Effects of Phytocannabinoids on Immune Response and Autophagy During Chronic Immune-mediated Inflammatory Diseases

Summary

Cannabis, in addition to its psychotropic properties, could have anti-inflammatory and immunomodulatory effects. Phytocannabinoids (pCBs) are a group of molecules naturally secreted by the cannabis plant. The major pCBs are cannabidiol (CBD) and Δ9-tetrahydrocannabinol Δ9 (THC). Only THC has psychotropic effects, which CBD does not have. Alongside these two main components, there is a wide variety of other molecules, such as other pCBs and terpenes which could increase the effects on immune system through synergistic interactions between these different compounds ("entourage effect").In vivo, pCBs essentially interfere with the endocannabinoid system, acting on many ubiquitous receptors, present on a significant number of different cell types. Numerous published studies show that pCBs have immunomodulatory and anti-inflammatory properties by acting on several of these receptors, whether through modulation of the immune response of different cell types, effects on cytokine networks, reduction of innate and adaptive responses and/or impact on cell survival or death (autophagy, proliferation/ apoptosis). The Immune-Mediated Inflammatory Diseases (IMIDs) affect 5 to 7% of the general population in Western countries, involve different organs (joints, skin, digestive tract) but share the same inflammatory mechanisms resulting from a dysregulation of the immune response. Our research focuses on the identification of the most effective phytochemical profile of pCBs, allowing an optimal effect on chronic inflammatory pathologies of interest among immune-mediated chronic inflammatory diseases (IMIDs). The pCB-IMIDs project is therefore part of an innovative translational project, around new therapeutic applications of medical cannabis (CannAppIMIDs). In our study, we will include 100 patients with one of IMIDs among Rheumatoid Arthritis, spondylarthritis, psoriatic arthritis, Sjogren disease and systemic lupus, at different stage and with different treatments. After patient's consent we will collect for research purposes an additional 40 ml of blood during a routine care blood test. Mononuclear and polynucleated blood cells will be exposed in vitro to different full-spectrum pCB extracts (full spectrum extract) including a CBD dominant and low THC extract (\<0.2%), 1 dominant THC extract, 1 balanced THC/CBD extract and 1 dominant CBG extract. In this cross-sectional study, our objective will be to assess the biological effects of different pCB compositions on inflammatory profiles (concentrations of pro and anti-inflammatory cytokines and chemokines) and modulations of expression profiles (autophagy, apoptosis, and cannabinoid receptor expression profile).

Conditions

• Inflammatory Disorder of Immune System
• Spondylitis, Ankylosing
• Arthritis, Rheumatoid
• Arthritis, Psoriatic
• Inflammatory Bowel Diseases
• Sjogren's Syndrome
• Lupus Erythematosus, Systemic

Interventions

OTHER

1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)

Mononuclear and polynuclear peripheral blood cells from subjects suffering from IMID will be exposed in vitro to different inflammatory inducers with and without the concomitant addition of at least 4 different pCB extracts spectrum complete (full spectrum) including a dominant CBD extract and low in THC (\<0.2%), 1 dominant THC extract, 1 balanced THC/CBD extract and 1 dominant CBG extract. The same analyzes will be carried out in the presence of a recognized anti-inflammatory (for example hydrocortisone or dexamethasone) which will thus be used as a positive control.

Sponsors & Collaborators

• Centre Hospitalier Régional d'Orléans

  lead OTHER

Principal Investigators

• Carine Pr SALLIOT · CHU Orléans

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-04-10

Primary Completion

2027-04-09

Completion

2027-04-09

Countries

• France

Study Locations