Effects of Phytocannabinoids on Immune Response and Autophagy During Chronic Immune-mediated Inflammatory Diseases
NCT ID: NCT06842316
Last Updated: 2025-12-30
Study Results
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Basic Information
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RECRUITING
100 participants
OBSERVATIONAL
2025-04-10
2027-04-09
Brief Summary
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Detailed Description
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The analgesic and anxiolytic properties of cannabis are at the origin of the French experiment on medical cannabis set up in 2020 and led by the ANSM (National Agency for the Safety of Medicines and Health Products) for 5 well-identified pathologies (neuropathic pain, certain forms of pediatric epilepsy, symptoms linked to cancer or anti-cancer treatment, palliative situations and painful spasticity linked to multiple sclerosis). Phytocannabinoids (pCBs) are a group of molecules naturally secreted by the cannabis plant. The main pCBs are cannabidiol (CBD) and Δ9-tetrahydrocannabinol Δ9-THC \[1, 2\]. Only THC has psychotropic effects, which CBD does not have. Alongside these two main components, there is a wide variety of molecules \[cannabigerol (CBG), cannabinol (CBN), cannabichromene (CBC) and other terpenes\] which are said to have an "entourage effect" by increasing the effects by synergistic interactions between these different compounds \[3-7\]. CBD of natural origin can be purified without other terpenes corresponding to CBD alone ("CBD isolate") or is combined with terpenes and phytocannabinoids but without THC or any other pCB ("broad spectrum"), or in unpurified form, CBD with terpenes and THC ("full spectrum").
In vivo, pCBs essentially interfere with the endocannabinoid system, acting on numerous receptors present on a large number of different cell types \[8\]. This means that pCBs can be used to treat a wide range of organs. Numerous published works show that pCBs have immunomodulatory and anti-inflammatory properties by acting on several of these receptors, whether via modulation of the immune response of different cell types, effects on cytokine networks, reduction of innate and adaptive responses \[9, 10\] and/or impact on cell survival or death (autophagy, proliferation/apoptosis) \[8, 9\]. Thus, in addition to its neurological effects \[10, 11\], cannabis possesses anti-inflammatory, pro-autophagic and anti-proliferative properties, which are still imperfectly characterized.
Understanding the mechanisms of action of pCBs, individually or in combination with other molecules present in cannabis, on different therapeutic targets therefore presents an immense challenge in the management of Immune-Mediated Inflammatory Diseases (IMIDs). These IMIDs affect 5 to 7% of the general population in Western countries, and involve different organs (joints, skin, gut) but share the same inflammatory mechanisms, resulting from a deregulation of the immune response.
The pCB-IMIDs project is part of an innovative translational project focusing on new therapeutic applications for medical cannabis (CannAppIMIDs).
Objectives:
The objective of this exploratory project is to evaluate the biological and immunological effects of exposure of blood cells from patients suffering from IMID to different varieties of pCB extracts on:
1. The inflammatory profile (main objective)
2. The expression profile of cannabinoid receptors
3. The autophagic and apoptotic profile
Methods: Single-center cross-sectional study without prospective follow-up of participants, classified non-interventional study. The study consists, after obtaining consent and verifying the eligibility criteria (with saliva test specific to the study), in taking an additional 40 ml of blood during a planned blood test for research purposes and to collect medical data on patients and their inflammatory pathology.
Mononuclear and polynuclear blood cells from subjects suffering from IMID will be exposed in vitro to different inflammatory inducers used individually and/ or all together (LPS- bacterial Lipopolysaccahride, TLR-4 ligand and/or poly-I:C , TLR-3 ligand and/or PAM3CSK4, TLR1/TLR2 ligand, and/or PHA-P - phytohemagglutin P, polysaccharide and glycoprotein ligand) with and without the concomitant addition of different complete spectrum of pCB extracts (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 serve as a positive control \[12\].
All analyses will be carried out at CBM - UPR4301 CNRS. Results will allow us to formulate hypotheses, guide and argue for future clinical research studies evaluating the benefit(s) and tolerance of extracts rich in pCB in taking in therapeutic management of IMIDs.
Conditions
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Keywords
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Study Design
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OTHER
CROSS_SECTIONAL
Study Groups
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Rheumatoid polyarthritis
10 patients without, 10 patients under basic treatment (csDMARDs\*) and 10 patients under biotherapy or targeted therapy
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.
Spondyloarthropathy
20 patients with or without IBD, including 10 under biotherapy or targeted therapy
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.
Psoriatic arthritis
10 patients without, 10 patients with basic treatment (csDMARD) and 10 patients under biotherapy or targeted therapy
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.
Systemic lupus erythematosus
10 patients with connective tissue disease (Systemic lupus erythematosus)
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.
Sjögren's syndrome
10 patients with connective tissue disease (Sjögren's syndrome)
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.
Interventions
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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.
Eligibility Criteria
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Inclusion Criteria
2. Diagnosis confirmed by a rheumatologist of RA or spondyloarthropathy (with or without IBD) or psoriatic arthritis (with or without active psoriasis) or systemic lupus erythematosus or Sjögren's disease
3. Patient who has expressed consent to participate in the study
4. Patients affiliated to social security
5. Treatments authorized as part of routine care: non-steroidal anti-inflammatory drugs (NSAIDs), level 1 to 3 analgesics, local corticosteroids, oral corticosteroid therapy (daily dose ≤15 mg/d), 5-aminosalicylic acid, salazopyrine, methotrexate, leflunomide, hydroxychloroquine, biotherapies and targeted therapies.
Exclusion Criteria
2. Patient receiving oral corticosteroid therapy with a daily dose \>15 mg/day
3. Consumption of CBD and/or recreational cannabis and/or positive saliva test for cannabis consumption and/or CBD
4. Pregnant and lactating women
5. Persons under guardianship or curatorship
18 Years
ALL
No
Sponsors
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Centre Hospitalier Régional d'Orléans
OTHER
Responsible Party
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Principal Investigators
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Carine Pr SALLIOT
Role: PRINCIPAL_INVESTIGATOR
CHU Orléans
Locations
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CHU d'ORLEANS
Orléans, , France
Countries
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Central Contacts
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Facility Contacts
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Carine Pr SALLIOT, PhD
Role: primary
References
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Boychuk DG, Goddard G, Mauro G, Orellana MF. The effectiveness of cannabinoids in the management of chronic nonmalignant neuropathic pain: a systematic review. J Oral Facial Pain Headache. 2015 Winter;29(1):7-14. doi: 10.11607/ofph.1274.
Phillips RS, Friend AJ, Gibson F, Houghton E, Gopaul S, Craig JV, Pizer B. Antiemetic medication for prevention and treatment of chemotherapy-induced nausea and vomiting in childhood. Cochrane Database Syst Rev. 2016 Feb 2;2(2):CD007786. doi: 10.1002/14651858.CD007786.pub3.
MECHOULAM R, GAONI Y. A TOTAL SYNTHESIS OF DL-DELTA-1-TETRAHYDROCANNABINOL, THE ACTIVE CONSTITUENT OF HASHISH. J Am Chem Soc. 1965 Jul 20;87:3273-5. doi: 10.1021/ja01092a065. No abstract available.
Costiniuk CT, Saneei Z, Routy JP, Margolese S, Mandarino E, Singer J, Lebouche B, Cox J, Szabo J, Brouillette MJ, Klein MB, Chomont N, Jenabian MA. Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028-study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation. BMJ Open. 2019 Jan 17;9(1):e024793. doi: 10.1136/bmjopen-2018-024793.
Hanus LO, Meyer SM, Munoz E, Taglialatela-Scafati O, Appendino G. Phytocannabinoids: a unified critical inventory. Nat Prod Rep. 2016 Nov 23;33(12):1357-1392. doi: 10.1039/c6np00074f.
Russo EB. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011 Aug;163(7):1344-64. doi: 10.1111/j.1476-5381.2011.01238.x.
Costa L, Amaral C, Teixeira N, Correia-da-Silva G, Fonseca BM. Cannabinoid-induced autophagy: Protective or death role? Prostaglandins Other Lipid Mediat. 2016 Jan;122:54-63. doi: 10.1016/j.prostaglandins.2015.12.006. Epub 2015 Dec 28.
Koay LC, Rigby RJ, Wright KL. Cannabinoid-induced autophagy regulates suppressor of cytokine signaling-3 in intestinal epithelium. Am J Physiol Gastrointest Liver Physiol. 2014 Jul 15;307(2):G140-8. doi: 10.1152/ajpgi.00317.2013. Epub 2014 May 15.
Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, Silvestrini M. Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis. Drugs. 2018 Nov;78(17):1791-1804. doi: 10.1007/s40265-018-0992-5.
Reddy DS. Therapeutic and clinical foundations of cannabidiol therapy for difficult-to-treat seizures in children and adults with refractory epilepsies. Exp Neurol. 2023 Jan;359:114237. doi: 10.1016/j.expneurol.2022.114237. Epub 2022 Oct 4.
Becker L, Holtmann D. Anti-inflammatory effects of alpha-humulene on the release of pro-inflammatory cytokines in lipopolysaccharide-induced THP-1 cells. Cell Biochem Biophys. 2024 Jun;82(2):839-847. doi: 10.1007/s12013-024-01235-7. Epub 2024 Feb 22.
Alpern D, Gardeux V, Russeil J, Mangeat B, Meireles-Filho ACA, Breysse R, Hacker D, Deplancke B. BRB-seq: ultra-affordable high-throughput transcriptomics enabled by bulk RNA barcoding and sequencing. Genome Biol. 2019 Apr 19;20(1):71. doi: 10.1186/s13059-019-1671-x.
Qian M, Fang X, Wang X. Autophagy and inflammation. Clin Transl Med. 2017 Dec;6(1):24. doi: 10.1186/s40169-017-0154-5. Epub 2017 Jul 26.
Zhong Z, Sanchez-Lopez E, Karin M. Autophagy, Inflammation, and Immunity: A Troika Governing Cancer and Its Treatment. Cell. 2016 Jul 14;166(2):288-298. doi: 10.1016/j.cell.2016.05.051.
Liu QR, Aseer KR, Yao Q, Zhong X, Ghosh P, O'Connell JF, Egan JM. Anti-Inflammatory and Pro-Autophagy Effects of the Cannabinoid Receptor CB2R: Possibility of Modulation in Type 1 Diabetes. Front Pharmacol. 2022 Jan 18;12:809965. doi: 10.3389/fphar.2021.809965. eCollection 2021.
Other Identifiers
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CHUO-2024-14
Identifier Type: -
Identifier Source: org_study_id