cbd salve for skin cancer

December 15, 2021 By admin Off

We feel that it is important to point out that there is also good evidence that smoking cannabis (as opposed to a topical application) significantly increases the risk of lung and head and neck cancer, whether or not it is used in combination with tobacco. Whilst there may in the future be a place for medicinal use of cannabinoids, at present the evidence very strongly suggests that in almost all cases the side effects outweigh the benefits.

Cannabinoids do bind to receptors which are present in many cells and there is some evidence in highly controlled laboratory circumstances that cannabinoids may inhibit some cancers. Sadly, there is also evidence that it may actually accelerate growth in others. There have been no useful trials in living humans and animal trials are not conclusive. The link at the end of this article gives more information and is maintained by the Uk Cancer Society so may be seen as a trusted and valid reference.

The good news is that not all skin cancers need surgery – some may be suitable for treatment with cream, especially in older patients and in many cases, the treatment is fully funded.

A patient recently asked if Cannabis oil might be used to cure a small skin cancer.

If you think you may have a skin cancer, please make an appointment – our doctors are very good at skin diagnoses and can give you proper treatment advice from leaving harmless things alone through creams to surgical removal if required.

It is important to note that some of the cancers being illustrated as treated with the oil are of a type that can spread and potentially kill the patient. We feel that using a totally untrialled medication like cannabis oil in such circumstances is very unwise.

Addendum September 2016:

A search of the internet lists many sites where people claim to have had skin cancers cured by cannabis oil. This effect may occur for one of the following reasons:

Cannabis oil is of course illegal in New Zealand so as a treatment option it is not valid in any case. Hemp oil contains cannabinoids but the concentration is much lower.

Never having been asked this before, a thorough review of the available literature was carried out, but sadly there have been absolutely no published clinical trials to date so it is impossible to recommend this treatment.

The proposed mechanisms of action of cannabis oil are plausible but unfortunately that does not make it safe or effective.

We have been asked to provide evidence to support the statement that cannabis smoking causes cancer. The spectrum of carcinogens in cannabis smoke is similar to that in tobacco smoke. It is the inhaling of burned leaves that results in tar deposition in the lungs. Cannabis smoke is generally retained in the lungs for longer than tobacco smoke which may also explain how cannabis causes chronic obstructive pulmonary disease. In a New Zealand study in 2008, it was found that cannabis smoking was associated with similar, or higher rate of lung cancer than tobacco smoking. Cannabis has also been associated with testicular cancer. Recent evidence casts doubt on the assertion that head and neck cancers are caused by cannabis smoking though it is important to note that the development of head and neck cancer is very slow and often occurs in association with other risk-factors. Some studies have shown an association and some have not. It remains our advice that the smoking of any substance is profoundly unwise and there is no reason to believe that cannabis is any safer than tobacco.

Results shown represent means ± SD. Statistical analysis was performed by ANOVA with a post hoc analysis by the Student-Neuman-Keuls test. Data in Table ​ Table1, 1 , Figure ​ Figure5a, 5 a, and Figure ​ Figure6c 6 c were analyzed by the Mann-Whitney (Wilcoxon) W test to compare medians for nonparametric data.

Quantification of apoptotic and proliferative cells in vehicle- and cannabinoid-treated skin carcinomas.

1 Project on Cellular and Molecular Biology and Gene Therapy, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain 2 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain 3 Department of Pathology, Hospital General de Móstoles, Madrid, Spain 4 Department of Chemistry, Clemson University, Clemson, South Carolina, USA.

EGF-R participates in the regulation of key epidermal functions (35–38). Moreover, we have shown that in mouse skin carcinomas EGF-R–dependent Ha- ras activation plays a pivotal role in VEGF expression and tumor angiogenesis and growth (9). Carcinoma growth arising from subcutaneous injection of tumor epidermal cells is a biphasic process. The first phase of slow growth occurs independently of EGF-R function. Later, an angiogenic switch response mediated by the EGF-R seems to be an essential requirement for complete tumor growth, involving high VEGF levels. Other members of the EGF-R family such as HER2 may also exert their relevant anticarcinogenic role via modulation of angiogenesis (39). Here we show that cannabinoid treatment impairs EGF-R function, VEGF expression, and angiogenesis in skin tumors. It is of interest that inhibition of EGF-R function also occurred upon exposure of cultured skin tumor cells to cannabinoids, indicating that the changes observed in EGF-R activity in vivo reflect a direct impact of cannabinoids on tumor cells and are not a mere consequence of decreased tumor size. Although at present we cannot establish the mechanism for the decrease of EGF-R phosphorylation in cannabinoid-treated tumors, it is tempting to speculate that cannabinoid treatment interferes with the tumor angiogenic switch and that this, together with the direct induction of apoptosis on tumor cells, is a reason for the inhibition of tumor growth in our system.

Nonmelanoma skin cancer is one of the most common malignancies in humans. Different therapeutic strategies for the treatment of these tumors are currently being investigated. Given the growth-inhibiting effects of cannabinoids on gliomas and the wide tissue distribution of the two subtypes of cannabinoid receptors (CB 1 and CB 2 ), we studied the potential utility of these compounds in anti–skin tumor therapy. Here we show that the CB 1 and the CB 2 receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB 1 /CB 2 agonist WIN-55,212-2 or the selective CB 2 agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells. This was accompanied by impairment of tumor vascularization, as determined by altered blood vessel morphology and decreased expression of proangiogenic factors (VEGF, placental growth factor, and angiopoietin 2). Abrogation of EGF-R function was also observed in cannabinoid-treated tumors. These results support a new therapeutic approach for the treatment of skin tumors.

Proliferation and apoptosis in vivo.

The expression of cannabinoid receptors in epidermal cell lines, normal skin, and skin tumors of mice and humans was examined by Western blot analysis and immunohistochemistry. Western blot experiments showed that CB 1 and CB 2 receptors were expressed in a number of tumorigenic and nontransformed epidermal cell lines of murine and human origin (Figure ​ (Figure1a). 1 a). In addition, the two receptors were present in normal mouse skin as well as in benign (papillomas) and malign (squamous cell carcinomas) mouse skin tumors. Likewise, CB 1 and CB 2 receptors were expressed in human skin, keratinocytes, and carcinomas (Figure ​ (Figure1a). 1 a). To ascertain the specificity of the cannabinoid receptor Ab’s used in the blotting experiments, antigen preabsorption experiments were carried out with the corresponding blocking peptides. As shown in Figure ​ Figure1b, 1 b, the peptides blocked anti-CB 1 and anti-CB 2 Ab binding, not only in skin-derived samples but also in other cell types used as well-established controls for the presence of CB 1 (rat cortical neurons) (18), CB 2 (human promyelocytic HL60 cells) (19), and CB 1 plus CB 2 (rat C6 glioma cells) (21).

The epidermis is a stratified squamous epithelium composed mainly of keratinocytes, whose proliferation and differentiation must be tightly regulated and coordinated. Basal keratinocytes, which are attached to the basement membrane, are undifferentiated and have proliferative potential. Before entering the differentiation program, they withdraw from the cell cycle and migrate toward the surface of the epidermis, leading to the formation of the outermost layer of the epidermis composed of enucleated dead squames, which are continuously shed from the surface of the skin (1). The incidence of both benign and malignant skin neoplasms has been rising at an alarming rate for the past several years. Thus, nonmelanoma skin cancer is one of the most common malignancies in humans: basal cell carcinomas and squamous cell carcinomas represent the vast majority of the malignant tumors diagnosed (2). These tumors are believed to arise mainly from stem cells of hair follicles (3), and their growth and development seems to rely on an early burst of neovascularization (4) in which VEGF (5–7) and EGF-R (8, 9) are essential components. The skin is also a major site for metastasis of internal disease (2, 10). Early recognition, biopsy confirmation, and treatment selection can reduce patient morbidity. Different types of strategies are currently being investigated as therapies for the treatment of these tumors, including cryotherapy, topical chemotherapeutic agents such as 5-fluorouracil, and photodynamics, the success of which is hampered by limitations such as the poor penetration of molecules into the skin and the difficulty to gain access to the whole tumor (10–12).

Immunocytochemical analyses showed that in mouse (Figure ​ (Figure2a) 2 a) and human (Figure ​ (Figure3a) 3 a) normal skin CB 1 and CB 2 receptors were mostly present in suprabasal layers of the epidermis and hair follicles. Basal staining was also observed in some sporadic regions. CB 1 and CB 2 receptor immunoreactivity was also evident in both papillomas and squamous cell carcinomas of mouse origin (Figure ​ (Figure2a), 2 a), as well as in human basal cell carcinomas and squamous cell carcinomas (Figure ​ (Figure3a). 3 a). The specificity of the immunolabeling was shown by experiments in which the primary Ab was omitted and—as mentioned above for Western blots—by antigen preabsorption experiments carried out with the corresponding blocking peptides (Figures ​ (Figures2b 2 b and ​ and3 3 b).

Immunohistochemical analysis of cannabinoid receptor expression in mouse normal skin and skin tumors. ( a ) Immunolocalization of CB 1 and CB 2 receptors. ( b ) Controls without primary Ab (only with secondary biotinylated anti-rabbit Ab), as well as controls with the Ab-blocking peptides, are shown (see Methods and Results for explanation). Normal skin came from a 5-day-old mouse. Papillomas were generated by chemical carcinogenesis (as described in ref. 9), while SCCs were generated by inoculation of PDV.C57 epidermal tumor cells as described in Methods. Images of representative samples are shown. Similar results were obtained in at least two other samples. Hf, hair follicle; bl, basal layer; sbl, suprabasal layers.

We have recently found that in skin carcinomas EGF-R plays an important role in triggering the angiogenic switch necessary for skin tumor growth (9). Thus, we measured the expression levels and activation state of EGF-R in control and cannabinoid-treated skin tumors. While EGF-R mRNA was highly expressed in vehicle-treated tumors, in line with its known overexpression in skin carcinomas (30, 31), the levels of EGF-R mRNA in cannabinoid-treated tumors were very low (Figure ​ (Figure7a). 7 a). In addition, the degree of EGF-R activation (autophosphorylation) was markedly reduced in cannabinoid-treated tumors (Figure ​ (Figure7b). 7 b). Moreover, exposure of cultured PDV.C57 cells to WIN-55,212-2 or JWH-133 blunted EGF-R phosphorylation (Figure ​ (Figure7c), 7 c), supporting the direct impact of cannabinoids on skin tumor cells.

Total RNA was extracted from the tumor samples by the acid guanidinium method (27). The VEGF probe has been described previously (7). The placental growth factor (PIGF) probe was kindly given by G. Persico (Istituto Internazionale di Genetica e Biofisica, Naples, Italy). Probes for angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) detection were kindly provided by G.D. Yancopoulos (Regeneron Pharmaceuticals, Tarrytown, New York, USA). A 1-kb fragment of the 5′ region of the hEGF-R cDNA was used as probe for EGF-R detection (9). Ribosomal 7S RNA was used as a loading control. Densitometric analysis of the blots was performed with a PhosphorImager using Quantity One software (Bio-Rad Laboratories Inc.).

Here we report that CB 1 and CB 2 cannabinoid receptors are expressed in normal epidermis and in skin tumors and that both receptors are functional in the induction of apoptosis of skin tumor cells and the regression of skin carcinomas. It is therefore plausible that apoptosis of tumor cells and tumor regression are two causally related events. Nonetheless, our data indicate that cannabinoid antitumoral action may also rely on the inhibition of tumor angiogenesis. It has been shown that mouse skin tumor growth and progression depends on critical events leading to epithelial and stromal changes, including the establishment of an active angiogenesis (4). Here, we report that blood vessels developed by cannabinoid-treated carcinomas are small, in line with the finding that blood vessel enlargement constitutes a prominent feature of skin tumor progression (4, 32). Moreover, we show that in cannabinoid-treated carcinomas the expression of proangiogenic factors is depressed and that of antiangiogenic factors is unchanged, which fits well with the observations that link skin carcinoma development with a clear imbalance toward positive angiogenic-factor action (6, 7, 9). Ha- ras activation seems to be a critical event in mouse skin tumor initiation as well as a major component of the angiogenic response (6) in which VEGF plays a pivotal role (5, 9). Ha- ras activation induces VEGF expression in mouse keratinocytes (6), as well as in other cell types (33, 34). Our data also show that cannabinoid treatment decreases the expression of PIGF (another VEGF family member) and Ang2, and these two proangiogenic factors may act in concert with VEGF because their expression is highly increased since the early stages of tumor development (9, 28, 29).

Cannabinoids inhibit angiogenesis in skin tumors in vivo. PDV.C57 cells were injected subcutaneously in mice. When tumors had reached the desired size, animals were treated with either vehicle (Co), WIN-55,212-2 (WIN,) or JWH-133 (JWH) for 11 days. ( a ) Northern blot of the proangiogenic factors VEGF, PIGF, and Ang2. C1, C2; J1, J2; W1, W2 designate tumors from two different animals of each experimental group, that is, treated with vehicle (Co), JWH-133, or WIN-55,212-2, respectively. OD values relative to those of loading controls are given in arbitrary units. 7S, Ribosomal 7S RNA. ( b ) CD31 immunostaining. Note that control carcinomas show dilated blood vessels, while vessels of cannabinoid-treated tumors are narrow. ( c ) Morphometric analysis of tumor vasculature ( n = 4–6 for each experimental group). *Significantly different ( P < 0.05) from control mice.

Tissues were fixed in 10% buffered formalin and embedded in paraffin. Sections of mouse and human skin and tumors were stained with the aforementioned Ab’s against CB 1 (1:300) and CB 2 (1:300) receptors. Control immunostainings using the secondary Ab in the absence of the primary Ab were routinely performed. In addition, antigen preabsorption experiments were carried out with the corresponding blocking peptides as described above. Immunodetection of blood vessels in cryosections of mouse tumors was performed with an anti-CD31 Ab (1:40; PharMingen, San Diego, California, USA). Sections were incubated with a biotinylated anti-rabbit (CB 1 and CB 2 ) or anti-rat Ab (CD31) and then with peroxidase-conjugated streptavidin (LSAB Kit Peroxidase; DAKO A/S, Glostrup, Denmark). Ab localization was determined using 3,3′-diaminobenzidine (Vector Laboratories, Burlingame, California, USA). Morphometric values were obtained by examination of six 0.11-mm 2 sections per tumor with the image analysis system Leica Qwin (Leica Microsystems Inc., Chantilly, Virginia, USA).

Immunohistochemistry.

1 Project on Cellular and Molecular Biology and Gene Therapy, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain 2 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain 3 Department of Pathology, Hospital General de Móstoles, Madrid, Spain 4 Department of Chemistry, Clemson University, Clemson, South Carolina, USA.

1 Project on Cellular and Molecular Biology and Gene Therapy, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain 2 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain 3 Department of Pathology, Hospital General de Móstoles, Madrid, Spain 4 Department of Chemistry, Clemson University, Clemson, South Carolina, USA.

1 Project on Cellular and Molecular Biology and Gene Therapy, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain 2 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain 3 Department of Pathology, Hospital General de Móstoles, Madrid, Spain 4 Department of Chemistry, Clemson University, Clemson, South Carolina, USA.

Nonmelanoma skin cancer is one of the most common malignancies in humans. Different types of strategies are currently being investigated as therapies for the treatment of these tumors, including cryotherapy, topical chemotherapeutic agents such as 5-fluorouracil, and photodynamics, the success of which is hampered by limitations such as the poor penetration of molecules into the skin and the difficulty of gaining access to the whole tumor (10–12). The present data indicate that local cannabinoid administration may constitute an alternative therapeutic approach for the treatment of nonmelanoma skin cancer. Of further therapeutic interest, we show that skin cells express functional CB 2 receptors. The synergy between CB 1 and CB 2 receptors in eliciting skin tumor cell apoptosis reported here is nonetheless intriguing because it is not observed in the case of cannabinoid-induced glioma cell apoptosis (21, 22). In any event, the present report, together with the implication of CB 2 – or CB 2 -like receptors in the control of peripheral pain (40–42) and inflammation (41), opens the attractive possibility of finding cannabinoid-based therapeutic strategies for diseases of the skin and other tissues devoid of nondesired CB 1 -mediated psychotropic side effects.

1 Project on Cellular and Molecular Biology and Gene Therapy, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain 2 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain 3 Department of Pathology, Hospital General de Móstoles, Madrid, Spain 4 Department of Chemistry, Clemson University, Clemson, South Carolina, USA.

For proliferation assays, mice received an intraperitoneal injection of BrdU (120 mg/kg body weight) (Boehringer Mannheim GmbH) 2 hours before tumor harvesting. Detection of BrdU-positive cells was performed using an anti-BrdU mouse mAb (Boehringer Mannheim GmbH) as described (9). Apoptosis was determined by TUNEL staining (Boehringer Mannheim GmbH) according to kit manufacturer’s instructions (21).

Jesús Martínez-Palacio.

Conflict of interest: The authors have declared that no conflict of interest exists.

This background prompted us to explore whether (a) the skin and skin tumors express cannabinoid receptors; (b) cannabinoid receptor activation exerts a growth-inhibiting action on skin tumors in vivo; and (c) inhibition of angiogenesis is implicated in the anti-tumoral effect of cannabinoids. Our data show that (a) CB 1 and CB 2 receptors are present in the skin and skin tumors; (b) local cannabinoid receptor activation induces the regression of skin tumors in vivo; and (c) at least two mechanisms may be involved in this action: direct apoptosis of tumor cells and inhibition of tumor angiogenesis.

Because cannabinoid-based therapeutic strategies should be as devoid as possible of psychotropic side effects and PDV.C57 express functional CB 2 receptors, we administered to mice the selective CB 2 agonist JWH-133. Previously, we have provided pharmacological, biochemical, and behavioral evidence that JWH-133 activates selectively the CB 2 receptor and does not elicit psychotropic effects in mice (22). As shown in Figure ​ Figure5, 5 , a–c, tumors from JWH-133–treated animals were significantly smaller than those from vehicle-treated controls (in ≈70% of the mice treated).

Immunohistochemical analysis of cannabinoid receptor expression in human normal skin and skin tumors. ( a ) Immunolocalization of CB 1 and CB 2 receptors. ( b ) Controls without primary Ab (only with secondary biotinylated anti-rabbit Ab), as well as controls with the Ab-blocking peptides, are shown (see Methods and Results for explanation). The source of samples is described in Methods. BCC, basal cell carcinoma; SCC, squamous cell carcinoma; Hf, hair follicle.

We next examined whether, as occurs in cultured skin tumor cell lines, cannabinoids induce apoptosis of malignant cells in vivo. As shown in Table ​ Table1, 1 , quantification of apoptotic cells in tumor sections revealed that treatment with WIN-55,212-2 or JWH-133 increased the number of apoptotic cells. In contrast, the proliferation index did not significantly differ between control and cannabinoid-treated carcinomas.

Western blot analysis of cannabinoid receptor expression in normal skin and skin tumors. ( a ) CB 1 and CB 2 receptor expression in murine and human epidermal cell lines, normal skin, and skin tumors. ( b ) Controls with the anti-CB 1 or anti-CB 2 Ab-blocking peptide are shown (see Methods and Results for explanation). Mouse papillomas were generated by chemical carcinogenesis (as described in ref. 9), while mouse squamous cell carcinomas (SCCs) were generated by inoculation of PDV.C57 epidermal tumor cells as described in Methods. The source of human samples is described in Methods. Images of representative samples are shown. Similar results were obtained in at least two other blots. PB, immortalized mouse nontumorigenic cell line derived from SENCAR mice papillomas; HK, human keratinocytes; m, mouse; h, human.

1 Project on Cellular and Molecular Biology and Gene Therapy, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain 2 Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain 3 Department of Pathology, Hospital General de Móstoles, Madrid, Spain 4 Department of Chemistry, Clemson University, Clemson, South Carolina, USA.