Inflammatory Disorder of Immune SystempCB-IMIDsNCT06842316
Effects of Phytocannabinoids on Immune Response and Autophagy During Chronic Immune-mediated Inflammatory Diseases
An observational study of Inflammatory Disorder of Immune System and Spondylitis, Ankylosing, run by Centre Hospitalier Régional d'Orléans at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammatory Disorder of Immune System, Spondylitis, Ankylosing, Arthritis, Rheumatoid
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 10 Apr 2025to 9 Apr 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: In this exploratory study, the study population will include subjects suffering from IMID with rheumatological expression: rheumatoid arthritis (RA), Spondyloarthropathies with or without IBD, Psoriatic arthritis (Rpso), systemic lupus erythematosus (SLE), Sjögren's disease.
Who may be able to join
- Male or female ≥ 18 years old
- 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
- Patient who has expressed consent to participate in the study
- Patients affiliated to social security
- 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.
Who cannot join
- Patient who received intravenous corticosteroid therapy less than 4 weeks ago
- Patient receiving oral corticosteroid therapy with a daily dose >15 mg/day
- Consumption of CBD and/or recreational cannabis and/or positive saliva test for cannabis consumption and/or CBD
- Pregnant and lactating women
- Persons under guardianship or curatorship
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
CHU d'ORLEANS
Orléans, 45067
Carine Pr SALLIOT, PhD, 2 38 22 99 22 ext. +33, carine.salliot@chu-orleans.fr
Carine Pr SALLIOT, PhD
About this study
Official title: In Vitro Effects of Phytocannabinoids on Immune Response and Autophagy During Chronic Immune-mediated Inflammatory Diseases
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).
Read the detailed description
Background:
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:
- The inflammatory profile (main objective)
- The expression profile of cannabinoid receptors
- 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
- Inflammatory Disorder of Immune System, Spondylitis, Ankylosing, Arthritis, Rheumatoid, Arthritis, Psoriatic, Inflammatory Bowel Diseases, Sjogren's Syndrome
- Being tested
- 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)
- Keywords
- IMIDs, phytocanabinoid, inflammatory effect, blood cells
- Medical subject headings
- Spondylitis, Ankylosing, Arthritis, Rheumatoid, Arthritis, Psoriatic, Inflammatory Bowel Diseases, Sjogren's Syndrome, Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Rheumatoid polyarthritis | 10 patients without, 10 patients under basic treatment (csDMARDs*) and 10 patients under biotherapy or targeted therapy Receives: Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease) | |
| Spondyloarthropathy | 20 patients with or without IBD, including 10 under biotherapy or targeted therapy Receives: Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease) | |
| Psoriatic arthritis | 10 patients without, 10 patients with basic treatment (csDMARD) and 10 patients under biotherapy or targeted therapy Receives: Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease) | |
| Systemic lupus erythematosus | 10 patients with connective tissue disease (Systemic lupus erythematosus) Receives: Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease) | |
| Sjögren's syndrome | 10 patients with connective tissue disease (Sjögren's syndrome) Receives: Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is to evaluate the biological effect of exposure of blood cells from patients suffering from IMID to different varieties of pCB extracts on the inflammatory profile.
The initial inflammatory profiles of patients will be established by evaluations at the transcriptomic and protein level.
Measured: One sample at inclusion for all patients
The primary outcome is to evaluate the immunological effect of exposure of blood cells from patients suffering from IMID to different varieties of pCB extracts on the inflammatory profile.
In plasma, the concentrations of cytokines and chemokines associated with inflammation, pro (mainly TNF-α IFN-α, but for instance also IL6, IL8, and IL1-β) and anti-inflammatory (for example IL-10) will be quantified in Multiplexed (34-plex type) or conventional ELISA. The level of expression of the corresponding transcripts, produced by the sorted subpopulations (cellular targets: polymorphonuclear, CD14+ monocyte, CD19+ B lymphocytes, CD4+ T4 lymphocytes and CD8+ T8 lymphocytes) will subsequently be reported by BRB-Seq [13] and/or by droplet RT-PCR (RT-ddPCR) assays. This quantification technique is reproducible, requires little starting biological material and is very efficient in detecting small quantities.
Measured: One sample at inclusion for all patients
Secondary outcomes (3)
Inflammatory and autophagic/apoptotic transcripts, as well as transcripts of the main phytocannabinoid receptors in subpopulations of sorted blood cells.
Quantify ex vivo (by BRB-Seq and/or droplet quantitative RT-PCR (RT-ddPCR)). nflammatory and autophagic/apoptotic transcripts, as well as transcripts of the main phytocannabinoid receptors in subpopulations of sorted blood cells (polymorphonuclear cells, CD14+ monocytes, CD19+ B lymphocytes, CD4+ T and CD8+ T cells and if possible, quantify the evolution, after induction of an inflammatory context, of transcripts.
Measured: One sample at inclusion for all patients
The main phytocannabinoid receptors in blood cells
Quantify ex vivo (by BRB-Seq and/or droplet quantitative RT-PCR (RT-ddPCR)). the expression profile of phyto and endocannabinoid receptors in the subpopulations will be established. Note that the development of this quantification of the transcripts of certain cytokines and several pCB receptors has already been carried out during previous work in the CBM laboratory (on French blood institution blood donors). Finally, an evaluation of mRNAs associated with apoptosis and autophagy could also be documented. Indeed, autophagy, a crucial biological function for the cell, linked to inflammation [14, 15], will also be evaluated, because the combined effects of pCB, pro-apoptotic, pro-autophagic and anti-inflammatory, have already been reported.
Measured: One sample at inclusion for all patients
The main autophagy genes and apoptosis genes such as caspases
Quantify ex vivo (by BRB-Seq and/or droplet quantitative RT-PCR (RT-ddPCR)). Inflammatory and autophagic/apoptotic transcripts, as well as transcripts of the main phytocannabinoid receptors in subpopulations of sorted blood cells (polymorphonuclear cells, CD14+ monocytes, CD19+ B lymphocytes, CD4+ T and CD8+ T cells, and quantify the evolution, after induction of an inflammatory context, of transcripts.
Measured: One sample at inclusion for all patients
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2025
- Study start10 Apr 2025
- Primary completion9 Apr 2027 (estimated)
- Study completion9 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Disorder of Immune SystemStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Régional d'Orléans
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carine Pr SALLIOT, Principal investigator, CHU Orléans
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06842316
- Sponsor's protocol ID
- CHUO-2024-14
- Acronym
- pCB-IMIDs
- Status last verified
- Dec 2025
- First submitted
- 13 Feb 2025
- Last updated
- 30 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25635955Phillips 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.
PubMed 26836199MECHOULAM 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.
PubMed 14324315Costiniuk 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.
PubMed 30659041Hanus 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.
PubMed 27722705Russo 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.
PubMed 21749363Costa 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.
PubMed 26732541Koay 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.
PubMed 24833710Lattanzi 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.
PubMed 30390221Reddy 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.
PubMed 36206806Becker 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.
PubMed 38388989Alpern 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.
PubMed 30999927Qian 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.
PubMed 28748360Zhong 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.
PubMed 27419869Liu 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.
PubMed 35115945
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vitro Effects of Phytocannabinoids on Immune Response and Autophagy During Chronic Immune-mediated Inflammatory Diseases
- ClinicalTrials.gov ID
- NCT06842316
- Acronym / sponsor ID
- pCB-IMIDs / CHUO-2024-14
- Conditions
- Inflammatory Disorder of Immune System, Spondylitis, Ankylosing, Arthritis, Rheumatoid, Arthritis, Psoriatic, Inflammatory Bowel Diseases, Sjogren's Syndrome
- Keywords
- IMIDs, phytocanabinoid, inflammatory effect, blood cells
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Centre Hospitalier Régional d'OrléansUniversity, hospital or other
- Study start
- 10 Apr 2025 (actual)
- Primary completion
- 9 Apr 2027 (estimated)
- Study completion
- 9 Apr 2027 (estimated)
- First posted
- 24 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Background:
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:
- The inflammatory profile (main objective)
- The expression profile of cannabinoid receptors
- 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.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Rheumatoid polyarthritis | – | Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)10 patients without, 10 patients under basic treatment (csDMARDs*) and 10 patients under biotherapy or targeted therapy |
| Spondyloarthropathy | – | Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)20 patients with or without IBD, including 10 under biotherapy or targeted therapy |
| Psoriatic arthritis | – | Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)10 patients without, 10 patients with basic treatment (csDMARD) and 10 patients under biotherapy or targeted therapy |
| Systemic lupus erythematosus | – | Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)10 patients with connective tissue disease (Systemic lupus erythematosus) |
| Sjögren's syndrome | – | Other: 1 blood sample, 40 mL (collection during a blood test, part of the standard of care for this disease)10 patients with connective tissue disease (Sjögren's syndrome) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- In this exploratory study, the study population will include subjects suffering from IMID with rheumatological expression: rheumatoid arthritis (RA), Spondyloarthropathies with or without IBD, Psoriatic arthritis (Rpso), systemic lupus erythematosus (SLE), Sjögren's disease.
Key inclusion criteria (5 listed)
- Male or female ≥ 18 years old
- 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
- Patient who has expressed consent to participate in the study
- Patients affiliated to social security
- 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.
Key exclusion criteria (5 listed)
- Patient who received intravenous corticosteroid therapy less than 4 weeks ago
- Patient receiving oral corticosteroid therapy with a daily dose >15 mg/day
- Consumption of CBD and/or recreational cannabis and/or positive saliva test for cannabis consumption and/or CBD
- Pregnant and lactating women
- Persons under guardianship or curatorship
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Psoriatic arthritis, Rheumatoid polyarthritis, Sjögren's syndrome, Spondyloarthropathy, Systemic lupus erythematosus |
Primary outcome
The primary outcome is to evaluate the biological effect of exposure of blood cells from patients suffering from IMID to different varieties of pCB extracts on the inflammatory profile.
Time frame: One sample at inclusion for all patients
The initial inflammatory profiles of patients will be established by evaluations at the transcriptomic and protein level.
The primary outcome is to evaluate the immunological effect of exposure of blood cells from patients suffering from IMID to different varieties of pCB extracts on the inflammatory profile.
Time frame: One sample at inclusion for all patients
In plasma, the concentrations of cytokines and chemokines associated with inflammation, pro (mainly TNF-α IFN-α, but for instance also IL6, IL8, and IL1-β) and anti-inflammatory (for example IL-10) will be quantified in Multiplexed (34-plex type) or conventional ELISA. The level of expression of the corresponding transcripts, produced by the sorted subpopulations (cellular targets: polymorphonuclear, CD14+ monocyte, CD19+ B lymphocytes, CD4+ T4 lymphocytes and CD8+ T8 lymphocytes) will subsequently be reported by BRB-Seq [13] and/or by droplet RT-PCR (RT-ddPCR) assays. This quantification technique is reproducible, requires little starting biological material and is very efficient in detecting small quantities.
3 secondary outcomes
Inflammatory and autophagic/apoptotic transcripts, as well as transcripts of the main phytocannabinoid receptors in subpopulations of sorted blood cells.
Time frame: One sample at inclusion for all patients
The main phytocannabinoid receptors in blood cells
Time frame: One sample at inclusion for all patients
The main autophagy genes and apoptosis genes such as caspases
Time frame: One sample at inclusion for all patients
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2025.
- Background: PubMed 25635955Boychuk 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.
- Background: PubMed 26836199Phillips 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.
- Background: PubMed 14324315MECHOULAM 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.
- Background: PubMed 30659041Costiniuk 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.
- Background: PubMed 27722705Hanus 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.
- Background: PubMed 21749363Russo 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.
- Background: PubMed 26732541Costa 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.
- Background: PubMed 24833710Koay 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.
- Background: PubMed 30390221Lattanzi 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.
- Background: PubMed 36206806Reddy 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.
- Background: PubMed 38388989Becker 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.
- Background: PubMed 30999927Alpern 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Carine Pr SALLIOT principal investigator
CHU Orléans
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Disorder of Immune System and Spondylitis, Ankylosing, run by Centre Hospitalier Régional d'Orléans at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carine Pr SALLIOT, PhD (02 38 22 99 22 ext. +33, carine.salliot@chu-orleans.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome is to evaluate the biological effect of exposure of blood cells from patients suffering from IMID to different varieties of pCB extracts on the inflammatory profile. (time frame: One sample at inclusion for all patients). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06842316, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2025.