Analgesic and Anti-Inflammatory Effects of 1% Tropical Cannabidiol Gel in Animal Models

pubmed logo

“Introduction: Cannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is an interesting candidate for studying its anti-inflammatory effects, especially in the pre-clinical and animal models. Its anti-inflammatory effects, such as reduction of edema and arthritis, have been demonstrated in animal models. However, topical CBD administration requires further evaluation of CBD dosage and efficacy in animal models and clinical settings. 

Methods: This in vivo study investigated the anti-inflammatory effects of topical CBD administration in an animal model. Scientific experiments, including the formalin test, writhing test, carrageenan-induced edema, histopathological examination, and detection of various proinflammatory mediators, were performed. 

Results: The anti-inflammatory effects in vivo after inflammation induction, represented by decreased times of paw licking, degree of paw edema, and decreased writhing response, showed that 1% of tropical CBD use had significantly comparable or better anti-inflammatory effects when compared with tropical diclofenac, an anti-inflammatory agent. Moreover, the anti-inflammatory effects were significant compared with the placebo. In addition, the histopathological examination showed that topical CBD drastically reduced leukocyte infiltration and the degree of inflammation. This study also showed that the levels of various proinflammatory mediators in the plasma of mice treated with topical CBD did not differ from those treated with diclofenac. 

Conclusions: The topical administration of 1% CBD gel is a potentially effective candidate for an anti-inflammatory agent. Candidate for an anti-inflammatory agent.”

Therapeutic Potential of Minor Cannabinoids in Dermatological Diseases-A Synthetic Review

pubmed logo

“Dermatological diseases pose a significant burden on the quality of life of individuals and can be challenging to treat effectively. In this aspect, cannabinoids are gaining increasing importance due to their therapeutic potential in various disease entities including skin diseases. In this synthetic review, we comprehensively analyzed the existing literature in the field of potential dermatological applications of a lesser-known subgroup of cannabinoids, the so-called minor cannabinoids, such as cannabidivarin (CBDV), cannabidiforol (CBDP), cannabichromene (CBC), tetrahydrocannabivarin (THCV), cannabigerolic acid (CBGA), cannabigerol (CBG), cannabielsoin (CBE), cannabimovone (CBM) or cannabinol (CBN), while drawing attention to their unique pharmacological properties. We systematically searched the available databases for relevant studies and analyzed the data to provide an overview of current thematic knowledge. We looked through the full-text, bibliographic and factographic databases, especially Scopus, Web of Science, PubMed, Polish Scientific Journals Database, and selected the most relevant papers. Our review highlights that minor cannabinoids exhibit diverse pharmacological activities, including anti-inflammatory, analgesic, antimicrobial, and anti-itch properties. Several studies have reported their efficacy in mitigating symptoms associated with dermatological diseases such as psoriasis, eczema, acne, and pruritus. Furthermore, minor cannabinoids have shown potential in regulating sebum production, a crucial factor in acne pathogenesis. The findings of this review suggest that minor cannabinoids hold therapeutic promise in the management of dermatological diseases. Further preclinical and clinical investigations are warranted to elucidate their mechanisms of action, determine optimal dosage regimens, and assess long-term safety profiles. Incorporating minor cannabinoids into dermatological therapies could potentially offer novel treatment options of patients and improve their overall well-being.”

Cannabidiol and Cannabigerol Modify the Composition and Physicochemical Properties of Keratinocyte Membranes Exposed to UVA

pubmed logo

“The action of UVA radiation (both that derived from solar radiation and that used in the treatment of skin diseases) modifies the function and composition of keratinocyte membranes. Therefore, this study aimed to assess the effects of phytocannabinoids (CBD and CBG), used singly and in combination, on the contents of phospholipids, ceramides, lipid rafts and sialic acid in keratinocyte membranes exposed to UVA radiation, together with their structure and functionality. The phytocannabinoids, especially in combination (CBD+CBG), partially prevented increased levels of phosphatidylinositols and sialic acid from occurring and sphingomyelinase activity after the UVA exposure of keratinocytes. This was accompanied by a reduction in the formation of lipid rafts and malondialdehyde, which correlated with the parameters responsible for the integrity and functionality of the keratinocyte membrane (membrane fluidity and permeability and the activity of transmembrane transporters), compared to UVA-irradiated cells. This suggests that the simultaneous use of two phytocannabinoids may have a protective effect on healthy cells, without significantly reducing the therapeutic effect of UV radiation used to treat skin diseases such as psoriasis.”

“Since UVA radiation modifies the composition, structure and functionality of the lipid bilayer of keratinocyte membranes, the use of natural compounds, especially lipophilic compounds such as phytocannabinoids, is important for maintaining the proper condition of the skin and, consequently, for the proper functioning of the skin over the entire human body. “

Rare Phytocannabinoids Exert Anti-Inflammatory Effects on Human Keratinocytes via the Endocannabinoid System and MAPK Signaling Pathway


“Increasing evidence supports the therapeutic potential of rare cannabis-derived phytocannabinoids (pCBs) in skin disorders such as atopic dermatitis, psoriasis, pruritus, and acne. However, the molecular mechanisms of the biological action of these pCBs remain poorly investigated.

In this study, an experimental model of inflamed human keratinocytes (HaCaT cells) was set up by using lipopolysaccharide (LPS) in order to investigate the anti-inflammatory effects of the rare pCBs cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) and cannabigerolic acid (CBGA). To this aim, pro-inflammatory interleukins (IL)-1β, IL-8, IL-12, IL-31, tumor necrosis factor (TNF-β) and anti-inflammatory IL-10 levels were measured through ELISA quantification. In addition, IL-12 and IL-31 levels were measured after treatment of HaCaT cells with THCV and CBGA in the presence of selected modulators of endocannabinoid (eCB) signaling. In the latter cells, the activation of 17 distinct proteins along the mitogen-activated protein kinase (MAPK) pathway was also investigated via Human Phosphorylation Array.

Our results demonstrate that rare pCBs significantly blocked inflammation by reducing the release of all pro-inflammatory ILs tested, except for TNF-β. Moreover, the reduction of IL-31 expression by THCV and CBGA was significantly reverted by blocking the eCB-binding TRPV1 receptor and by inhibiting the eCB-hydrolase MAGL. Remarkably, THCV and CBGA modulated the expression of the phosphorylated forms (and hence of the activity) of the MAPK-related proteins GSK3β, MEK1, MKK6 and CREB also by engaging eCB hydrolases MAGL and FAAH.

Taken together, the ability of rare pCBs to exert an anti-inflammatory effect in human keratinocytes through modifications of eCB and MAPK signaling opens new perspectives for the treatment of inflammation-related skin pathologies.”

“Overall, this proof of concept, which shows that in inflamed human keratinocytes, rare pCBs can indeed interact with specific eCB system elements, opens new perspectives for possible treatments of inflammation-related skin diseases. Incidentally, such interactions between pCBs and eCB system seems to hold therapeutic potential well beyond the skin, such as possible treatments reported for autism spectrum disorders and cancer”

“Effects of Rare Phytocannabinoids on the Endocannabinoid System of Human Keratinocytes”

Phytocannabinoids in the Pharmacotherapy of Psoriasis


“Phytocannabinoids are naturally occurring compounds, the main source of which is Cannabis sativa L. Through direct action or interaction with G protein-coupled receptors, they affect ROS and pro-inflammatory cytokines levels and modify the effectiveness of transcription factor responsible for the biosynthesis of antioxidants which lead to oxidative stress and its consequences. Due to the modification of the redox balance and inflammation, phytocannabinoids are used in the treatment of various diseases, including autoimmune dermatoses, such as atopic dermatitis and psoriasis. Psoriasis is one of the most common dermatoses, and one of unknown etiology. A disturbed redox balance with a shift towards the oxidation leads to oxidative stress, resulting in oxidative modifications, mainly of lipids and proteins, and prolonged activation of immune cells and increased generation of pro-inflammatory cytokines, resulting in chronic inflammation. Given the biological activity of phytocannabinoids, they have become the focus of research as components of pharmacotherapy for psoriasis. Beneficial effects were shown by various representatives of phytocannabinoids, but the effect of cannabidiol (CBD) on skin cells (in vitro and ex vivo) and on blood cells from patients with psoriasis vulgaris and psoriatic arthritis has been most often evaluated in recent years.”

Cannabidiol and Cannabigerol Exert Antimicrobial Activity without Compromising Skin Microbiota


“Cannabidiol (CBD) and cannabigerol (CBG) are two pharmacologically active phytocannabinoids of Cannabis sativa L. Their antimicrobial activity needs further elucidation, particularly for CBG, as reports on this cannabinoid are scarce. We investigated CBD and CBG’s antimicrobial potential, including their ability to inhibit the formation and cause the removal of biofilms.

Our results demonstrate that both molecules present activity against planktonic bacteria and biofilms, with both cannabinoids removing mature biofilms at concentrations below the determined minimum inhibitory concentrations. We report for the first time minimum inhibitory and lethal concentrations for Pseudomonas aeruginosa and Escherichia coli (ranging from 400 to 3180 µM), as well as the ability of cannabinoids to inhibit Staphylococci adhesion to keratinocytes, with CBG demonstrating higher activity than CBD. The value of these molecules as preservative ingredients for cosmetics was also assayed, with CBG meeting the USP 51 challenge test criteria for antimicrobial effectiveness. Further, the exact formulation showed no negative impact on skin microbiota.

Our results suggest that phytocannabinoids can be promising topical antimicrobial agents when searching for novel therapeutic candidates for different skin conditions. Additional research is needed to clarify phytocannabinoids’ mechanisms of action, aiming to develop practical applications in dermatological use.”

“This report compares CBD and CBG’s antimicrobial effectiveness and further cements phytocannabinoids’ potential to be used as antimicrobial agents. Both molecules’ antimicrobial capacity strongly depends on the target microorganism, namely whether it is Gram-negative or Gram-positive. Nonetheless, we were able to determine MICs for all tested strains, including S. pyogenesE. coli, and P. aeruginosa. It is of note that CBG revealed a stronger antimicrobial effect than CBD, particularly in the challenge test and in the antibiofilm assay. Further studies are needed to understand these discrepancies, as they may be connected to structural differences, receptor-binding affinity, or another mechanism other than a receptor-mediated one. Since no significant impact on the skin microbiota was observed and given its current widespread use, both CBD and CBG might be considered safe. Thus, we can assume that the development of topical formulations with active concentrations of CBG and/or CBD might represent a promising approach to tackle skin conditions where microorganisms and inflammation play a fundamental role, including psoriasis, atopic dermatitis, and acne.”

The Modulation of Blue-Light-Induced Inflammation, Intracellular Lipid Secretion, and Oxidative Stress in Sebocytes with Cannabidiol

“Light-induced skin damage leads to cellular or molecular dysfunction, thus potentially causing different skin issues (e.g., skin aging, seborrheic dermatitis and pigmentation). Blue light, a potent visible light that was previously adopted for promoting skin regeneration, draws considerable concerns in the past several years due to their potential damage to the skins. In this work, we investigated the roles of blue light in skewing the functions of sebocytes – the major cells that compose the sebaceous gland – an important “active” neuro-immuno-endocrine organ in maintaining skin functions.

For therapeutically purposes, we employed cannabidiol (CBD), a clinically used non-psychotropic phytocannabinoid, to revert blue-light-induced sebocytes dysfunctions, including intracellular lipid secretion, inflammation, reactive oxygen species (ROS) secretion, and cell cycles. At the cellular level, CBD reduced the blue-light-enhanced intracellular lipid secretion, decreased inflammation, down-regulated intracellular ROS production, and restored the skewed cell cycles in the sebocytes. In the intracellular mechanism, CBD inhibited the blue-light-induced pro-apoptotic activity through rebalance BCL-2/BAX expression and down-regulated the NF-κB p65 pathway.

Collectively, this study demonstrated that CBD was a potent therapeutic agent for maintaining normal sebocytes functions, thus is a promising drug for skincare purposes, especially considering its effectiveness in restoring the twisted sebocytes behaviors.”

Medical cannabis dimethyl ether, ethanol and butane extracts inhibit the in vitro growth of bacteria and dermatophytes causing common skin diseases

Frontiers - Crunchbase Company Profile & Funding

“Cannabis preparations are gaining popularity among patients with various skin diseases. Due to the lack of scientific evidence, dermatologists remain cautious about their prescriptions. So far, only a few studies have been published about the effects of high-potency cannabis extracts on microorganisms (especially dermatophytes) causing skin problems that affect more than 25% of the worldwide population. Even though, the high-potency cannabis extracts prepared by cold extraction are mostly composed of non-psychoactive tetrahydrocannabinolic acid (THCA) and only low amount of THC, their use in topical treatment can be stigmatized. The in vitro antimicrobial and antifungal activity of two high potent cannabis strains extracted by three solvents traditionally or currently used by cannabis users (ethanol; EtOH, butane; BUT, dimethyl ether; DME) was investigated by broth dilution method. The chemical profile of cannabis was determined by high-performance liquid chromatography with ultraviolet detection and gas chromatography with mass spectrometer and flame ionization detector. The extraction methods significantly influenced chemical profile of extracts. The yield of EtOH extracts contained less cannabinoids and terpenes compared to BUT and DME ones. Most of the extracts was predominantly (>60%) composed of various cannabinoids, especially THCA. All of them demonstrated activity against 18 of the 19 microorganisms tested. The minimal inhibitory concentrations (MICs) of the extracts ranged from 4 to 256 μg/mL. In general, the bacteria were more susceptible to the extracts than dermatophytes. Due to the lower content of biologically active substances, the EtOH extracts were less effective against microorganisms. Cannabis extracts may be of value to treat dermatophytosis and other skin diseases caused by various microorganisms. Therefore, they could serve as an alternative or supportive treatment to commonly used antibiotics.”

“Our research brought new evidence that cannabis extracts may be of value to treat dermatophytosis and other skin diseases caused by various microorganisms and showed that cannabis could serve as an alternative or supportive treatment to commonly used antibiotics.”

Topical cannabidiol (CBD) in skin pathology – A comprehensive review and prospects for new therapeutic opportunities

“Humans have utilised cannabis products in various forms throughout the recorded history. To date, more than 500 biologically active components have been identified in the plants of the Cannabis genus, amongst which more than 100 were classified as phytocannabinoids (exocannabinoids).

The plant genus Cannabis is a member of the plant family Cannabaceae, and there are three primary cannabis species which vary in their biochemical constituents: Cannabis sativa, Cannabis indica and Cannabis ruderalis. There has been a growing level of interest in research on the topical usage of a cannabis-based extract as a safer and more effective alternative to the usage of topical corticosteroids in treating some dermatoses.

Together with the discovery of the cannabinoid receptors on the skin, it has been further illustrated that topical cannabis has anti-inflammatory, anti-itching, analgesics, wound healing and anti-proliferative effects on the skin.”

Cannabis sativa and Skin Health: Dissecting the Role of Phytocannabinoids

“The use of Cannabis sativa is currently recognized to ease certain types of chronic pain, reduce chemotherapy-induced nausea, and improve anxiety. Nevertheless, few studies highlighted the therapeutic potential of C. sativa extracts and related phytocannabinoids for a variety of widespread skin disorders including acne, atopic dermatitis, psoriasis, pruritus, and pain. This review summarized the current evidence on the effects of phytocannabinoids at the cutaneous level through the collection of in vitro, in vivo, and clinical studies published on PubMed, Scopus, Embase, and Web of Science until October 2020.

Phytocannabinoids have demonstrated potential anti-inflammatory, antioxidant, anti-aging, and anti-acne properties by various mechanisms involving either CB1/2-dependent and independent pathways.

Not only classical immune cells, but also several skin-specific actors, such as keratinocytes, fibroblasts, melanocytes, and sebocytes, may represent a target for phytocannabinoids. Cannabidiol, the most investigated compound, revealed photoprotective, antioxidant, and anti-inflammatory mechanisms at the cutaneous level, while the possible impact on cell differentiation, especially in the case of psoriasis, would require further investigation. Animal models and pilot clinical studies supported the application of cannabidiol in inflammatory-based skin diseases. Also, one of the most promising applications of non-psychotropic phytocannabinoids is the treatment of seborrheic disorders, especially acne. In conclusion, the incomplete knowledge of the role of the endocannabinoid system in skin disorders emerged as an important limit for pharmacological investigations. Moreover, the limited studies conducted on C. sativa extracts suggested a higher potency than single phytocannabinoids, thus stimulating new research on phytocannabinoid interaction.”