Search Results (195)

The endocannabinoid system (ECS) is a complex neuromodulatory network involved in maintaining physiological balance through interactions with various neurotransmitter and hormonal pathways. Its key components—cannabinoid receptors (CBRs)—are activated by endogenous ligands and exogenous cannabinoids such as those found in the Cannabis sativa plant. Although cannabinoids like cannabidiol (CBD) have garnered interest for their potential therapeutic effects, evidence regarding their safety, particularly for reproductive health, remains limited. This review summarizes the structure and molecular mechanisms of the ECS, its role in reproductive physiology—including its interactions with the hypothalamic–pituitary–gonadal axis (HPG axis), gametogenesis, implantation, and lactation—and the possible consequences of cannabinoid exposure for fertility. In addition, we focus on the involvement of the ECS and cannabinoids in breast cancer, highlighting emerging evidence on their dual role in tumor progression and therapy. These insights emphasize the need for further research to better define the therapeutic potential and risks associated with cannabinoid use in reproductive health and breast cancer. Full article

Cannabinoid hyperemesis syndrome (CHS) is characterized by a pattern of cyclic vomiting and abdominal pain despite an absence of an organic cause, occurring in regular cannabis users. This syndrome was first described in 2004. Initially considered rare, with the increased use and legalization of cannabis, a growing incidence of diagnoses has been observed. Data on the pediatric population are still scant despite the high rate of cannabis consumption in young people. In this narrative review, we aim to synthesize the growing knowledge about CHS and its epidemiology, pathophysiology, diagnosis, and management in the pediatric population. Findings in this review highlight the diagnostic challenges in pediatric patients, the limited efficacy of standard anti-emetic therapies, and the central role of cannabis cessation in treatment. This review underscores the need for increased awareness of CHS in pediatric practice to ensure timely diagnosis and avoid unnecessary investigations and interventions. Full article

Many neurodegenerative diseases are associated with immune system disorders, while neurodegenerative processes often occur in inflammatory conditions of the Central Nervous System (CNS). Cannabinoids exhibit significant therapeutic potential due to their dual ability to modulate both neural and immune functions. These compounds have a broad spectrum of action, allowing them to target multiple pathological mechanisms underlying neurodegenerative and inflammatory CNS diseases. The present review outlines the therapeutic potential of cannabinoids, with a focus on their anti-inflammatory properties, in the treatment of neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease, as well as inflammatory CNS disorders like multiple sclerosis and HIV-associated dementia. Full article

Epilepsy affects over 12 million children worldwide, with approximately 30% classified as having drug-resistant epilepsy (DRE), often accompanied by neuropsychiatric comorbidities that severely impact quality of life. The endocannabinoid system (ECS) functions as a multifaceted neuromodulatory network regulating neuronal excitability, synaptic plasticity, and immune homeostasis from early life through adolescence and into aging. In pediatric epilepsies, alterations in ECS components, particularly CB1 receptor expression and endocannabinoid levels, reveal disorder-specific vulnerabilities and therapeutic opportunities. Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa, has shown strong preclinical and clinical efficacy in treating DRE and is approved for Dravet syndrome, Lennox–Gastaut syndrome, and Tuberous Sclerosis Complex. Other ECS-based strategies, such as the use of CB1 receptor-positive allosteric modulators, can selectively enhance endogenous cannabinoid signaling where and when it is active, potentially reducing seizures in conditions like Dravet and absence epilepsy. Similarly, FAAH and MAGL inhibitors may help restore ECS tone without directly activating CB1 receptors. Precision targeting of ECS components based on regional expression and syndrome-specific pathophysiology may optimize seizure control and associated comorbidities. Nonetheless, long-term pediatric use must be approached with caution, given the critical role of the ECS in brain development. Full article

Recent advances in cannabinoid-based therapies identified the natural CB2 receptor agonist β-caryophyllene (BCP) as a promising anti-inflammatory and neuroprotective agent. To further explore its therapeutic potential on the management of neurodegenerative disorders, in the present study we investigated the ability of BCP to prevent neuroinflammation and promote neuroprotection by using both in vitro and ex vivo models of β-amyloid induced neurotoxicity. Our data showed that BCP significantly protected human microglial HMC3 cells from Aβ_25-35-induced cytotoxicity, reducing the release of pro-inflammatory cytokines (TNF-α, IL-6) while enhancing IL-10 secretion. These effects were associated with a reduced activation of the NF-κB pathway, which emerged as a central mediator of BCP action. Notably, the use of CB2R- or PPARγ-selective antagonists revealed that the observed NF-κB inhibition by BCP may involve the coordinated activation of both canonical (e.g., CB2R) and non-canonical (e.g., PPARγ) receptors. Moreover, BCP restored the expression of SIRT1, PGC-1α, and BDNF, indicating the involvement of neurotrophic pathways. Clear neuroprotective properties for BCP have been highlighted in Aβ_1-42-treated brain slice preparations, where BCP demonstrated the rescue of both the amyloid-dependent depression of BDNF expression and long-term synaptic potentiation (LTP) impairment. Overall, our results suggest that BCP constitutes an attractive natural molecule for the treatment of Aβ-induced neuroinflammation and synaptic dysfunction, warranting further exploration for its clinical application. Full article

Background: Cannabidiol (CBD), a non-intoxicating phytocannabinoid, has garnered interest as a potential therapeutic agent for managing pain and inflammation associated with upper-quarter disorders, including temporomandibular disorders (TMDs), orofacial pain, myofascial dysfunction, and postoperative dental pain. Methods: This systematic review critically evaluated clinical, preclinical, and mechanistic studies on the efficacy and safety of CBD in the management of such conditions. A total of 10 studies, comprising randomized clinical trials and animal models, met the inclusion criteria and were assessed for methodological quality and risk of bias. Results: The findings suggest that CBD demonstrates analgesic, anti-inflammatory, and muscle-relaxant effects in chronic myofascial TMDs and bruxism, particularly when applied topically or intraorally. In contrast, studies on acute nociceptive pain (e.g., pulpitis, third molar surgery) yielded inconsistent results. Notably, CBD enhanced the effects of conventional analgesics such as opioids and NSAIDs in several preclinical models, indicating synergistic potential. However, substantial heterogeneity in CBD dosage, formulation, administration routes, and outcome measures limited comparability across studies. Adverse effects were minimal in clinical trials, yet underreported. Conclusions: While early evidence supports CBD’s potential as an adjunctive treatment for certain upper-quarter conditions, especially those involving chronic myofascial pain, further high-quality, condition-specific trials are required to establish standardized dosing, delivery methods, and long-term safety. Full article

Neuropathic pain resulting from injury to the somatosensory nervous system affects approximately 6.9–10% of the general population and significantly impacts quality of life. Common presentations include burning, stabbing, tingling, or electrical sensations, occurring spontaneously or through hyperalgesia or allodynia. Treatment approaches follow a tiered system. First-line therapies include gabapentinoids (e.g., gabapentin, pregabalin), which target voltage-gated calcium channels; tricyclic antidepressants (e.g., amitriptyline, nortriptyline); and serotonin-norepinephrine reuptake inhibitors such as duloxetine. Second-line options encompass topical agents (e.g., 5% lidocaine, 8% capsaicin), opioid-like medications (e.g., tramadol, tapentadol), and adjunctive therapies including psychological therapies and lifestyle interventions. For refractory cases, third-line treatments include NMDA receptor antagonists (e.g., ketamine, dextromethorphan), cannabinoids, and botulinum toxin type A, though these have more limited clinical evidence. Procedural interventions such as spinal cord stimulation and transcutaneous electrical nerve stimulation provide alternatives when pharmacological approaches fail. Despite advances in treatment options, many patients remain undertreated, highlighting the need for individualized, multimodal approaches and continued research into the complex pathophysiology of neuropathic pain conditions. Full article

Posttraumatic stress disorder is often treatment-resistant and recent research has suggested that treatment outcomes might be improved by modulation of the endocannabinoid system. The current review article describes animal and human research examining the effect of endocannabinoid modulation on posttraumatic symptoms, behaviours, and relevant memory processes. While the preclinical literature is reasonably consistent, emerging human literature is mixed. This review explores some potential reasons for why human research in this field is inconsistent and proposes multiple avenues for future research to answer these questions. Clinical trials testing the logistical challenges of cannabinoid administration and carefully designed human experimental studies are urgently required before cannabinoid therapy can be considered as an approach for treatment of posttraumatic stress disorder. Full article

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

Oral infections, caused by bacterial, fungal, and viral pathogens, are a significant source of dental morbidity and can lead to systemic complications, especially in immunocompromised individuals. Complex microbial interactions and host immune responses drive common conditions such as dental caries, periodontal disease, oral candidiasis, and herpetic lesions. Conventional antimicrobial therapies face limitations due to resistance and adverse effects, prompting interest in alternative treatments. Cannabidiol (CBD), a non-psychoactive compound derived from Cannabis sativa, has emerged as a promising candidate due to its antimicrobial, anti-inflammatory, and immunomodulatory properties. CBD targets various molecular pathways, including cannabinoid receptors, TRP channels, adenosine receptors, and PPARs, contributing to its multifaceted therapeutic effects. It has demonstrated efficacy against oral pathogens such as Streptococcus mutans, Enterococcus faecalis, and Candida albicans, disrupting biofilms and bacterial membranes. Additionally, CBD modulates inflammatory responses by reducing cytokine production and oxidative stress, particularly relevant in chronic conditions like periodontal disease. Emerging evidence also suggests synergistic effects with conventional antimicrobials and benefits in tissue regeneration. This review highlights the therapeutic potential of CBD in managing oral infections, offering a novel approach to overcoming current treatment limitations and guiding future research into safer and more effective oral health interventions. Full article

Cannabidiol (CBD) has shown promise in treating cancers with an inflammatory microenvironment. Although it has been demonstrated that IL-1β induces epithelial-mesenchymal transition (EMT) of MCF-7 cells and CBD reverts this process, in restoring the epithelial non-invasive phenotype, there is limited understanding of how this cannabinoid regulates these processes. In this work, MCF-7 cells were induced to adopt an aggressive phenotype (6D cells), which was reversed by CBD. Then, protein expression was analyzed by mass spectrometry to compare 6D vs. MCF-7 cells and 6D+CBD vs. 6D cells proteomes. Novel proteins associated with EMT and CBD signaling were identified. Twenty-four of them were oppositely regulated by IL-1β and CBD, suggesting new points of crosstalk between the IL-1β and CBD signaling pathways. From the data, two protein networks were constructed: one related to EMT with 58 up-regulated proteins and another with 21 related to CBD signaling. The first one showed the proteins BRCA1, MSN, and CORO1A as the key axis that contributes to the establishment of a mesenchymal phenotype. In the CBD signaling, the key axis was formed by SUPT16H, SETD2, and H2BC12, which suggests epigenetic regulation by CBD in the restoration of an epithelial phenotype of breast cancer cells, providing new targets for anticancer therapy. Full article

Glioblastoma (GBM), a devastating brain malignancy, resists conventional therapies due to molecular heterogeneity and the blood–brain barrier’s significant restriction on drug delivery. Cannabinoids like WIN 55,212-2 show promise but are limited by poor solubility and systemic toxicity. To address these challenges, we evaluated styrene–maleic acid (SMA) micellar encapsulation of WIN 55,212-2 (SMA-WIN) against free WIN in epithelial (LN18) and mesenchymal (A172) GBM cell lines, targeting cytotoxicity and receptor modulation (CB1, CB2, TRPV1, PPAR-γ). SMA-WIN exhibited significantly enhanced cytotoxicity, achieving IC50 values of 12.48 µM (LN18) and 16.72 µM (A172) compared to 20.97 µM and 30.9 µM for free WIN, suggesting improved cellular uptake via micellar delivery. In LN18 cells, both formulations upregulated CB1 and CB2, promoting apoptosis. Notably, SMA-WIN uniquely increased PPAR-γ expression by 2.3-fold in A172 cells, revealing a mesenchymal-specific mechanism absent in free WIN, which primarily modulated CB1/CB2. These findings position SMA-WIN as a promising candidate for precision GBM therapy, particularly for resistant mesenchymal subtypes, paving the way for in vivo validation to confirm blood–brain barrier penetration and clinical translation. Full article

Cell-based therapy using mesenchymal stem cells (MSCs) shows promise for treating several diseases due to their anti-inflammatory and immunomodulatory properties. To enhance the therapeutic potential of MSCs, in vitro priming strategies have been explored. Cannabidiol (CBD), a non-psychoactive compound derived from cannabis, may influence MSC proliferation, differentiation, and immunomodulatory properties. This study evaluates the immunomodulatory potential of equine adipose tissue-derived MSCs (EqAT-MSCs) primed with a CBD-rich cannabis extract. EqAT-MSCs (P3) were primed with CBD concentrations of 5 µM and 7 µM for 24 h. Morphological analysis, MTT assay, β-galactosidase activity, apoptosis assays, and gene expression of interleukins IL-1β, IL-6, IL-10, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) were conducted. Additionally, cannabinoid receptor 1 (CB1) and 2 (CB2) expression were evaluated in naïve EqAT-MSCs (P2–P5). The naïve EqAT-MSCs expressed CB1 and CB2 receptors. Priming with 5 µM significantly increased the expression of IL-10, TNF-α, and IFN-γ, while 7 µM decreased IL-1β and IL-6 expression. No significant changes were observed in other cytokines, MTT, β-galactosidase activity, or apoptosis. These findings demonstrate that naïve EqAT-MSCs express CB1 and CB2 receptors and priming with the extract modulates the expression of pro- and anti-inflammatory cytokines, highlighting its potential immunomodulatory role in EqAT-MSC-based therapies. Full article

Background: Agitation is a frequent and challenging symptom in schizophrenia and bipolar disorder, characterized by heightened motor activity, emotional distress, and potential aggression. This symptom is most observed during acute episodes, representing a significant burden on patients, caregivers, and healthcare systems. Agitation is a leading cause of emergency department visits and psychiatric hospitalizations, necessitating prompt and effective interventions to ensure safety and mitigate its far-reaching impact. Traditional treatments, including high-potency antipsychotics and benzodiazepines, remain first-line options but are associated with significant drawbacks such as sedation, extrapyramidal symptoms, tolerance, and limited applicability in certain patient populations, especially those with respiratory or cardiac depression and the elderly. Non-pharmacologic strategies like de-escalation techniques and environmental modifications are invaluable but may be impractical in acute care settings, as speed and efficiency are critical in emergent settings. These limitations, including the onset of extrapyramidal symptoms with high-dose antipsychotics and the development of tolerance with benzodiazepines, highlight gaps in care, including the need for faster-acting, safer, and more patient-friendly alternatives that reduce reliance on physical restraints and invasive interventions. Methods: This review explores the evolution of treatments for agitation, focusing on alternative and innovative approaches. To highlight these treatments, an extensive review of the literature was conducted utilizing PubMed, Google Scholar, Embase.com, and other search engines. Results: Key developments include sublingual dexmedetomidine, recently FDA-approved, which offers sedation without respiratory depression and a non-invasive administration route. Similarly, subcutaneous olanzapine provides a more convenient alternative to intramuscular injections, reducing injection-related complications. Other emerging treatments such as gabapentin, pregabalin, and ketamine show promise in addressing agitation in specific contexts, including comorbid conditions and treatment-resistant cases. A comparative analysis of these therapies highlights their mechanisms of action, clinical evidence, and practical challenges. Conclusions: Future directions emphasize intranasal delivery systems, novel pharmacologic agents, and potential roles for cannabinoids in managing agitation. These innovations aim to balance rapid symptom control with improved patient safety and experience. The set back with these emerging techniques is a lack of standardized dosing and protocols. They also face ethical concerns, including the chance of misuse or abuse, as well as regulatory barriers, as they lack FDA approval and their legality changes between states. This review underscores the clinical, practical, and ethical considerations in advancing care for agitated patients, paving the way for more effective and compassionate management strategies in psychiatric settings. Full article

Background/Objectives: Head and neck cancer is one of the most common cancers globally, with high mortality and significant treatment-related side effects. Conventional therapies, including surgery, radiotherapy, and chemotherapy, have improved survival but often have serious consequences for patients’ quality of life. For this reason, there is growing interest in complementary therapies such as acupuncture, herbal medicine, cannabinoids, traditional Chinese medicine, and mind-body therapies. Methods: This review was conducted through a systematic analysis of the scientific literature available on PubMed and Scopus, selecting studies about the use of alternative therapies in patients with head and neck cancer according to strict criteria. Results: Acupuncture has shown benefits in the management of xerostomia and dysphagia, while some herbal medicines have shown potential anticancer effects, although with limitations related to bioavailability. Vitamins and antioxidants showed mixed results: some studies suggest a protective effect, while others report a possible increased risk of cancer progression. Cannabinoids are a controversial topic, with possible palliative benefits but also a higher risk of head and neck cancer. Traditional Chinese medicine and mind-body therapies, such as yoga, have shown positive effects on patients’ well-being, although their direct impact on cancer progression remains uncertain. Conclusions: Alternative therapies could be a useful support in managing symptoms and improving the quality of life patients with head and neck cancer. However, solid scientific evidence on their effectiveness and safety is still lacking. Rigorous clinical studies are needed to assess their therapeutic potential and define a safe integration into multidisciplinary cancer management. Full article