CB1 Cannabinoid Receptor Agonists Induce Acute Respiratory Depression in Awake Mice

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107682 - 107682

Published: March 1, 2025

Recreational use of synthetic cannabinoid agonists (i.e., "spice compounds") that target the type 1 receptor (CB1) can cause acute respiratory failure in humans. However, Δ9-tetrahydrocannabinol (Δ9-THC), major psychoactive phytocannabinoid cannabis, is not traditionally thought to interact with brain system, based largely upon sparse labeling CB1 receptors medulla and relative safety suggested by widespread human use. Here we used whole body plethysmography RNAscope situ hybridization mice reconcile this conflict between conventional wisdom data. We examined effects full agonist CP55,940 Δ9-THC male female mice. potently dose-dependently suppressed minute ventilation tidal volume, decreasing measures effort peak inspiratory expiratory flow). Both cannabinoids reduced frequency, time while markedly increasing pause. Respiratory suppressive were fully blocked antagonist AM251, minimally impacted peripherally-restricted AM6545, occurred at doses lower than those produce cardinal behavioral signs activation. Using hybridization, also demonstrated extensive coexpression Cnr1 (encoding receptor) Oprm1 µ-opioid mRNA cells medullary pre-Bötzinger complex, a critical nucleus control. Our results show for present region essential breathing demonstrate suppression via activation central receptors.

Language: Английский

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The Endocannabinoid System: The Most Important System You Never Learned in School

Published: Jan. 1, 2025

Language: Английский

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Respiratory System

Published: Jan. 1, 2025

Language: Английский

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Role of the Endocannabinoid System in Fibromyalgia

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 230 - 230

Published: March 27, 2025

Fibromyalgia is a chronic disease marked by extensive musculoskeletal pain, persistent fatigue, and cognitive impairments. Despite its high prevalence, the underlying pathological mechanisms of fibromyalgia are still not fully elucidated. Emerging research has identified endocannabinoid system as an essential factor in modulating pain other symptoms related to fibromyalgia. The plays key role many physiological processes such perception, mood regulation, inflammation. This review provides powerful analysis principal aspects examines evidence regarding involvement this condition, focusing on influence modulation. Moreover, dysregulation patients will be examined, with assessment how variations levels receptor activity may contribute clinical manifestations condition. A better knowledge could lead development novel strategies for managing

Language: Английский

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Acute cannabis intoxication among the paediatric population

Frontiers in Toxicology, Journal Year: 2025, Volume and Issue: 7

Published: April 14, 2025

This narrative review synthesizes the toxicological, clinical and medico-legal aspects of paediatric cannabis intoxication. By providing a comprehensive overview, it aims to inform future research, guide policymaking, enhance toxicological practice in addressing this growing public health concern. The pharmacokinetics cannabinoid ingestion children are significantly influenced by immaturity their gastrointestinal tract metabolic enzyme systems, resulting altered oral bioavailability. Clinical data indicate that Δ9-tetrahydrocannabinol (THC)-related effects paediatricpaediatric patients typically emerge within 2 hours ingestion, with more severe symptoms developing 4 hours. endocannabinoid system (ECS) undergoes significant developmental changes, marked differences receptor expression distribution across fetal, neonatal, adult brains. During neurodevelopment, CB1 receptors exhibit unique patterns, including transient localization brainstem regions critical for neurovegetative functions. These dynamics likely explain children’s heightened sensitivity THC’s neurological effects, often outcomes compared adults. reliable detection cannabinoids involves integrating screening methods confirmatory analytical techniques. Urine immunoassay testing is widely considered an helpful toolto assess previous exposure, becoming positive 3–4 h ingestion. However, method prone false positives. Plasma THC concentration, when measured close event, offers valuable insights into quantity ingested correlation between exposure impairment window. Hair analysis, while useful distinguishing acute chronic use, susceptible various biases. rising incidence intoxication underscores urgent need targeted interventions stricter regulatory frameworks. Preventive measures such as child-resistant packaging, education campaigns, use during pregnancy essential mitigate risks. Clinicians should consider differential diagnosis presenting unexplained neurological, immune, or symptoms.

Language: Английский

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A novel injectable nanotherapeutic platform increasing the bioavailability and antitumor efficacy of Arachidonoylcyclopropylamide on an ectopic non-small cell lung cancer xenograft model: A randomized controlled trial

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown, P. 125153 - 125153

Published: Dec. 1, 2024

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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Δ9-Tetrahydrocannabinol Effects on Respiration and Heart Rate Across Route of Administration in Female and Male Mice

Cardiovascular Toxicology, Journal Year: 2023, Volume and Issue: 23(11-12), P. 349 - 363

Published: Sept. 20, 2023

Language: Английский

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