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Molecular Research on Cannabinoids and Cannabinoid Receptors
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Molecular Research on Cannabinoids and Cannabinoid Receptors

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 25 September 2026 | Viewed by 837

Special Issue Editor

Dr. Valdemiro Amaro Da Silva Junior

E-Mail Website
Guest Editor
Departamento de Medicina Veterinária, Universidade Federal Rural de Pernambuco, Av. Dom Manoel de Medeiros s/n, Dois Irmãos, Recife 52171-900, PE, Brazil
Interests: animal reproduction; experimental pathology; medicinal plant cannabinoids

Special Issue Information

Dear Colleagues,

Cannabinoid research spans from basic neurobiology to clinical trials, focusing on phytocannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), with cannabigerol (CBG) and cannabinol (CBN) as emerging compounds. THC engages CB1 to modulate neurotransmission and analgesia, whereas CBD exerts pleiotropic, non-intoxicating effects. Endocannabinoids anandamide and 2-arachidonoylglycerol fine-tune synaptic plasticity via CB1/CB2. The noncanonical receptors—including GPR55, GPR18, TRPV1/TRPA1 channels, and nuclear PPARs—expand mechanisms to calcium signaling, vasoregulation, metabolism, and gene transcription. Robust evidence supports THC:CBD for spasticity and neuropathic pain and purified CBD for refractory epilepsies, improving quality of life and enabling opioid-sparing strategies. As aging populations and cancer survivorship rise, accessible, standardized cannabinoid medicines may reduce symptom burden and healthcare costs, especially where pain care and mental health resources are scarce. Priorities include receptor mapping, ligand selectivity, PK–PD modeling, real-world pharmacovigilance, and harmonized regulation to ensure safety, equitable access, and rigorous dosing guidance. Integration with biomarkers and omics will refine patient stratification.

Dr. Valdemiro Amaro Da Silva Junior
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • cannabinoids
  • receptors
  • endocannabinoidome
  • degenerative diseases
  • quality of life

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Published Papers (2 papers)

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23 pages, 37504 KB  
Article
Acute Effects of Cannabinoid Combination Therapies in a Western Diet-Induced Murine Model of Metabolic Liver Disease
by Jerome Lian, Mohan Patil, Ricky R. Lareu and Marco Falasca
Int. J. Mol. Sci. 2026, 27(11), 4872; https://doi.org/10.3390/ijms27114872 - 28 May 2026
Viewed by 282
Abstract
Pharmacological treatment of metabolic-dysfunction-associated steatohepatitis remains challenging due to its complex pathophysiology. The endocannabinoidome (eCB) has emerged as a promising therapeutic target given its central role in energy homeostasis and its pharmacological tractability. Western-style diets high in fat and sugar exacerbate metabolic liver [...] Read more.
Pharmacological treatment of metabolic-dysfunction-associated steatohepatitis remains challenging due to its complex pathophysiology. The endocannabinoidome (eCB) has emerged as a promising therapeutic target given its central role in energy homeostasis and its pharmacological tractability. Western-style diets high in fat and sugar exacerbate metabolic liver disease, highlighting the need for effective interventions. Here, we investigated the therapeutic potential of cannabinoid combinations targeting the eCB–liver axis in a Western diet-induced model of metabolic dysfunction. Two weeks of treatment reduced body weight, improved glycaemic control, and ameliorated liver pathology. These effects were accompanied by decreased liver weight, improved liver enzyme profiles, and reduced histological features of steatosis and injury. Overall, these findings suggest that modulation of the eCB system can induce acute improvements in metabolic and hepatic parameters under conditions of diet-induced metabolic stress. These results support further investigation into the eCB system as a therapeutic target, particularly to elucidate underlying mechanisms and longer-term effects. Full article
(This article belongs to the Special Issue Molecular Research on Cannabinoids and Cannabinoid Receptors)
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21 pages, 1296 KB  
Article
Alcohol and Cannabinoids Differentially Regulate Macrophage Polarization, with Co-Exposure Producing an Antagonistic Immunomodulatory Effect
by Esther Penina Shake, Gianelly Vargas Santos and Vijay Sivaraman
Int. J. Mol. Sci. 2026, 27(9), 4054; https://doi.org/10.3390/ijms27094054 - 30 Apr 2026
Viewed by 346
Abstract
Concurrent alcohol and cannabis use (“crossfading”) is increasingly prevalent, especially among adolescents, yet its toxicological impact on pulmonary innate immunity remains largely unexplored. Alveolar macrophages (AMs) orchestrate inflammatory responses in the lung, and dysregulated macrophage polarization is a hallmark of alcohol-associated lung disease. [...] Read more.
Concurrent alcohol and cannabis use (“crossfading”) is increasingly prevalent, especially among adolescents, yet its toxicological impact on pulmonary innate immunity remains largely unexplored. Alveolar macrophages (AMs) orchestrate inflammatory responses in the lung, and dysregulated macrophage polarization is a hallmark of alcohol-associated lung disease. Although alcohol and cannabinoids individually modulate immune function, the mechanisms by which their co-exposure alters macrophage activation and inflammatory signaling in the lung are largely unknown. AMs are highly sensitive to xenobiotic exposure and play a central role in regulating inflammatory and cytotoxic responses. In this study, we investigated how acute ethanol exposure, synthetic cannabinoid exposure, and their combined exposure affect macrophage viability, polarization, and the release of inflammatory mediators via cannabinoid receptor (CB1R/CB2R)-dependent pathways. Human THP-1-derived macrophages and KG-1 macrophage-like cells were exposed to ethanol, the CB1/CB2 agonist WIN 55,212-2, or both, with selective pharmacological antagonism of CB1R and CB2R. Ethanol exposure activated and polarized macrophages toward a pro-inflammatory M1 phenotype, accompanied by increased secretion of pro-inflammatory cytokines MCP-1, TGF-α, IFN-β, IL-6, and TNF-α. In contrast, WIN 55,212-2 promoted anti-inflammatory M2 polarization and increased IL-10 and IL-4 production. Notably, co-exposure to ethanol and WIN produced an antagonistic immunomodulatory response, characterized by the suppression of ethanol-induced M1 polarization and attenuation of pro-inflammatory cytokine release. Mechanistically, pharmacological CB1R blockade reduced ethanol-induced M1 polarization and cytokine secretion, whereas CB2R blockade exacerbated these effects, underscoring divergent roles for cannabinoid receptors in regulating pulmonary macrophage responses. This study provides novel findings demonstrating the mechanism by which alcohol–cannabinoid co-use reshapes macrophage immune phenotypes and identifies the endocannabinoid system as a potential therapeutic target for alcohol-related inflammatory lung disease. Full article
(This article belongs to the Special Issue Molecular Research on Cannabinoids and Cannabinoid Receptors)
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