Cannabis for Chronic Pain: Mechanistic Insights and Therapeutic Challenges

Stresses, Journal Year: 2025, Volume and Issue: 5(1), P. 7 - 7

Published: Jan. 15, 2025

Chronic pain represents a complex and debilitating condition that affects millions of people worldwide, significantly compromising their quality life. The conventional approach to treating this type often relies on the use opioid analgesics anti-inflammatory drugs. While these agents are effective in short term, they present several limitations, including risk dependence, severe side effects, and, some cases, ineffectiveness reducing pain. In context, medical cannabis has emerged as promising therapeutic alternative, given its potential ability relieve effectively with favorable safety profile. This work aims provide comprehensive up-to-date review existing literature effects treatment chronic Cannabis sativa contains pharmacologically active compounds, most prominent which delta-9-tetrahydrocannabinol (∆9-THC) cannabidiol (CBD), interact body’s endocannabinoid system, thereby modulating response. Clinical evidence shown cannabinoids can reduce intensity pain, particularly cases neuropathy, multiple sclerosis, arthritis, other painful conditions unresponsive treatments. However, full integration into clinical practice faces significant obstacles, need for standardized dosing, long-term data, regulatory frameworks. These issues, alongside concerns over adverse drug interactions, must be addressed unlock cannabinoids, patients, who endure both physical suffering added burden stress.

Language: Английский

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Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111350 - 111350

Published: April 1, 2025

Substance use disorder (SUD) is a major global public health challenge, frequently co-occurring with psychiatric conditions such as attention-deficit/hyperactivity (ADHD). Endocannabinoid system (ECS) dysregulation has been implicated in both SUD and ADHD, but the interplay between these remains poorly understood. This study investigates plasma concentrations of endocannabinoid-congeners individuals SUD, without comorbid to identify potential biomarkers. exploratory included 469 participants divided into three groups: (1) healthy controls (n = 136), (2) patients ADHD 267), (3) 66). Plasma 12 endocannabinoid-related molecules, including acylglycerols (2-AG, 2-LG, 2-OG) acylethanolamides (AEA, DEA, DHEA, DGLEA, LEA, OEA, PEA, POEA, SEA), were quantified using high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). A multinomial Elastic Net regression model was applied assess their biomarker potential. Patients exhibited significantly lower 2-AG 2-LG compared controls, while most elevated, except for POEA SEA. comorbidity associated 2-AG, AEA, SEA, PEA elevated. Machine learning analysis identified SEA key biomarkers, achieving an accuracy 72.1 % ROC-AUC 0.77. suggests distinct ECS alterations highlighting Future research should validate findings larger cohorts explore ECS-targeted therapeutic interventions dual-diagnosis populations.

Language: Английский

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Circadian-related Dynamics of the Endocannabinoid System in Male Mouse Brain

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 20, 2025

Abstract Endocannabinoids (eCBs) and related lipids play crucial roles in brain function, including the regulation of circadian rhythms sleep. To comprehensively map these molecules, we employed liquid chromatography high-resolution tandem mass spectrometry (LC/HRMS/MS) to quantify 78 across 14 families seven areas male mice at four time points throughout day (every six hours), during sleep initiation. We found that most eCBs from fatty acids (FAs) family, particularly arachidonic acid (AA), were highly abundant mouse all rhythm. High abundance was shown deeper areas, while temporal differences using Cosinor analysis revealed 26 behaving a rhythm response, with linolenic (LnA) being only lipid show rhythmicity areas. Sleep initiation (ZT1) associated increased N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) activity N-acylethanolamide (NAE) levels cortex hippocampus, wake extension (WEx) altered 2-monoacylglycerol (2-MAG) metabolism cannabinoid receptor 1 (CB1) expression. These findings provide detailed lipidomic brain, highlighting their area-specific distribution, regulation, involvement sleep/wake transitions. Given link between disruption neurodegeneration, future studies should investigate whether observed eCB dysregulation contributes disturbances conditions, if targeting pathways offers novel therapeutic strategies. Significant Statement This comprehensive study provides high-dimensional revealing intricate spatial dynamics role regulating fundamental physiological processes such as

Language: Английский

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Das Sterben des Alters – das Altern des Sterbens

Springer eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 243 - 277

Published: Jan. 1, 2025

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Palmitoylethanolamide: A Multifunctional Molecule for Neuroprotection, Chronic Pain, and Immune Modulation

Biomedicines, Journal Year: 2025, Volume and Issue: 13(6), P. 1271 - 1271

Published: May 22, 2025

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 crucial role in maintaining homeostasis under conditions of cellular stress inflammation. Its pharmacological are primarily mediated through peroxisome proliferator-activated receptor-alpha (PPAR-α) activation, alongside indirect modulation cannabinoid receptors CB1 CB2, as well interactions with novel targets such GPR55 TRPV1. These molecular mechanisms underpin broad therapeutic potential, particularly management neuroinflammatory neurodegenerative disorders, syndromes, dysregulation. A major advancement research has been development ultramicronized palmitoylethanolamide (umPEA), which significantly enhances bioavailability efficacy by facilitating better tissue absorption interaction key pathways. Preclinical clinical studies have demonstrated that umPEA effective reducing neuroinflammation, stabilizing mast cells, enhancing endocannabinoid system activity, making it promising candidate integrative approaches neuropsychiatric inflammatory diseases. Given well-established safety profile, represents attractive alternative or adjunct conventional anti-inflammatory analgesic therapies. This communication provides comprehensive overview action applications both umPEA, emphasizing their emerging practice personalized medicine.

Language: Английский

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Endocannabinoids and atherosclerosis: the future of therapeutic strategies—a review

Cardiology Plus, Journal Year: 2024, Volume and Issue: 9(4), P. 283 - 290

Published: Oct. 1, 2024

The endocannabinoid system (ECS) is a widespread cell signaling in the human body, composed of molecules-anandamide, 2-arachidonoyl glycerol, their primary receptors, and associated enzymes responsible for synthesis degradation. Together, these components ECS work harmoniously to maintain homeostasis. Cardiovascular disease (CVD) leading cause morbidity mortality worldwide, with atherosclerosis as principal risk factor. Atherosclerosis progressive characterized by formation lipid-rich plaques within walls medium large vessel arteries. This process begins endothelial damage and, progresses through cascade events, including lipid accumulation, fibrosis, calcification, that leads narrowing inflammation. resulting atheromatous plaque, along complications such rupture, thrombosis, or embolism contributes serious cardiovascular outcomes. role endocannabinoids pathology, particularly cannabinoid (CB) 1 2 receptors has gained attention. Studies have shown CB1 are pro-atherogenic while CB2 exhibit anti-atherogenic properties. Activation ECS, especially under ischemic conditions, promotes expression free radical production, which damages cells accelerates development atherosclerosis. Inhibition specific promise reducing complications, evidenced outcomes from major clinical trials (the Strategy Reduce Development Involving Administration Rimonabant - Intravascular Ultrasound Study [STRADIVARIUS]). These findings suggest targeting may offer novel therapeutic approach managing

Language: Английский

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Cannabinoids for treating psychiatric disorders in youth: a systematic review of randomized controlled trials

Child and Adolescent Psychiatry and Mental Health, Journal Year: 2024, Volume and Issue: 18(1)

Published: Dec. 18, 2024

Abstract Background Cannabinoids have been of increasing interest mainly due to their putative efficacy in a wide array psychiatric, psychosomatic, and neurological conditions. Aims This systematic review aims synthesize results from randomized placebo-controlled trials regarding the dosage cannabinoids as therapeutics psychiatric disorders children, adolescents, young adults. Methods All publications up June 30th, 2024, were included PubMed Embase. Eligibility criteria accordance with PRISMA-guidelines was applied. RCTs providing pre- post-treatment parameters on cannabinoid therapies for mental comparison controls an age range 0 25 years included. Effect sizes calculated Hedges’ g primary outcomes, multilevel random-effects meta-analysis conducted account dependent outcomes same study populations. Results We identified 7603 records, which 8 independent clinical (reported 9 publications) met pre-established eligibility criteria, comprising 474 unique participants (245 treatment, 229 control). Analysis 13 (of 7 trials) revealed modest positive overall effect symptom improvement or normalization brain physiology (Hedges’ = 0.308, 95% CI: 0.167, 0.448). Autism spectrum disorder studies showed most consistent evidence (g 0.264, 0.107, 0.421), while other conditions wider confidence intervals. Age-stratified analysis that adult populations (mean 23.3 years, n 5 outcomes) demonstrated higher 0.463, SD 0.402) compared pediatric 11.8 outcomes; 0.318, 0.212). Whole plant preparations 0.328, 0.083, 0.573) pharmaceutical 0.292, 0.069, 0.515) comparable effects. CBD dosages ranged 17.5 mg 600 per day, no significant correlation between size (ρ -0.014, p 0.963). Mild moderate side effects reported, but serious adverse events. Risk bias assessment low ( 3) high 5). Conclusion While effects, particularly autism disorders, current remains insufficient broadly recommend treating youth Larger, controlled standardized are needed establish definitive recommendations.

Language: Английский

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