Cannabinoids for Dermatological Applications: Mechanistic Insights, Clinical Evidence, and Emerging Nanotechnology-Enabled Delivery Strategies

“Cannabinoids (CBs) derived from Cannabis sativa have attracted growing interest for dermatological applications due to their anti-inflammatory, antiproliferative, antimicrobial, antifibrotic, and antipruritic properties. However, their clinical translation is significantly limited by physicochemical and pharmacokinetic challenges, including poor aqueous solubility, lipophilicity, instability, variable skin penetration, and inconsistent bioavailability.

At the molecular level, CBs modulate keratinocyte proliferation, sebocyte activity, fibroblast function, melanocyte balance, and immune signalling through CB1/CB2 receptors, TRP channels, and PPARγ pathways.

Evidence supports their potential in the treatment of psoriasis, atopic dermatitis, acne, allergic contact dermatitis, pruritus, scleroderma, and skin cancers. Clinical evidence remains preliminary: topical and oral formulations have demonstrated anti-inflammatory, antiproliferative, antibacterial, and antifibrotic effects, with improvements in pruritus, lesion severity, and quality of life in early-phase studies. However, most trials are small, uncontrolled, and lack placebo comparators, limiting generalisability.

To overcome formulation barriers and enhance dermal delivery, advanced pharmaceutical strategies such as liposomes, nanoemulsions, polymeric nanoparticles, micelles, and transdermal systems have been investigated to improve stability, controlled release, and targeted skin deposition while minimising systemic exposure.

This review integrates mechanistic insights, clinical evidence, and emerging nanotechnology-enabled delivery approaches, emphasising rational formulation design and translational considerations necessary for advancing CBs toward standardised and clinically reliable dermatological therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/42076122

“In summary, cannabinoids represent a biologically plausible yet clinically evolving therapeutic class in dermatology. Advancing their role in patient care will depend on coordinated progress in mechanistic understanding, pharmaceutical design, and structured clinical validation.”

https://www.mdpi.com/1999-4923/18/4/469

Pharmacological Insights into Cannabidiol for Wound Healing and Bone Regeneration

“Cannabidiol (CBD), a major nonpsychoactive phytocannabinoid derived from Cannabis sativa L., has recently gained prominence for its broad pharmacological profile and emerging applications in regenerative medicine.

Beyond its well-established neuroprotective, antiepileptic, anxiolytic, antipsychotic, anti-inflammatory, analgesic, and anticancer effects, CBD has demonstrated the capacity to modulate key biological processes involved in tissue repair. Increasing evidence indicates that CBD promotes wound healing by regulating inflammatory responses, cellular proliferation, and extracellular matrix remodeling through interactions with cannabinoid and noncannabinoid receptors expressed in neural, immune, and epithelial cells.

Notably, these receptors are also present in osteogenic and progenitor cells, suggesting that CBD may influence bone metabolism and regeneration. Recent preclinical studies have reported that CBD enhances osteoblastic differentiation, angiogenesis, and matrix mineralization, highlighting its potential as a bioactive molecule for bone tissue engineering.

Within the dental field, such properties open new perspectives for the development of CBD-based biomaterials aimed at improving osseointegration, soft tissue healing, and the overall biological performance of implantable devices.

Accordingly, this review aims to provide a comprehensive overview of the pharmacological and molecular mechanisms underlying the effects of CBD on wound healing and bone regeneration. Furthermore, it discusses dose-response relationships, delivery routes, formulation strategies, and the current legal and regulatory frameworks influencing CBD translation into clinical dental applications.

These insights may support the rational design of next-generation bioactive materials incorporating CBD for oral and maxillofacial regenerative therapies.”

https://pubmed.ncbi.nlm.nih.gov/42077915

“In conclusion, this critical review examined the biological mechanisms through which cannabidiol (CBD) may contribute to wound healing and bone repair/regeneration. Current preclinical evidence supports the therapeutic potential of CBD in enhancing both soft- and hard-tissue repair by modulating key molecular pathways involved in inflammation, cellular proliferation, angiogenesis, and extracellular matrix remodeling.”

https://pubs.acs.org/doi/10.1021/acsomega.5c13259

Comprehensive two-dimensional liquid chromatographic analysis of Cannabis phenolics and first evidence of flavoalkaloids in Cannabis

“Cannabis contains a large number of diverse metabolites. Compared to the well-studied cannabinoids and terpenoids, characterization of the phenolic composition of Cannabis has received little attention. With studies reporting synergistic effects in Cannabis, the importance of investigating polyphenols in Cannabis is becoming more apparent.

We report an on-line comprehensive 2D HILIC × RP-LC method hyphenated to high resolution (HR) MS for the detailed characterization of polar phenolics in Cannabis inflorescence and leaf samples of three commercial strains. Optimal HILIC × RP-LC conditions were derived using an automated method optimization program, and provided excellent separation performance (peak capacity > 3000) and high orthogonality. Diode array and HR-MS data enabled tentative identification of 79 compounds, comprising mainly flavone and (hydroxy)cinnamic acid derivatives. Compound assignment was facilitated by the group-type separation obtained between the phenolic acids and flavonoids, as well as the structured elution patterns for the flavone glycosides.

The presence of three C-glycosylated flavones, as well as several of their O-glycosylated derivatives, distinguished one of the strains from the other two. In the same strain, flavoalkaloids were detected, mainly in the leaf extracts.

The structures of the alkaloid moieties could not be unambiguously assigned based on the available HR-MS data, but four classes of flavoalkaloids comprising 16 flavone derivates could be tentatively identified.

This is the first time that this relatively rare and chemically interesting class of compounds has been detected in Cannabis.

These findings highlight the diversity of Cannabis, and the utility of HILIC × RP-LC-HR-MS for the in-depth study of its phenolic composition.”

https://pubmed.ncbi.nlm.nih.gov/40359741

Cannabis is a herbaceous plant of the Cannabaceae family originating from Western Asia, that has been cultivated across the world for many purposes ranging from textile to medicinal uses for more than six millennia “

https://www.sciencedirect.com/science/article/pii/S0021967325003711?via%3Dihub

“Don’t toss cannabis leaves: Scientists found rare compounds with medical potential. Cannabis just revealed a hidden chemical treasure—rare compounds scientists never knew were there.” https://www.sciencedaily.com/releases/2026/05/260501002156.htm

Immunohistochemical analysis and distribution of lymphocytes and Kupffer cells in the liver of rats with long-term experimental use of hemp seed oil

Objective: Aim: To conduct histological and immunohistochemical analysis and distribution of lymphocytes and Kupffer cells in the liver of rats with long-term experimental use of hemp seed oil (HSO).

Patients and methods: Materials and Methods: 26 sexually mature male rats (180-230 g, 5-7 months old) were divided into three groups: experimental (n=14, 0.5 ml/kg/day HSO orally for 10 weeks), control (n=6, 0.1 ml/kg/day HSO orally for 10 weeks), and intact (n=6). Histological and immunohistochemical (CD3, CD20, CD56, CD68) studies, alongside quantitative analysis of lymphocyte and macrophage distribution in hepatic lobules, were performed. Statistical significance was assessed using Mann-Whitney and Pearson tests, with p<0.05 considered significant.

Results: Results: After 10 weeks of 0.5 ml/kg/day HSO, 71.43% of experimental rats developed mild fatty liver disease (Kleiner grade S1 steatosis), a significant difference from the control group (p<0.0001). No histological inflammation or necrotic changes in hepatocytes were observed. Small numbers of CD3 lymphocytes were present in portal tracts, without extending into or damaging the adjacent parenchyma. CD20 and NK resident lymphocytes were sparse. Aggregates of CD68-positive Kupffer cells were most common near liver lobule triads. The average number of Kupffer cells (5.79±0.06 per 0.01 mm2) in the experimental group significantly (p<0.001) exceeded the control by 1.49 times, suggesting hyperplasia of specialized macrophages and their increased role in liver immune function.

Conclusion: Conclusions: Ten weeks of experimental use indicates that hemp seed oil is safe to consume at a dose of 0.5 ml/kg/day.”

https://pubmed.ncbi.nlm.nih.gov/42048501

Associations of Low-Level Prenatal Alcohol and Cannabis Exposure With Adolescent Cognitive Trajectories

Background: No studies have examined the differential and combined effects of prenatal alcohol and cannabis exposure (PAE/PCE) on longitudinal trajectories of adolescent cognitive development. Further, previous alcohol research is mixed, with some evidence for negative PAE effects on cognition and other studies reporting null or positive associations. This study examined associations between PAE, PCE, and growth trajectories of adolescent cognition in a large, diverse sample.

Methods: N = 11,029 adolescents from the Adolescent Brain Cognitive Development℠ Study completed the NIH Toolbox cognitive battery at baseline (Mage = 9.95), two-year follow-up (Mage = 11.95), and four-year follow-up (Mage = 14.07). Retrospective parent report of PAE and PCE was assessed at baseline. Univariate growth trajectories were estimated for cognitive measures: Pattern Comparison, Picture Sequence Memory, Oral Reading, Flanker Task, and Picture Vocabulary. Cross-product terms for PAE and PCE tested combined use.

Results: Most mothers reported no prenatal alcohol (n = 8257; 74%) or cannabis (n = 10,812; 94%) use. Overall, use was low: across pregnancy, women reporting any alcohol use averaged 33.31 drinks, and those reporting any cannabis use averaged 33.00 use occasions. Before including covariates, there were negative main effects of PCE and positive main effects of PAE on intercepts for all five cognitive domains. There was little evidence for PCE/PAE effects on slopes for cognition. After adding covariates, no negative effects of PCE remained. Small positive PAE effects on intercepts for multiple domains persisted. Cross-product terms for combined exposure were not significant.

Conclusions: Little evidence emerged for negative effects of low PAE, PCE, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors. Light drinking in families with social features positively associated with cognitive ability may result in few negative consequences. This study is the first to demonstrate weak evidence for adverse differential and combined low-level PAE and PCE effects on the development of adolescent cognition.”

https://pubmed.ncbi.nlm.nih.gov/41947378

“Little evidence emerged for negative effects of low level prenatal alcohol, cannabis, or combined exposure on adolescents’ cognitive development after accounting for sociodemographic factors.”

https://onlinelibrary.wiley.com/doi/10.1111/acer.70297

Inhibitory effect of cannabidiol on infectious bronchitis virus in chickens in vitro and in vivo

“Avian infectious bronchitis virus (IBV), a gamma coronavirus, remains the predominant pathogen affecting poultry worldwide, posing a significant threat to the poultry industry.

Cannabidiol (CBD), the primary non-psychoactive constituent of Cannabis sativa, has demonstrated diverse pharmacological properties.

This study investigated the inhibitory effects of CBD against IBV infection both in vitro and in vivo. Chicken embryo kidney (CEK) cells infected with IBV were treated with CBD at various concentrations (2–20 µM).

Our results demonstrated that CBD significantly suppressed IBV replication in a dose-dependent manner without affecting cell viability. Furthermore, in SPF chickens, CBD treatment markedly alleviated clinical symptoms, reduced tracheal and renal histopathological lesions, and significantly decreased viral loads in tissues. Transcriptomic analysis of tracheal tissue suggested that CBD may inhibit IBV infection through modulation of immune-related signaling pathways, particularly the JAK-STAT pathway and interferon-stimulated gene expression.

These findings indicate that CBD represents a promising candidate for therapeutic intervention against IBV infection.”

https://link.springer.com/article/10.1007/s00203-026-04886-7

Exploring the therapeutic potential of cannabidiol in soft tissue wound healing: Delivery strategies and anti-inflammatory pathways

“This review explores the molecular and cellular pathways of soft tissue wound healing and the potential therapeutic use of the non-psychotropic cannabinoid cannabidiol (CBD), integrating findings from in vitro and in vivo preclinical studies as well as completed and ongoing clinical trials.

It provides a comprehensive summary of the next steps in new CBD-based product development by analyzing current trends in dosage optimization, treatment guidance, delivery systems, ranging from liposomes, microemulsions to hydrogels. Additionally, the review examines clinical trials related to CBD formulations, delivery routes, and participant outcomes, offering a deeper understanding of the mechanisms guiding the activity beyond binding to cannabinoid 1 (CB1) and CB2 receptors. Furthermore, it highlights challenges and future perspectives in CBD formulation studies, presenting both currently studied approaches and emerging possibilities for innovation.

Therapeutic potential of CBD has proved itself in the recent years and only regulatory issues and clarity in treatment and delivery routes will limit its widespread use in soft tissue healing.”

https://pubmed.ncbi.nlm.nih.gov/42039297

“The therapeutic properties of Cannabis sativa have been recognized for over five millennia, with it use as a medical substance dating back to the Christian era in Central and Northeast Asia, particularly in India. However, despite its potential, this plant has undergone limited scientific exploration of its chemical and biological properties, and its medical use has remained restricted, particularly following its classification as a substance with no medical value under the United Nations Single Convention on Narcotic Drugs.”

“The historical use of cannabinoids in ancient medicine, coupled with modern preclinical investigations into their various components, unveils a broad spectrum of its potential clinical applications for soft tissue regeneration.”

“The unique therapeutic properties of CBD hold great promise for the treatment of different diseases and disorders, including alleviating pain associated with various soft tissue injuries or conditions, fibrosis, inflammation, and addressing muscle disorders.”

https://www.sciencedirect.com/science/article/pii/S2211383525006744?via%3Dihub

The greater the pleiotropic effects, the greater the benefits – cannabis as a “biopsychosocial” drug: a mixed-methods study on chronic non-cancer pain

Background: Against the background of widely inconsistent data from randomized controlled trials (RCT), the use of cannabis-based medicines (CBM) from the perspective of patients with chronic non-cancer pain (CNCP) was described.

Methods: Based on a purposive/convenient sampling, patients were recruited from the Pain Clinic of Hannover Medical School who had been using CBM prescribed by a doctor for at least 6 months. The patients discussed their experiences with CBM in semi-structured individual interviews. The interview transcripts were coded and analyzed using a modified grounded theory approach with the help of MAXQDA®. In addition, the Treatment Satisfaction Questionnaire with Medication (TSQM) was used.

Results: Theoretical saturation was reached after 32 interviews. Open and selective coding revealed the overarching phenomenon of “subjective pain experience under CBM therapy”, with one of the main themes being the “effect of CBM”. This revealed the categories “effect on pain” and “psychological” and “somatic effect”. The most important concepts were “pain intensity”, “pain management”, “stress management”, “musculoskeletal system”, and “sleep quality.” Constructing a theoretical framework 4 groups of responses to CBM treatment were identified. The focus is either on (I) pain reduction, (II) pain coping, (III) reduced stress or (IV) multidimensional aspects. When this classification was applied to topic of quality of life (QOL), the greatest effectiveness and highest overall satisfaction were found in group (IV). Mixed methods showed a continuous increase in the perceived effectiveness of CBM on pain-centered complaints from group (I) to (IV).

Conclusions: In line with the biopsychosocial understanding of chronic pain, it appears that those CNCP patients who benefit most from CBM are those who show the most far-reaching effects on both a physical and psychological level. The pleiotropic effects of CBM may be responsible for this. Based on these results, interdisciplinary prospective research appears sensible and necessary to further and systematically investigate this clinically relevant topic.”

https://pubmed.ncbi.nlm.nih.gov/42015327

https://link.springer.com/article/10.1186/s42238-026-00440-w

Prenylated apigenin derivatives from Cannabis sativa L.: isolation, biosynthesis, and anti-inflammatory properties

Background: Cannabis sativa L. accumulates a wide array of specialized compounds, many of which are non-psychotropic and show significant promise in medical and therapeutic applications. One such group of C. sativa compounds is prenylated flavonoids, which have emerged as potential treatments for chronic pain and inflammation. Accordingly, the aim of this study was to isolate, identify, and synthesize prenylated flavonoids from C. sativa and test their efficacy as anti-inflammatory agents.

Methods: An enriched polyphenol extract from C. sativa was fractionated using flash chromatography and high-performance liquid chromatography to isolate prenylated flavonoids. Liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy were employed to determine their structures. Phylogenomic and classical biochemical approaches were combined to identify the enzyme involved in the biosynthesis of the isolated compounds. Finally, these prenylated flavonoids were tested to determine their inhibitory properties against microsomal prostaglandin E synthase-1 (mPGES-1) activity.

Results: Two prenylated flavonoids were isolated from the aerial parts of the C. sativa plant using classical chromatographic procedures and identified as 6-prenylapigenin (6-PA) and 6-geranylapigenin (6-GA). A C. sativa prenyltransferase (CsPT3) from the UbiA superfamily was identified to complete the final prenylation step in 6-PA and 6-GA biosynthesis from the widespread plant flavonoid known as apigenin. The inhibitory potentials of 6-PA and 6-GA against mPGES-1 activity were approximately as effective as, or better than, that of a leading commercially available inhibitor, MK-886. Molecular docking simulations confirmed strong binding affinities of 6-PA and 6-GA to mPGES-1 compared to its natural substrate.

Conclusions: 6-PA and 6-GA are prenylated derivatives of the widespread plant flavonoid known as apigenin. These non-psychotropic flavonoids accumulate in C. sativa and exhibit potent inhibition of mPGES-1, a chief mediator in the pro-inflammatory pathway. Identification of the final step in 6-PA and 6-GA biosynthesis, together with their now-established anti-inflammatory activity, presents propitious biotechnological avenues for these therapeutically relevant C. sativa compounds.”

https://pubmed.ncbi.nlm.nih.gov/41987337

https://link.springer.com/article/10.1186/s42238-026-00438-4

“Apigenin: A Promising Molecule for Cancer Prevention”

https://pmc.ncbi.nlm.nih.gov/articles/PMC2874462

“Apigenin: A Bioflavonoid with a Promising Role in Disease Prevention and Treatment”

https://pmc.ncbi.nlm.nih.gov/articles/PMC11202028

Phenolic Constituents Drive Antimicrobial and Antibiotic-Enhancing Activities of Cannabis sativa Seed Extracts Obtained by Two Extraction Methods

“Hemp seeds (Cannabis sativa L.) are a rich source of phenolic compounds with antioxidant and antimicrobial potential.

Still, their genotype-dependent variability and ability to enhance antibiotic efficacy remain insufficiently explored. This study compared three Romanian hemp seed cultivars (Lovrin 110, Silvana, and LV 585) extracted by conventional hydroalcoholic extraction (CE) and ultrasound-assisted extraction (UAE) to evaluate their phenolic composition, antimicrobial effects, and synergistic interactions with amoxicillin and miconazole.

HPLC identified genotype- and method-dependent differences, with UAE extracts showing substantially higher levels of epicatechin, quercetin, rosmarinic acid, resveratrol, and ferulic acid. These patterns showed stronger antimicrobial inhibition against Gram-positive and Gram-negative bacteria and yeasts, confirmed by MIC, fold-reduction, and percent enhancement assays. The most pronounced synergy occurred in Streptococcus pyogenesStaphylococcus aureusBacillus cereus, and Candida albicans. PCA revealed two dominant phenolic-activity axes: a rosmarinic/resveratrol/ferulic axis associated with potent inhibition in Escherichia coli and C. albicans, and a quercetin-driven axis linked to Gram-positive bacteria.

Overall, UAE extracts displayed superior phenolic enrichment and bioactivity, demonstrating that specific phenolic structures-not total phenolic content-govern antimicrobial performance and antibiotic-enhancing potential in hemp seed extracts.”

https://pubmed.ncbi.nlm.nih.gov/41514973

Cannabis sativa L. (hemp) is an herbaceous, anemophilous species in the Cannabaceae family. It is considered one of the oldest domesticated crops. Due to its long history of use, it is now seen as a versatile, sustainable crop with a relatively low environmental impact and significance across sectors such as agriculture, phytoremediation, food and feed production, cosmetics, construction materials, and pharmaceuticals.”

“Hemp seed has historically served as a medicinal resource, used to address a range of conditions such as arthritis, asthma, menstrual discomfort, atopic dermatitis, cancer, hypertension, and other inflammatory diseases.”

“These findings identify hemp seeds—particularly when extracted by UAE—as promising natural antimicrobial agents and effective adjuvants for conventional antibiotics and antifungals.”

https://www.mdpi.com/2223-7747/15/1/27