Study on the Effects of Drugs That Modulate the Endocannabinoid System on Spontaneous and Induced Contractility of the Human Detrusor Muscle

Study on the Effects of Drugs That Modulate the Endocannabinoid System on Spontaneous and Induced Contractility of the Human Detrusor Muscle

The goal of this observational, in vitro study is to evaluate the effects of drugs that modulate the endocannabinoid system on spontaneous and neuronally induced contractility of the human detrusor. The study will include adult patients undergoing elective radical cystectomy for bladder cancer. The main questions it aims to answer are whether modulation of endocannabinoid receptors, enzymes involved in endocannabinoid synthesis and degradation, and endocannabinoid transport mechanisms alters basal detrusor contractility and modifies excitatory motor responses induced by neuronal activation.

Participants undergoing radical cystectomy will provide written informed consent for the collection of a small sample of macroscopically healthy bladder tissue from the surgical specimen. Detrusor muscle strips will be prepared and studied in vitro using organ bath techniques. Contractile activity will be recorded under baseline conditions and after electrical field stimulation, as well as following exposure to pharmacological modulators of the endocannabinoid system. Demographic, clinical, and pathological data will also be collected for descriptive analysis.

This is a prospective, monocentric, observational in vitro study designed to investigate the role of the endocannabinoid system in the regulation of human detrusor contractility. The study evaluates the effects of pharmacological modulation of endocannabinoid receptors, enzymes involved in endocannabinoid synthesis and degradation, and endocannabinoid transport mechanisms on both spontaneous and neuronally induced contractile activity of human detrusor muscle.

The endocannabinoid system has been implicated in the regulation of lower urinary tract function, including sensory signaling and smooth muscle contractility. Experimental evidence suggests that cannabinoid receptor activation may modulate neurotransmitter release and detrusor muscle activity. However, most available data derive from animal models, and findings in human tissues remain limited and sometimes conflicting. A better characterization of the role of endocannabinoid signaling in human detrusor contractility may provide insight into potential therapeutic targets for disorders such as detrusor overactivity and overactive bladder syndrome.

Bladder tissue samples will be obtained from surgical specimens and processed for in vitro functional studies. Detrusor muscle strips will be prepared and mounted in organ baths to record contractile responses under controlled experimental conditions. Baseline motor activity and responses to neuronal stimulation will be assessed. Preparations will then be exposed to pharmacological agents acting on different components of the endocannabinoid system, including receptor agonists and antagonists, allosteric modulators, inhibitors of endocannabinoid biosynthesis and degradation, and inhibitors of endocannabinoid transport. Changes in contractile activity will be evaluated to characterize the functional contribution of these pathways.

The experimental procedures will be conducted in sequential phases to characterize baseline contractile responses, assess receptor-mediated effects, and evaluate the impact of modulation of endocannabinoid metabolism and transport. Clinical and demographic data will be recorded for descriptive purposes. The study is exploratory in nature and aims to generate mechanistic data on the role of the endocannabinoid system in human detrusor physiology.

Inclusion Criteria:

• Age ≥ 18 years.
• Patients with bladder carcinoma at any stage of disease, undergoing upfront surgery or neoadjuvant therapy for more than 6 weeks, scheduled for surgery with curative/demolitive intent.
• Signed written informed consent to participate in the study.

Exclusion Criteria:

• Age < 18 years.
• Procedures performed on an urgent/emergency basis.
• Patients treated with corticosteroid therapy for immunorheumatic diseases.
• Patients treated with radio-chemotherapy and undergoing surgery less than 6 weeks prior.
• Refusal to sign written informed consent to participate in the study.