitate, isocetyl stearate, isocetyl salicylate, isocetyl stearate, isocetyl stearoyl stearate, isocetearyl octanoate, isodecyl ethylhexanoate, isodecyl isononanoate, isodecyl oleate, isononyl isononanoate, isodecyl oleate, isohexyl decanoate, isononyl octanoate, isopropyl isostearate, isopropyl lanolate, isopropyl laurate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isostearyl behenate, isosteary citrate, isostearyl erucate, isostearyl glycolate, isostearyl isononanoate, isostearyl isostearate, isostearyl lactate, isostearyl linoleate, isostearyl linolenate, isostearyl malate, isostearyl neopentanoate, isostearyl palmitate, isosteary salicylate, isosteary tartarate, isotridecyl isononanoate, isotridecyl isononanoate, lauryl lactate, medium chain triglycerides, myristyl lactate, myristyl myristate, myristyl neopentanoate, myristyl propionate, octyldodecyl myristate, neopentylglycol dicaprate, octyl dodecanol, octyl stearate, octyl palmitate, octyldodecyl behenate, octyldodecyl hydroxystearate, octyldodecyl myristate, octyldodecyl stearoyl stearate, oleyl erucate, oleyl lactate, oleyl oleate, petrolatum, propyl myristate, propylene glycol myristyl ether acetate, propylene glycol dicaprate, propylene glycol dicaprylate, maleated soybean oil, stearyl caprate, stearyl heptanoate, stearyl propionate, tocopheryl acetate, tocopheryl linoleate, glyceryl oleate, tridecyl ethylhexanoate, tridecyl isononanoate, triisocetyl citrate, an alexandria laurel tree oil, an avocado oil, an apricot stone oil, a barley oil, a borage seed oil, a calendula oil, a canelle nut tree oil, a canola oil, caprylic/capric triglycerides, a castor oil, a coconut oil, a com oil, a cotton oil, a cottonseed oil, an evening primrose oil, a flaxseed oil, a groundnut oil, a hazelnut oil, glycereth triacetate, glycerol triheptanoate, glyceryl trioctanoate, glyceryl triundecanoate, a hempseed oil, a jojoba oil, a lucerne oil, a maize germ oil, a marrow oil, a millet oil, a neopentylglycol dicaprylate/dicaprate, an olive oil, a palm oil, a passionflower oil, pentaerythrityl tetrastearate, a poppy oil, propylene glycol ricinoleate, a rapeseed oil, a rye oil, a safflower oil, a sesame oil, a shea butter, a soya oil, a soybean oil, a sweet almond oil, a sunflower oil, a sysymbrium oil, a syzigium aromaticum oil, a tea tree oil, a walnut oil, wheat germ glycerides, a wheat germ oil, a PPG- 2 butyl ether, a PPG-4 butyl ether, a PPG-5 butyl ether, a PPG-9 butyl ether, a PPG- 12 butyl ether, a PPG- 14 butyl ether, a PPG- 15 butyl ether, a PPG- 15 stearyl ether, a PPG- 16 butyl ether, a PPG- 17 butyl ether, a PPG- 18 butyl ether, a PPG-20 butyl ether, a PPG-22 butyl ether, a PPG-24 butyl ether, a PPG-26 butyl ether, a PPG-30 butyl ether, a PPG-33 butyl ether, a PPG-40 butyl ether, a PPG-52 butyl ether, a PPG-53 butyl ether, a PPG- 10 cetyl ether, a PPG-28 cetyl ether, a PPG-30 cetyl ether, a PPG-50 cetyl ether, a PPG-30 isocetyl ether, a PPG-4 lauryl ether, a PPG-7 lauryl ether, a PPG-2 methyl ether, a PPG-3 methyl ether, a PPG-3 myristyl ether, a PPG-4 myristyl ether, a PPG- 10 oleyl ether, a PPG- 20 oleyl ether, a PPG-23 oleyl ether, a PPG-30 oleyl ether, a PPG-37 oleyl ether, a PPG- 40 butyl ether, a PPG-50 oleyl ether, a PPG-l 1 stearyl ether, a herring oil, a cod-liver oil, a salmon oil, a cyclomethicone, a dimethyl polysiloxane, a dimethicone, an epoxy- modified silicone oil, a fatty acid-modified silicone oil, a fluoro group-modified silicone oil, a methylphenylpolysiloxane, phenyl trimethicone, a polyether group-modified silicone oil, and a mixture of any two or more thereof.

Depending on the dosage form, the CBD compositions may include one or more of a liquid wax and/or a solid wax. Optionally, the CBD compositions include jojoba oil.

An exemplary lotion composition may include CBD, and one or more of: a candelilla wax, a shea butter, coconut oil, and jojoba oil. An exemplary oil composition includes CBD, Jojoba oil, and magnesium. An exemplary cream composition includes CBD, candelilla wax, shea butter, jojoba oil, and shea butter. An exemplary balm composition includes CBD, candelilla wax, cocoa butter, shea butter, and jojoba oil.

An exemplary skin protective lotion may include:

up to about 15% by weight of the composition of CBD;

up to about 20% by weigh of the composition of a solid wax (e.g., candelilla wax);

up to about 30% by weigh of the composition of a hydrophobic agent (e.g., shea butter and coconut oil); and

up to about 30% by weight of the composition of liquid wax (e.g., jojoba oil).

An exemplary skin protective oil may include:

up to about 15% by weight of the composition of CBD; and

up to about 95% (w/w) of Jojoba oil. Optionally, an addition of magnesium may be included.

An exemplary skin protective cream may include:

up to about 15% by weight of the composition of CBD; up to about 5% (w/w) of candelilla wax;

up to about 5% (w/w) of shea butter;

up to about 10 % (w/w) of jojoba oil; and

up to about 5% (w/w) of shea butter.

An exemplary skin protective balm may include:

up to about 15% by weight of the composition of CBD;

up to about 5% (w/w) of candelilla wax

up to about 10% (w/w) of cocoa butter;

up to about 5% (w/w) of shea butter; and

up to about 10% (w/w) of Jojoba oil.

According to yet further embodiments, the composition consists of CBD or a derivative thereof and a dermatologically acceptable excipient or carrier

The following examples are presented in order to more fully illustrate some embodiments of the invention. They should, in no way be construed, however, as limiting the broad scope of the invention. One skilled in the art can readily devise many variations and modifications of the principles disclosed herein without departing from the scope of the invention.

EXAMPLES

Example 1: CBD attenuates UVB-induced apoptosis in a skin epidermis.

To investigate the safety and efficacy of CBD, an ex-vivo human skin model was employed. Skin was sectioned, using a mechanical skin press, to 0.8 X 0.8 cm² pieces. The skin explants were maintained in an air/liquid interface; wherein the dermal side submerge in medium.

The human skin explants were treated with increasing concentrations of CBD or with a corresponding vehicle. Epidermis viability was measured by an MTT assay. FIG. 1 shows that topical application of CBD was well tolerated by the human skin explants and did not compromise the skin's viability up to the maximal CBD concentration tested, as measured by the MTT assay. UV radiation effect was then assessed. Skins were exposed to UVB radiation (350 mJ/cm²). Following 24 hours of exposure to the UVB radiation, apoptosis levels were measured and determined by caspase 3 activity assay. Ultrasol® (Dr. Fisher, SPF 30) served as positive control (PC).

As can be seen in FIG. 2, CBD at all concentrations tested attenuated UVB-induced apoptosis in the epidermis, one of the hallmark pathways activated by solar radiation. Ultrasol® formulation (SPF 30) was served as a positive control (PC). Optionally, CBD's action was associated with its potent antioxidant capacity (25.298 ± 1,520 m M Trolox equivalent 100 g) determined by the DPPH method. Optionally, and/or additionally CBD's action was due to a physical blockage effect of radiation (calculated SPF value of ~0.5).

Example 2: CBD-based skin protective cosmetic formulations

Typically, topical compositions for protecting skin against the adverse effects of the environment, including ultraviolet radiation, comprise of active ingredients distributed in emulsion between water and oil phases. The consistency and stability of the target products are due to some enhancers (e.g., emulsifiers, stabilizers, etc.), but recent studies have shown that some of the most often used ones are harmful to human health. For this reason, natural products are becoming an increasingly reliable source of safe ingredients for cosmetics purposes.

Exemplary topical CBD-based skin protective compositions may include between 0.5% and 10% (w/w) CBD and a liquid wax (e.g., jojoba oil) i) Exemplary skin protective lotions (50 g base formulation):

CBD - 0.5% (w/w) to 10% (w/w)

Candelilla wax - 5% (w/w) to 15% (w/w)

Shea butter - 0.5% (w/w) to 1.5% (w/w)

Coconut oil - 5% (w/w) to 15% (w/w)

Jojoba oil 15% (w/w) to 30% (w/w). ii) Exemplary skin protective oils (50 g base formulation):

CBD - 0.5% (w/w) to 10% (w/w)

Jojoba oil - 85% (w/w) to 98% (w/w)

Up to 1 g elemental magnesium iii) Exemplary skin protective creams (50 g base formulation):

CBD - 0.5% (w/w) to 10% (w/w)

Candelilla wax - 1 % (w/w)

Shea butter - 3% (w/w) to 4% (w/w)

Jojoba oil - 2% (w/w) to 8% (w/w)

Shea butter - 1 % (w/w)

(iv) Exemplary skin protective balms (50 g base formulation):

CBD - 0.5% (w/w) to 10% (w/w)

Candelilla wax - 0.5% (w/w) to 1.5% (w/w)

Cocoa butter (Coconut oil) - 1.7% to 6% (w/w)

Shea butter - 0 to 4% (w/w) (e.g., 1.7)

Jojoba oil - 1.7% to 8% (w/w) (e.g., 3).

Addition of supplements may optionally include essential oils (e.g., up to 20 drops of essential oils per 50 g of cream, balm, or lotion), Vitamin E oil (e.g., 0.5 - 1% per 50 g skin-care product). In one or more embodiments, the addition of vitamin E may be significant due to its antioxidant properties that benefit the skin, particularly aging and scarred skin, by neutralizing the oxidant effects of free radicals, and the general damage - wrinkles, fine lines and dryness - that free radicals can do.

It should be noted that the term“substantially free of’ an ingredient as provided throughout the specification is intended to mean that the composition comprises less than about 0.5% by weight, less than about 0.4% by weight, less than about 0.3% by weight, less than about 0.2% by weight, or less than about 0.1% by weight, of an ingredient unless specifically indicated otherwise. In some embodiments, a composition“substantially free of’ an ingredient comprises less than 0.5% by weight, less than 0.4% by weight, less than 0.3% by weight, less than 0.2% by weight, or less than 0.1% by weight of the ingredient.

As used herein, the term“essentially free of’ an ingredient as provided throughout the specification is intended to mean that the composition comprises less than about 0.05% by weight, less than about 0.01% by weight, or less than about 0.001% by weight of the ingredient, unless specifically indicated otherwise. In some embodiments, a composition “essentially free of’ an ingredient comprises less than 0.05% by weight, less than 0.01% by weight, or less than 0.001% by weight of the ingredient.

As used herein, the term“free of’ an ingredient as provided throughout the specification is intended to mean that the composition does not comprise the ingredient or comprises a trace amount of the ingredient, unless specifically indicated otherwise.

Each of the following terms: 'includes', 'including', 'has', 'having', 'comprises', and 'comprising', and, their linguistic, as used herein, means 'including, but not limited to', and is to be taken as specifying the stated component(s), feature(s), characteristic(s), parameter(s), integer(s), or step(s), and does not preclude addition of one or more additional component(s), feature(s), characteristic(s), parameter(s), integer(s), step(s), or groups thereof. Each of these terms is considered equivalent in meaning to the phrase 'consisting essentially of.

Each of the phrases 'consisting of and 'consists of, as used herein, means 'including and limited to'.

The term 'method', as used herein, refers to steps, procedures, manners, means, or/and techniques, for accomplishing a given task including, but not limited to, those steps, procedures, manners, means, or/and techniques, either known to, or readily developed from known steps, procedures, manners, means, or/and techniques, by practitioners in the relevant field(s) of the disclosed invention.

Throughout this disclosure, a numerical value of a parameter, feature, characteristic, object, or dimension, may be stated or described in terms of a numerical range format. Such a numerical range format, as used herein, illustrates implementation of some exemplary embodiments of the invention, and does not inflexibly limit the scope of the exemplary embodiments of the invention. Accordingly, a stated or described numerical range also refers to, and encompasses, all possible sub-ranges and individual numerical values (where a numerical value may be expressed as a whole, integral, or fractional number) within that stated or described numerical range. For example, a stated or described numerical range 'from 1 to 6' also refers to, and encompasses, all possible sub-ranges, such as 'from 1 to 3', 'from 1 to 4', 'from 1 to 5', 'from 2 to 4', 'from 2 to 6', 'from 3 to 6', etc., and individual numerical values, such as T, Ί.3', '2', '2.8', '3', '3.5', '4', '4.6', '5', '5.2', and '6', within the stated or described numerical range of 'from 1 to 6'. This applies regardless of the numerical breadth, extent, or size, of the stated or described numerical range.

Moreover, for stating or describing a numerical range, the phrase 'in a range of between about a first numerical value and about a second numerical value', is considered equivalent to, and meaning the same as, the phrase 'in a range of from about a first numerical value to about a second numerical value', and, thus, the two equivalently meaning phrases may be used interchangeably.

The term 'about', is some embodiments, refers to ±30 % of the stated numerical value. In further embodiments, the term refers to ±20 % of the stated numerical value. In yet further embodiments, the term refers to ±10 % of the stated numerical value.

It is to be fully understood that certain aspects, characteristics, and features, of the invention, which are, for clarity, illustratively described and presented in the context or format of a plurality of separate embodiments, may also be illustratively described and presented in any suitable combination or sub-combination in the context or format of a single embodiment. Conversely, various aspects, characteristics, and features, of the invention which are illustratively described and presented in combination or sub combination in the context or format of a single embodiment, may also be illustratively described and presented in the context or format of a plurality of separate embodiments.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications, and variations that fall within the spirit and broad scope of the appended claims.

All publications, patents, and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

Claims

1. A method of protecting the skin of a subject in need thereof from damages associated with exposure of the subject to ultraviolet (UV) radiation, the method comprising topically administering to the subject a composition comprising a cannabidiol (CBD) and a pharmaceutically acceptable carrier or excipient, wherein the cannabidiol (CBD) is provided in the composition in an amount that effectively prevents or attenuates UV radiation-associated skin cells' apoptosis.

2. The method according to claim 1 , wherein the composition is substantially free of an organic sunscreen agent other than CBD.

3. The method according to claim 2, wherein the organic sunscreen agent is selected from the group consisting of paraaminobenzoic acid (PABA), PABA esters (glyceryl PABA), amyldimethyl PABA and octyldimethyl PABA, benzophenones (oxybenzone and sulisobenzone), cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (homomethyl salicylate), anthranilates such as menthyl anthranilate, 2-ethylhexyl-2- cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5-sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, 2-ethyl-2-cyano-3,3'-diphenyl acrylate and a combination thereof.

4. The method according to claim 1 , wherein the composition is substantially free of an inorganic sunscreen agent sunscreen.

5. The method according to claim 4, wherein the inorganic sunscreen agent is zinc oxide and/or titanium oxide.

6. The method according to any one of claims 1-5, wherein the CBD is provided in an amount within the range of about 0.5% and about 10% by weight of the composition.

7. The method according to any one of claims 1-6, wherein the CBD composition includes a liquid wax.

8. The method according to claim 7, wherein the liquid wax is jojoba oil.

9. The method according to any one of claims 1-8, wherein the CBD is capable of inhibiting caspase 4 expression in dermal or epidermal cells.

10. The method according to any one of claims 1-10, wherein the CBD provided in an amount of at least about 6 x 10 ³ pg/crrr and wherein said amount of CBD attenuates apoptosis at least about 2 times higher as compared to a control subject.

11. The method according to any one of claims 1-10, wherein the CBD is provided within the composition as a natural cannabis plant extract.

12. The method according to claim 12, wherein the CBD is present in the cannabis plant extract in an amount of at least about 90% (w/w).

13. The method according to any one of claims 1-12, wherein the CBD is present in the composition as a synthetic compound.

14. The method according to any one of claims 1-13, wherein the CBD is a derivative of CBD.

15. A method of preventing or attenuating UV radiation-induced apoptosis in a cell, the method comprising applying onto or incubating the cells with a composition comprising an effective amount of cannabidiol (CBD) and an acceptable carrier.

16. The method according to claim 15, wherein the cell is a dermal cell and/or an epidermal cell.

17. The method according to claim 15 or 16, wherein the CBD provided in an amount of at least about 6 x 10 ³ pg/cm² and wherein said amount of CBD attenuates apoptosis at least about 2 times higher as compared to a control subject.

18. The method according to any one of claims 15-17, wherein the CBD is capable of inhibiting caspase 4 expression in dermal or epidermal cells.

19. The method according to any one of claims 15-18, wherein the CBD is present as a highly purified extract of cannabis which comprises at least about 90% (w/w) CBD of the total extract.

20. The method according to any one of claims 15-19, wherein the CBD is present in the composition as a synthetic compound.

21. The method according to any one of claims 15-20, wherein the composition is substantially free of a sunscreen agent other than CBD.

22. The method according to any one of claims 15-21, wherein the CBD is a derivative of CBD.

23. A sunscreen composition comprising a cannabidiol (CBD); and a pharmaceutically acceptable carrier or excipient, wherein the CBD is provided in the composition in an amount that effectively prevents or attenuates UV radiation-associated skin damage.

24. The sunscreen composition according to claim 23, wherein the composition is substantially free of an organic sunscreen agent other than CBD.

25. The sunscreen composition according to claim 23 or 24, wherein the composition is substantially free of an inorganic sunscreen agent.

26. The sunscreen composition according to claim 25, wherein the inorganic sunscreen agent is zinc oxide and/or titanium oxide.

27. The sunscreen composition according to claim 24, wherein the organic sunscreen agent is selected from the group consisting of paraaminobenzoic acid (PABA), PABA esters (glyceryl PABA), amyldimethyl PABA and octyldimethyl PABA, benzophenones (oxybenzone and sulisobenzone), cinnamates (octylmethoxy cinnamate and cinoxate), salicylates (homomethyl salicylate), anthranilates such as menthyl anthranilate, 2- ethylhexyl-2-cyano-3, 3-diphenyl acrylate, 2-phenyl benzimidazole-5 -sulfonic acid, digalloyl trioleate, 3-(4-methyl benzylidene) camphor, 4-isopropyl dibenzoyl methane, butyl methoxy dibenzoyl methane, 2-ethyl-2-cyano-3,3'-diphenyl acrylate and a combination thereof.

28. The sunscreen composition according to any one of claims 23-27, wherein the CBD is provided in an amount of about 0.5% to about 10% by weight of the composition.

29. The sunscreen composition according to any one of claims 23-28, wherein the CBD is capable of attenuating UV-induced skin cells apoptosis.

30. The sunscreen composition according to claim 29, wherein the CBD is capable of inhibiting caspase 4 expression in dermal or epidermal cells.

31. The sunscreen composition according to any one of claims 23-30, wherein the CBD composition further comprises a liquid wax.

32. The sunscreen composition according to claim 31, wherein the liquid wax is jojoba oil.

33. The sunscreen composition according to any one of claims 23-32, wherein the CBD is provided within the composition as a natural cannabis plant extract.

34. The sunscreen composition according to claim 33, wherein the CBD is present in the cannabis plant extract in an amount of at least about 90% (w/w).

35. The sunscreen composition according to any one of claims 23-34, wherein the CBD is in a crystalline form of CBD.

36. The sunscreen composition according to any one of claims 23-35, wherein the CBD is present in the composition as a synthetic compound.

37. The sunscreen composition according to any one of claims 23-36, wherein the CBD is a derivative of CBD.