Therapeutic Potential for Cannabis and Cannabinoids, 3rd Edition

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 1267

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Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, USA
Interests: cannabis; cancer; inflammatory bowel disease; pain; cannabinoids
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Special Issue Information

Dear Colleagues,

Cannabis has a history of medical use dating back millennia; however, the use of cannabis for medicinal purposes fell out of favor in the last century. There is currently a renewed interest in the potential medicinal value of this plant, as well as individual compounds produced by Cannabis (and synthetic analogs). Currently, nearly 50 countries permit the medical use of cannabis, and over a dozen other countries have legalized cannabis-based products (CBD, Sativex, Dronabinol, etc.) for medical use. While there exists a plethora of anecdotal reports demonstrating that cannabis can treat a variety of diseases, there is a limited number of strong, evidence-based scientific data supporting these claims.

This Special Issue of Biomedicines, “Therapeutic Potential for Cannabis and Cannabinoids”, will be dedicated to providing evidence for the medicinal value of cannabis in treating human illness and disease. Topics will include but are not limited to preclinical animal models examining the efficacy of cannabis and cannabinoid derivatives on pain, anxiety, cancer, and other diseases and cell and molecular models of cannabinoid pharmacokinetics, drug–drug interactions, and disease treatment. These studies will be of great importance not only for progressing the cannabis field but also for validating the use of cannabis and cannabinoids as therapeutics.

Dr. Wesley M. Raup-Konsavage
Guest Editor

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Keywords

  • cannabis
  • tetrahydrocannabinols (THC)
  • cannabidiol (CBD)
  • cannabigerol (CBG)
  • cannabinoid
  • cannabinol (CBN)
  • cannabichromene (CBC)
  • pain
  • cancer
  • anxiety
  • PTSD
  • sleep disorders
  • neuroprotection
  • anti-inflammatory

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Published Papers (2 papers)

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25 pages, 4600 KiB  
Article
Cannabidiol-Loaded Retinal Organoid-Derived Extracellular Vesicles Protect Oxidatively Stressed ARPE-19 Cells
by Peggy Arthur, Sangeetha Kandoi, Anil Kalvala, Breana Boirie, Aakash Nathani, Mounika Aare, Santanu Bhattacharya, Tanmay Kulkarni, Li Sun, Deepak A. Lamba, Yan Li and Mandip Singh
Biomedicines 2025, 13(5), 1167; https://doi.org/10.3390/biomedicines13051167 - 10 May 2025
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Abstract
Background/Objectives: Age-related macular degeneration (AMD) is the third leading cause of irreversible blindness in elderly individuals aged over 50 years old. Oxidative stress plays a crucial role in the etiopathogenesis of multifactorial AMD disease. The phospholipid bilayer EVs derived from the culture-conditioned medium [...] Read more.
Background/Objectives: Age-related macular degeneration (AMD) is the third leading cause of irreversible blindness in elderly individuals aged over 50 years old. Oxidative stress plays a crucial role in the etiopathogenesis of multifactorial AMD disease. The phospholipid bilayer EVs derived from the culture-conditioned medium of human induced pluripotent stem cell (hiPSC) differentiated retinal organoids aid in cell-to-cell communication, signaling, and extracellular matrix remodeling. The goal of the current study is to establish and evaluate the encapsulation of a hydrophobic compound, cannabidiol (CBD), into retinal organoid-derived extracellular vesicles (EVs) for potential therapeutic use in AMD. Methods: hiPSC-derived retinal organoid EVs were encapsulated with CBD via sonication (CBD-EVs), and structural features were elucidated using atomic force microscopy, nanoparticle tracking analysis, and small/microRNA (miRNA) sequencing. ARPE-19 cells and oxidative-stressed (H2O2) ARPE-19 cells treated with CBD-EVs were assessed for cytotoxicity, apoptosis (MTT assay), reactive oxygen species (DCFDA), and antioxidant proteins (immunohistochemistry and Western blot). Results: Distinct miRNA cargo were identified in early and late retinal organoid-derived EVs, implicating their roles in retinal development, differentiation, and functionality. The therapeutic effects of CBD-loaded EVs on oxidative-stressed ARPE-19 cells showed greater viability, decreased ROS production, downregulated expression of inflammation- and apoptosis-related proteins, and upregulated expression of antioxidants by Western blot and immunocytochemistry. Conclusions: miRNAs are both prognostic and predictive biomarkers and can be a target for developing therapy since they regulate RPE physiology and diseases. Our findings indicate that CBD-EVs could potentially alleviate the course of AMD by activating the targeted proteins linked to the adenosine monophosphate kinase (AMPK) pathway. Implicating the use of CBD-EVs represents a novel frontline to promote long-term abstinence from drugs and pharmacotherapy development in treating AMD. Full article
(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids, 3rd Edition)
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18 pages, 318 KiB  
Opinion
Palmitoylethanolamide: A Multifunctional Molecule for Neuroprotection, Chronic Pain, and Immune Modulation
by Valeria Di Stefano, Luca Steardo, Jr., Martina D’Angelo, Francesco Monaco and Luca Steardo
Biomedicines 2025, 13(6), 1271; https://doi.org/10.3390/biomedicines13061271 - 22 May 2025
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Abstract
Palmitoylethanolamide (PEA) is an endogenous lipid mediator belonging to the N-acyl-ethanolamine family, widely recognized for its multifaceted effects on neuroprotection, chronic pain management, and immune modulation. As a naturally occurring compound, PEA plays a crucial role in maintaining homeostasis under conditions of cellular [...] Read more.
Palmitoylethanolamide (PEA) is an endogenous lipid mediator belonging to the N-acyl-ethanolamine family, widely recognized for its multifaceted effects on neuroprotection, chronic pain management, and immune modulation. As a naturally occurring compound, PEA plays a crucial role in maintaining homeostasis under conditions of cellular stress and inflammation. Its pharmacological effects are primarily mediated through peroxisome proliferator-activated receptor-alpha (PPAR-α) activation, alongside indirect modulation of cannabinoid receptors CB1 and CB2, as well as interactions with novel targets such as GPR55 and TRPV1. These molecular mechanisms underpin its broad therapeutic potential, particularly in the management of neuroinflammatory and neurodegenerative disorders, pain syndromes, and immune dysregulation. A major advancement in PEA research has been the development of ultramicronized palmitoylethanolamide (umPEA), which significantly enhances its bioavailability and therapeutic efficacy by facilitating better tissue absorption and interaction with key molecular pathways. Preclinical and clinical studies have demonstrated that umPEA is particularly effective in reducing neuroinflammation, stabilizing mast cells, and enhancing endocannabinoid system activity, making it a promising candidate for integrative approaches in neuropsychiatric and chronic inflammatory diseases. Given its well-established safety profile, umPEA represents an attractive alternative or adjunct to conventional anti-inflammatory and analgesic therapies. This communication provides a comprehensive overview of the mechanisms of action and therapeutic applications of both PEA and umPEA, emphasizing their emerging role in clinical practice and personalized medicine. Full article
(This article belongs to the Special Issue Therapeutic Potential for Cannabis and Cannabinoids, 3rd Edition)
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