Cannabinoids in Integumentary Wound Care: A Systematic Review of Emerging Preclinical and Clinical Evidence
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Eligibility Criteria
2.3. Quality Assessment
3. Results
3.1. Search Results
3.2. General Characteristics of the Selected Studies
3.3. Quality of the Selected Studies
3.4. In Vivo Studies
3.5. Human Studies
4. Discussion
4.1. In Vivo Studies
4.1.1. Major Effects on Wounds
4.1.2. Other Effects on Wounds
4.1.3. Side Effects
4.2. Human Studies
4.2.1. Major Effects on Wounds
4.2.2. Other Effects on Wounds
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study Setting and Location | Study Design | Method/Assay | Intervention | Outcome Measure(s) | Treatment Outcome(s) | Quality Score |
---|---|---|---|---|---|---|
Mehrabani et al. 2016 [131] In vivo, laboratory-reared | Experimental | Third-degree burns in mice. Experimental group 25% of the total body surface area of the male albino mice (n = 8 per group, 6–8 weeks old) was burnt by boiling water. | Treatment Formulation (100 mg/mouse) containing a combination of the oils of sesame (Sesamum indicum L.) seed (60%), wild pistachio (Pistacia atlantica Desf.) fruit (20%), hemp (Cannabis sativa L.) fruit (12%), and walnut (Juglans regia L.) seed (8%) was applied topically twice daily for 21 days. Comparator Topical SSD * twice daily (200 mg/kg/day, as positive control), Untreated group (negative control) | Wound area, rate of wound healing, epithelialisation time, percentage of wound contraction. | Significant wound contraction was observed with the formulation on days 10 (65.9 ± 3.8%), 14, 18, and 21 (99.5 ± 0.8%) compared to SSD and untreated groups (p < 0.001). Epithelialisation time was significantly decreased by the formulation (formulation = 20.5 ± 1.37 days, untreated group 25.5 ± 0.83 days) (p < 0.001). The formulation resulted in improved skin re-epithelialisation, granulation tissue formation, scattered inflammatory cells infiltration, and collagenization on day 21. The collagenization and epithelialisation were significantly higher in the formulation group compared to SSD * group on day 21 (p-value is not given). No scar formation. | 1 |
Wang et al. 2016 [67] In vivo, laboratory-reared | Experimental | Full-thickness skin wound in mice. Experimental group Two full-thickness excisions (6 mm diameter) were made symmetrically on the dorsal skin of 8-week-old male BALB/c mice (20–25 g). After the surgery, mice received daily treatments and were euthanized at 0.5, 1, 3, 5, 7, 10, 13, 17, and 21 days post-injury (6 mice at each time point). | Treatment Daily intraperitoneal injections of Gp1a (3 mg/kg, dissolved in vehicle). Comparator Daily intraperitoneal injections of vehicle (5% dimethyl sulfoxide/2% Tween-80/physiological saline, 2.5 μL/g), or AM630 (3 mg/kg, dissolved in vehicle). Six mice without surgery were used as controls. | Percentage wound size, wound re-epithelialisation percentage. | GP1a inhibited wound contraction after decrustation. Wound sizes in GP1a group were significantly larger than in the vehicle group on days 10–21 post-injury (p < 0.05). No significant difference in wound size was observed between AM630 and vehicle group. Wound re-epithelialisation was accelerated in GP1a group compared to other two groups (p < 0.05). Complete re-epithelialisation was reported in all 3 groups by day 13. In AM630 group, wound re-epithelialisation was delayed compared to vehicle control on days 5–7 (p < 0.05). The dermal scar in the GP1a group was thinner and the collagen fibres were much slenderer. AM630 group showed similar epidermal and dermal morphologies with vehicle group. | 1 |
Klein et al. 2018 [132] In vivo, laboratory-reared | Experimental | Oral wound healing in rats. Experimental group Male Wistar rats (Rattus novergicus) (~ 90 days old, ~ 300 g, n = 10 per group) with an induced ulcer on the ventral tongue. | Treatment Intraperitoneal injection of CBD ** (5 or 10 mg/kg body weight) was initiated immediately after ulcer induction and repeated daily for 3 or 7 days. Comparator Vehicle (2% Tween 80 in saline) for 3 or 7 days. | Wound area, presence of oedema, hyperaemia and inflammatory infiltrate (by histological examination). | Wound size was not significantly different from that of the respective control group on any of the test dates. Significantly lower inflammation was observed by histological examination in CBD treatment groups compared to the control group (p < 0.05) on day 3. A significant difference in inflammation was not observed within the groups on day seven by histological examination. Higher re-epithelialisation (angiogenesis, fibroplasia, collagen fibres deposited in a well-arranged manner, thicker marginal epithelium, hyperkeratinisation) was observed in CBD-treated groups by histological examination on day seven. These histological changes were not sufficient to provide clinical improvement in the wound. No side effects were observed. | 1 |
Koyama et al. 2019 [134] In vivo, laboratory-reared | Experimental | Full-thickness skin wound in mice. Experimental group Full-thickness excisions (< 5 mm × 5 mm) were made on the backs of 8–10-week-old adult female C57BL/6J mice and a silicone ring was attached to the lesion by a liquid sealing bandage (serving as a reservoir for the treatment). They were treated daily. On day five following the surgery, the skin was harvested and stained with a K14 (a marker of re-epithelialisation) antibody. | Treatment Topical 1 μM JWH133 (CB2R agonist, 50 μL) in olive oil daily (n = 13) for five days Comparator Topical olive oil (vehicle) daily (n = 16). | Distance of cell migration from the wound edge. | JWH133 enhanced re-epithelialisation compared to the vehicle control group (p = 0.071). | 1 |
McIver et al. 2020 [133] In vivo, field, contaminated wound | Experimental | The second intention wound healing in the equine model. Experimental group 6 adult Standardbred horses (3 geldings, 3 mares, 3–10 years old) with five 2.5 cm × 2.5 cm full-thickness skin wounds on the dorsomedial aspect of the metacarpi (three wounds on a forelimb, two wounds on the contralateral forelimb) contaminated with faeces for 24 h under a bandage. | Treatment Topical application of 1% CBD ** in UMF *** 5 manuka honey (2 mL) daily for 42 days. Wounds were bandaged daily in the first 13 days. Comparator UMF 5 manuka honey (vehicle, 2 mL), UMF 20 manuka honey (2 mL), or 0.9% sterile saline (2 mL) daily for 42 days. | Wound area, overall time to complete healing, overall rate of wound healing (cm2/day). | Total days for healing (CBD: 84 days, other groups: 83–88 days) and overall healing rates (0.1 cm2/day) were similar across all treatment groups. | 1 |
Blaskovich et al. 2021 [135] In vivo, laboratory-reared | Experimental | Bioluminescent in vivo mouse skin infection model for acute wounds. Experimental group Skin of the back was shaved and disrupted in immunocompromised adult female CD1 mice (n = 6 per group) and was inoculated with 10 μL Staphylococcus aureus Xen-29 bioluminescent bacteria (5 × 107 CFU ****). | Treatment Formulations of 5% CBD formulation (either BTX 1503, 1503 gel, or BTX 1204 gel, 50 μL) topically at 0 (initiated immediately after inoculation), 12, 24, and 32 h post-infection. Comparator 2% mupirocin (50 μL) or vehicle (50 μL). | 48 h after the first treatment and infection, animals were sacrificed, and the skin assessed for signs of gross pathology, CFU’s per mice. Bioluminescent in vivo imaging was performed pre-infection and then at 4, 24, 36, and 48 h post-infection. | 5% CBD significantly reduced S. aureus load at 48 h compared to vehicle (p = 0.0184). 2% mupirocin was more effective than 5% CBD formulations tested (I = <0.0001 for mupirocin vs. vehicle). | 1 |
Zhao et al. 2021 [137] In vivo, laboratory-reared | Experimental | Full-thickness skin wound in mice. Experimental group 3M transparent ventilation tape was placed around the operative area of 6-week-old (18–22 g) male wild-type BALB/c mice. Two full-thickness circular punch wounds (4 mm diameter) were made symmetrically over the midline of the dorsum. Then, the wounds in each mouse were treated: one with Gp1a-gel and the other with scramble Tm hydrogel (vehicle). Six mice were sacrificed from each group at 4, 8, 12, and 20 days post-surgery. | Treatment 50 μL of 4 mg/mL Gp1a-gel applied once after the surgery. Comparator 50 μL scramble Tm hydrogel (vehicle) applied once after the surgery. | Length of epithelial sheet, time to complete wound healing. | GP1a gel resulted in a significantly longer epithelial sheet compared to vehicle from days 4 to 6 post-surgery (p < 0.05). Complete wound healing was achieved in 5–7 days, with earlier wound closure observed with GP1a gel compared to the vehicle in the same mouse. | 1 |
Zheng et al. 2022 [138] In vivo, laboratory-reared | Experimental | Full-thickness skin wound in rats. Experimental group Two full-thickness circular punch wounds (10 mm diameter) were made on the dorsal region of the 8–10-week-old (200–250 g) male Sprague Dawley rats. Four different treatments were, respectively, applied to the wounds (n = 6 per group) and the wound beds were covered with medical gauze. The state of wound healing was recorded on days 0, 3, 7, 10, and 14 post-surgery. | Treatment 2% w/v CBD/Alg@Zn (cannabidiol containing alginate–zinc hydrogel) applied once after the surgery. Comparator Normal saline group (control), Alg@Zn group (or alginate-Zn hydrogel, vehicle), or Tegaderm™ group (or 3M, commercial wound dressing) applied once after the surgery. | Percentage of remaining wound area. | Significant reduction in wound size on day 7 by CBD/Alg@Zn compared to other treatments (p < 0.05). CBD/Alg@Zn showed faster wound healing compared to other groups although not statistically significant. Percentages of remaining wound area on day 10 were 34.3 ± 2.9 for the control group, 25.8 ± 2.0 for the 3M group, 17.1 ± 2.1 for the Alg@Zn group, and 13.7 ± 2.7 for the CBD/Alg@Zn group. Wounds were not completely healed on day 14 in any of the groups. On day 14, CBD/Alg@Zn had the lowest remaining wound area compared to other groups, although not statistically significant. Angiogenesis and hair follicle structures were observed with CBD/Alg@Zn on day 14. | 1 |
Zhong et al. 2022 [139] In vivo, laboratory-reared | Experimental | Experiment A: in vivo mouse skin infection model for acute wounds. Experimental group The skin of the back of 6-week-old female BALB/c mice (n = 5 per group) was shaved, and circular wound (~10 mm) was made. Methicillin-resistant Staphylococcus aureus (MRSA) cells (108 CFU ****) were coated on wounds, and continuously infected for two days. Medicine-free band-aids were used to fix the MRSA and nanoparticles on wounds. Wounds were treated every two days. On the second day, liquid on wound site was absorbed with a sterile cotton swab and plated on a culture dish. | Treatment 100 μL of CBD (10 μg/mL), or 100 μL of Chi@HMPB@CBD NPs (CBD-loaded hollow mesoporous Prussian blue nanoparticles coated with chitosan; containing 100 μg/mL HMPB NPs) topically every two days up to day 7. Prior to fixing the wounds, Chi@HMPB@CBD plus laser groups were irradiated with an 808 nm laser (1 W/cm2, 3 min) and treated with 100 μL of Chi@HMPB@CBD topically every two days up to 7 days. Comparator 100 μL of PBS (control), or 100 μL of Chi@HMPB NPs (hollow mesoporous Prussian blue nanoparticles coated with chitosan), applied topically every two days up to day 7. | Relative wound size, CFU count in the wound on day 2 of treatment. | Significant reduction in CFU on day 2 of treatment by Chi@HMPB@CBD compared to control group, and by Chi@HMPB@CBD plus laser group compared to Chi@HMPB@CBD group. Significant reduction in relative wound size by Chi@HMPB@CBD plus laser compared to the control group on day 5. Complete wound closure was not observed in any of the groups by day 9. CBD resulted in lower relative wound size compared to the control group on all the days, although not statistically significant. Chi@HMPB@CBD resulted in lower relative wound size compared to Chi@HMPB on all the days, although not statistically significant. Chi@HMPB@CBD plus laser resulted in lower relative wound size compared to Chi@HMPB@CBD on all the days, although not statistically significant. No significant differences in body weight were observed. CBD resulted in a significant increase in WBC count on day 11. | 1 |
Zhong et al. 2022 [139] In vivo, laboratory-reared | Experimental | Experiment B: in vivo mouse skin infection model for chronic wounds. Experimental group Similar to above, using 6-week-old female MKR mice with induced type 2 diabetes. | Similar to above. | Similar to above. | Relative wound size in Chi@HMPB@CBD plus laser group was significantly less compared to the control group on days 7, 9, and 11. Complete wound closure by Chi@HMPB@CBD plus laser group on day 11, which was significant compared to the control group. CBD resulted in lower relative wound size compared to the control group on all the days, although not statistically significant. ~55.2% and ~98.3% of bacteria were killed in the Chi@HMPB@CBD NPs and Chi@HMPB@CBD NPs plus laser groups on day 2 respectively. Chi@HMPB@CBD resulted in significant reduction in CFU count compared to control on day 2 (p < 0.001). Chi@HMPB@CBD NPs plus laser groups resulted in significant reduction in CFU count compared to Chi@HMPB@CBD on day 2 (p < 0.001). No significant differences in body weight were observed. | 1 |
McCormick et al. 2023 [140] In vivo, laboratory-reared | Experimental | Experiment A: Murine model of cutaneous lupus erythematosus (prophylactic). Experimental group 10-week-old female MRL/lpr mice, which spontaneously develop generalized autoimmune disease including skin lesions clinically and histologically similar to cutaneous lupus erythematosus were used. Mice were sacrificed at 20 weeks. | Treatment 50 mg of 1% Anandamide loaded into a silica nanoparticle in coconut oil (AEA-NP, n = 10) was topically applied to interscapular region twice daily for 10 weeks. Comparator 50 mg of silica nanoparticle in coconut oil (NP, vehicle, n = 10) was topically applied to interscapular region twice daily for 10 weeks, and untreated controls (n = 5). | Lesion score for developing lesions and severity of existing lesions (erythema, thickness, scaling, and alopecia). | Significantly lower final lesion severity scores after 10 weeks of treatment with AEA-NP (M = 1.87 ± 1.82) compared to vehicle (M = 5.65 ± 2.86, p < 0.01) and untreated controls (M = 9.2 ± 4.65, p < 0.01). | 1 |
McCormick et al. 2023 [140] In vivo, laboratory-reared | Experimental | Experiment B: Murine model of cutaneous lupus erythematosus (interventional). Experimental group Female MRL/lpr mice from 8 weeks of age with developed skin lesions with skin plaque score of 1 were enrolled and treated for 10 weeks. | Treatment 50 mg of either 1% AEA-NP in coconut oil (n = 10) or 1% unencapsulated anandamide in coconut oil (AEA-UE; n = 10) twice weekly for 10 weeks applied topically on head and interscapular area. Comparator Untreated controls (n = 10). | Weekly lesion score (erythema, thickness, scaling, and alopecia). | AEA-NP resulted in lower average skin lesion scores compared to untreated controls from week 3 of treatment (p < 0.05) until the end of the treatment period (week 4–10 p < 0.0001). AEA-NP had significantly lower average skin lesion scores than AEA-UE mice from weeks 5–10 of treatment (p < 0.05). AEA-UE resulted in lower skin scores compared to untreated controls from weeks 2–10. | 1 |
Cham et al. 2024 [136] In vivo, laboratory-reared | Experimental | In vivo mice dermal infection model Experimental group The skin of the area for the infection was depilated and a blood oozing patch was created on 3–4-week-old male Balb/c mice (22–26 g). An overnight-grown culture of MRSA-15187 equivalent to 0.5 McFarland standard in normal saline was applied for 24 h on the abraded skin. | Treatment 0.5% Tetrahydrocannabidiol (THCBD) formulated in a PEG-400 ointment base (n = 15), or 2% THCBD formulated in a PEG-400 ointment base (n = 15) was applied twice daily for 5 days. Comparator 2% mupirocin (positive control group, n = 15), or control (drug-free control, n = 18) twice daily for 5 days | Number of CFU **** in a dissected 1 cm2 skin patch. | 2% THCBD and mupirocin reduced initial bacterial load by ∼4-log on days 2 and 3, respectively. 0.5% THCBD resulted in a 2-log CFU reduction on day 2. All the treatments resulted in >3-log reduction by day 4 and reduced the bacterial load to minimum by day 5. | 1 |
Reference | Formulation and/or Route of Administration | Content |
---|---|---|
Mehrabani et al. 2016 [131] | Topical formulation | Oils of sesame (Sesamum indicum L.) seed (60%), wild pistachio (Pistacia atlantica Desf.) fruit (20%), hemp (Cannabis sativa L.) fruit (12%), and walnut (Juglans regia L.) seed (8%). Dose: 100 mg/mouse. |
Wang et al. 2016 [67] | Intraperitoneal injection | Gp1a dissolved in 5% dimethyl sulfoxide/2% Tween-80/physiological saline. Dose: 3 mg/kg body weight. |
Klein et al. 2018 [132] | Intraperitoneal injection | Synthetic CBD * (≥99 purity) dissolved in 2% polyoxyethylene sorbitan monooleate (Tween 80) in saline. Immediately prepared before administration in a volume of 1 mL/kg. Protected from light. Dose: 5 or 10 mg/kg body weight. |
Koyama et al. 2019 [134] | A silicone ring was attached to the lesion by a liquid sealing bandage (serving as a reservoir for the treatment) Topical | 1 μM JWH133 in olive oil daily for 5 days. Dose: 50 μL/day. |
McIver et al. 2020 [133] | Topical | Daily application of 1% CBD * extract (= 10 mg CBD) in UMF ** 5 manuka honey for 42 days with initial 13 days of bandaging. Dose: 2 mL/day. |
Blaskovich et al. 2021 [135] | Topical | 5% synthetic CBD * either in BTX 1503, 1503 gel, or BTX 1204 gel. Dose: 50 μL. |
Zhao et al. 2021 [137] | Topical | 4 mg/mL Gp1a in scramble Tm hydrogel. Dose: 50 μL. |
Zheng et al. 2022 [138] | Topical | 2% w/v CBD * containing alginate-Zn hydrogel. Dose: not given. |
Zhong et al. 2022 [139] | Topical | Natural CBD * (10 μg/mL), Chi@HMPB NPs (hollow mesoporous Prussian blue nanoparticles coated with chitosan), Chi@HMPB@CBD NPs (CBD-loaded hollow mesoporous Prussian blue nanoparticles coated with chitosan; containing 100 μg/mL HMPB NPs). Prior to fixing the wounds, Chi@HMPB@CBD plus laser groups were irradiated with an 808 nm laser (1 W/cm2, 3 min). Dose: 100 μL. |
McCormick et al. 2023 [140] | Topical | 1% Anandamide loaded into a silica nanoparticle in coconut oil (AEA-NP), 1% unencapsulated AEA in coconut oil twice weekly (AEA-UE). Dose: 50 mg. |
Cham et al. 2024 [136] | Topical | Tetrahydrocannabidiol (>99% purity, synthetic) formulated in a PEG-400 ointment base (0.5% and 2%). Dose: not given. |
Study Setting and Location | Study Design | Study Population | Wound Aetiology/Classification | Intervention Descriptions | Outcome Measures | Follow-up | Study Outcomes | Quality Score | |
---|---|---|---|---|---|---|---|---|---|
Test | Comparator | ||||||||
Maida and Corban 2017 [144] Ambulatory setting, Canada | Prospective case series | Patients suffering from Pyoderma Gangrenosum (n = 3), mean age = 62 years, gender = 2 females and 1 male. | Pyoderma gangrenosum in lower extremities. | 0.5–1 mL of topical medical cannabis oil (5–7 mg/mL THC * and 6–9 mg/mL CBD **) applied to the wound bed 1–2 times a day. Then, wounds were bandaged. Treatment was tailored to the patient’s needs. | Condition before the treatment. | Reduction in average daily pain score, reduction in average daily morphine (MSE ***) usage. | Not reported. | Statistically significant reduction (p < 0.05) in the average daily pain score was observed in two patients. A clinically significant reduction (>60%) in average daily pain score was observed in all the patients. A substantial reduction in average daily MSE *** usage was observed (p < 0.05). | 5 |
Chelliah et al. 2018 [141] Community setting, US | Case report, observational | Paediatric epidermolysis bullosa patients (n = 3), mean age = 4.5 years, gender = 2 females and 1 male. | Chronic non-healing epidermolysis bullosa wounds. | CBD ** oil (alone or mixed with emu oil) applied topically on the blisters 2–3 times daily. Self-initiated treatment. | Condition before the treatment. | Healing time, reduction in blistering, reduction in pain. | Not reported | Decreased blistering, decreased healing time, reduction in pain, stopped other analgesics, and improved ambulation (p values are not given). No significant side effects were reported. | 6 |
Schrader et al. 2019 [143] Ambulatory setting, The Netherlands | Open-label trial | Patients suffering from epidermolysis bullosa (n = 3), mean age = 47, gender = 2 males and a female. | Chronic epidermolysis bullosa. | Whole C. sativa plant extract, containing 20 mg/mL CBD **, 13 mg/mL THC *, dissolved in refined peanut oil (arachis oil) [149]. Treatment was tailored to the patient needs. | Condition before the treatment. | Reduction in pain, reduction in pruritus, reduction in the overall intake of analgesic medications. | 8 months–2 years | Reduced pain scores (from 9 out of 10 to 1–4 out of 10), Reduction in pruritus, discontinuation or reduction in other analgesics and amitriptyline (p values are not given). Side effects: increased appetite. | 6 |
Maida et al. 2020 [142] Ambulatory setting, Canada | Prospective open-label cohort study. | Patients with non-uremic calciphylaxis leg ulcers (number of patients = 2, number of wounds = 3), The mean age is 77 years, 2 females. | Painful, non-healing, non-uremic calciphylaxis leg ulcers of more than six months of duration. | Wounds were gently cleansed with sterile normal saline daily. Formulations VS-12 **** and VS-14 ***** were applied daily to the wound beds and 4–6 cm radial cuff of peri-wound area, respectively, until complete wound closure. Both formulations contained CBD ** (3.75 mg/mL), THC * (<1 mg/mL), quercetin (31.25 mg/mL), disomin (25.31 mg/mL), hesperidin (2.5 mg/mL), and β-caryophyllene (152.69 mg/mL) in different bases. Wounds were covered with a layer of Jelonet and Mesorb (dressings), then by spiral bandaging. | Opioid for analgesic use before the treatment. | Wound healing/full closure, time for complete wound closure, reduction in pain, reduction in analgesic opioid usage. | Until complete wound closure. | 50% wound closure after 32–41 days. Complete wound closure after a mean of 76.3 days. Re-epithelialisation rate was 1.5–1.8%/day. 33% reduction in analgesic usage by 18–19 days (clinically significant). Analgesics were no longer required after a mean of 63 days. Improved ambulation (p values are not given). No significant side effects were reported. | 7 |
Maida et al. 2021 [145] Ambulatory setting, Canada | Open-label trial | Patients suffering from venous leg ulcers, (number of patients = 14; number of wounds = 16); mean age = 75.8 years; gender = 8 females and 6 males. | Chronic and non-healing leg ulcers. These did not respond to a minimum of 4 weeks of compression therapy with all available best practices (local treatments). | Wounds were gently cleansed with sterile normal saline every two days. Formulations VS-12 **** and VS-14 ***** were applied to the wound beds and 4–6 cm radial cuff of peri-wound area, respectively, every two days. Then, the wounds were bandaged with a layer of Jelonet® and Mesorb®. Then, an inelastic compression bandage was applied. | None. | Complete wound closure, healing time. | Until complete wound closure. | The median time for complete wound healing was 34 days. The closing time for wounds 0–10 cm (n = 6 wounds) in size was reported to be 38 days, while the treatment for wounds >10 cm (n = 10 wounds) was estimated to be 29 days. 81% of wounds were closed completely (others were lost to follow-up). The median rate of surface area change was −3.3 cm2/30 days (p values are not given). No patient developed hypertrophic scars or keloids. No significant side effects were reported. | 6 |
Diaz et al. 2021 [146] Ambulatory setting, Canada | Case report, observational | A 37-year-old female patient with a pressure ulcer. | Progressively worsening pressure ulcer between right iliac crest and right rib cage for 5 years, unresponsive to multiple interventions including wound dressings, antibiotics, and topical treatments. | Three oral medicinal cannabis oils containing THC and CBD at different times of the day. THC and CBD daily doses were gradually increased and stabilized over time from 0.11 mg/kg THC and 0.48 mg/kg CBD in week 1 to 0.67 mg/kg THC and 1.28 mg/kg CBD in week 8. A foam-padded dressing (Allevyn; Smith + Nephew) was also used to relieve pressure on the wound. | Condition before the treatment. | Complete wound closure, healing time. | 2 months. | Reduction in wound size, pain, and erythema was reported within 2 weeks of treatment initiation. Complete wound healing was achieved in 2 months. Improved sleep quality and decreased anxiety were reported. The presence or absence of side effects was not reported. | 6 |
Umpreecha et al. 2023 [147] Ambulatory setting, Thailand | Randomized, parallel double-blind, controlled trial. | Patients with recurrent aphthous ulcers at least 2 times/year on nonkeratinized oral mucosa, aged 18–65 years (n = 69). | 1–3 minor (2–10 mm in diameter) aphthous ulcers of ≤48 h duration with easy access for evaluation. | 0.1% CBD ** oral paste applied to ulcers with a provided calibrated spoon 3 times per day after meals for 7 days. | Control groups received 0.1% triamcinolone acetonide (TA), or placebo applied similarly. | Ulcer size, daily pain ratings. | 7 days. | Pseudomembranous ulcer size and erythematous border size were increased with placebo until day 5 and then began to reduce. Ulcer size and erythematous border size were reduced with both CBD and TA compared to initial size over time. Statistically significant ulcer size and erythematous border size reductions were observed with CBD and TA compared to placebo on days 2, 5, and 7. CBD significantly reduced the pain levels on day 5 compared to placebo (p < 0.05). TA significantly reduced the pain levels on days 4, 5, and 7 compared to placebo (p < 0.05). Compared to CBD, TA better reduced the ulcer size and erythematous border sizes. No side effects (local or systemic) were reported. | 10 |
Reference | Formulation and Route of Administration | Content |
---|---|---|
Maida and Corban 2017 [144] | Topical oil | THC * (5 or 7 mg/mL) and CBD ** (6 or 9 mg/mL) in sunflower oil [(ARGYLETM THC 5 mg/mL and CBD 6 mg/mL) from TWEED Inc.; BedroliteTM (THC 7 mg/mL and CBD 9 mg/mL) from Bedrocan Inc.] |
Chelliah et al. 2018 [141] | Different topical formulations such as spray (oil), oil, and cream | CBD ** oil with or without emu oil |
Schrader et al. 2019 [143] | Sublingual oil | Whole Cannabis sativa plant extract, containing 20 mg/mL CBD **, 13 mg/mL THC *, dissolved in refined peanut oil (arachis oil) [149] |
Maida et al. 2020 [142] | Topical formulations | Formulation VS-12 *** (base: 1:1 v/v hyaluronic acid and Aloe vera gel) applied to the wound beds. Formulation VS-14 **** (liposomal base) were applied to 4–6 cm radial cuff of peri-wound integument. Both formulations contain CBD ** (3.75 mg/mL), THC * (<1 mg/mL), quercetin (31.25 mg/mL), diosmin (25.31 mg/mL), hersperidin (2.5 mg/mL), and β-caryophyllene (152.69 mg/mL) |
Maida et al. 2021 [145] | Topical formulations | Same as above |
Diaz et al. 2021 [146] | Oral oil | CBD ** dominant oil: Yellow Cannabis Oil, 1:20 THC:CBD (Spectrum Therapeutics) for daytime use. THC * dominant oils: Red No. 1 Oil, 26.3:0 THC:CBD (Spectrum Therapeutics), and Red No. 2 Oil, 26.3:0 THC:CBD (Spectrum Therapeutics) for use in the daytime and just before sleep |
Umpreecha et al. 2023 [147] | Oral paste | 0.1% CBD (natural) oral paste |
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Niyangoda, D.; Muayad, M.; Tesfaye, W.; Bushell, M.; Ahmad, D.; Samarawickrema, I.; Sinclair, J.; Kebriti, S.; Maida, V.; Thomas, J. Cannabinoids in Integumentary Wound Care: A Systematic Review of Emerging Preclinical and Clinical Evidence. Pharmaceutics 2024, 16, 1081. https://doi.org/10.3390/pharmaceutics16081081
Niyangoda D, Muayad M, Tesfaye W, Bushell M, Ahmad D, Samarawickrema I, Sinclair J, Kebriti S, Maida V, Thomas J. Cannabinoids in Integumentary Wound Care: A Systematic Review of Emerging Preclinical and Clinical Evidence. Pharmaceutics. 2024; 16(8):1081. https://doi.org/10.3390/pharmaceutics16081081
Chicago/Turabian StyleNiyangoda, Dhakshila, Mohammed Muayad, Wubshet Tesfaye, Mary Bushell, Danish Ahmad, Indira Samarawickrema, Justin Sinclair, Shida Kebriti, Vincent Maida, and Jackson Thomas. 2024. "Cannabinoids in Integumentary Wound Care: A Systematic Review of Emerging Preclinical and Clinical Evidence" Pharmaceutics 16, no. 8: 1081. https://doi.org/10.3390/pharmaceutics16081081