Chronic PainPhase 2ORIONNCT07783295
Full-Spectrum Cannabis Extract for Chronic Pain and Bone Health Biomarkers in Women
A Phase 2 study testing Full-Spectrum Cannabis Extract 5:1 (CBD:THC) in people with Chronic Pain and Fibromyalgia, run by Associação Pan-Americana Multidisciplinar de Endocanabinologia at 1 site in Brazil.
Trial summary
Chronic pain disproportionately affects women and may coexist with impaired bone health, particularly during midlife and after menopause. The endocannabinoid system is involved in pain modulation and bone homeostasis; however, clinical studies that integrate pain outcomes, bone-related biomarkers, genetic variants… Read more about this study
- Who is it for?
- Ages 45 to 80 years, women only
- Conditions the study is for
- Chronic Pain, Fibromyalgia, Osteoporosis
- What is being tested?
- Full-Spectrum Cannabis Extract 5:1 (CBD:THC)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Sep 2026to 1 Dec 2027
- Phase
- Phase 2
- 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 45 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female sex, age 45 to 80 years
- Moderate to severe chronic pain, defined as a pain score of at least 4 on a 0 to 10 Visual Analog Scale, persisting for more than 3 months
- Documented inadequate response to at least 2 classes of analgesic treatments or non-pharmacological treatments
- Willingness to abstain from smoked cannabis and non-study cannabinoid products during the study
- Ability to understand the informed consent form and study questionnaires
- Willingness and ability to attend scheduled visits and biological sample collections during the study follow-up period
Who cannot join
- Cognitive impairment that precludes understanding of the informed consent form or study questionnaires
- Uncontrolled psychiatric condition, including uncontrolled psychotic disorder or bipolar disorder
- Pregnancy, breastfeeding, or intention to become pregnant during the study
- Current use of medicinal cannabis, smoked cannabis, or other cannabinoid products
- Known hypersensitivity to cannabinoids or formulation excipients
- Clinically significant hepatic impairment, defined as aspartate aminotransferase or alanine aminotransferase greater than 3 times the upper limit of normal, or severe heart failure classified as New York Heart Association class III or IV
- History of substance use disorder that, in the investigator's judgment, may interfere with study participation
- Use of medications that may interfere with bone metabolism, including bisphosphonates, systemic corticosteroids, or sex hormones, within 6 months before enrollment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site
Projeto Shalom
São Paulo, São Paulo, 09130-040
Alethéia B P Barbosa, PhD, +55 11 97247-1484, abpablos@gmail.com
José Wilson N V Andrade, MD, + 55 11 971905328, dr.jwilsonandrade@gmail.com
About this study
Official title: Evaluation of Bone Turnover Biomarkers, CB2 and TRPV1 Polymorphisms as Potential Preventive Data in Osteoporosis and Perception of Improvement in Quality of Life in Women With Chronic Pain Treated With Medicinal Cannabis
Chronic pain disproportionately affects women and may coexist with impaired bone health, particularly during midlife and after menopause. The endocannabinoid system is involved in pain modulation and bone homeostasis; however, clinical studies that integrate pain outcomes, bone-related biomarkers, genetic variants, and salivary endocannabinoids remain limited.This randomized, triple-masked, placebo-controlled crossover trial will evaluate the effects of a full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 on chronic pain in women aged 45 to 80 years with chronic pain refractory to conventional treatment. Eighty participants will be randomly assigned to one of two treatment sequences: full-spectrum cannabis extract followed by matching placebo, or matching placebo followed by full-spectrum cannabis extract. The treatment periods, washout interval, and visit schedule will follow the final approved protocol.The primary outcome is change in chronic pain intensity measured using the Visual Analog Scale. Secondary outcomes include quality of life, sleep quality, functional impact, bone health biomarkers, bone mineral density measured by dualenergy X-ray absorptiometry, salivary endocannabinoids, the association of CB and TRPV genetic variants with treatment response, and adverse events. The study aims to generate evidence on the clinical effects and biological correlates of medicinal cannabis therapy in women with chronic pain.
Read the detailed description
This is a randomized, triple-masked, placebo-controlled crossover clinical trial conducted in women aged 45 to 80 years with moderate to severe chronic pain that has persisted for at least 3 months and has not responded adequately to conventional pharmacological or non-pharmacological treatments. Participants will be randomlyallocated in permuted blocks to one of two treatments sequences. Sequence A will receive a full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during the first treatment period, followed by a protocol-defined washout interval and matching placebo during the second treatment period. Sequence B will receive matching placebo during the first treatment period, followed by the washout interval and the full-spectrum medicinal cannabis extract during the second treatment period. The study product will be administered orally as softgel capsules. The target daily dose is 25 milligrams of cannabidiol and 5 milligrams of tetrahydrocannabinol. Dose titration during the first 2 weeks of each active treatment period will follow the final approved protocol.Participants, care providers, investigators, and outcome assessors will remain masked to treatment assignment as operationally applicable. Randomization will use a computer-generated sequence with permuted blocks of 4 and allocation concealment through opaque, sealed envelopes. The product and matching placebo will be supplied in indistinguishable presentations.Clinical evaluations will include pain intensity, quality of life, functional impact, sleep quality, concomitant medications, adherence, and adverse events. Laboratory assessments will include safety tests, selected bone metabolism biomarkers, inflammatory markers, and oxidative stress biomarkers. Bone mineral density and body composition will be assessed using dualenergy X-ray absorptiometry at protocol-defined baseline and final visits. Genetic analysis will evaluate CB and TRPV variants. Salivary anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide will be quantified using liquid chromatography coupled with tandem mass spectrometry according to the final sample collection schedule.The primary efficacy analysis will compare pain outcomes across cannabis and placebo treatment periods while accounting for the crossover design. Secondary analyses will evaluate changes in patient-reported outcomes and biomarkers, treatment safety, and associations between genetic variants or salivary endocannabinoid profiles and treatment response.
- Conditions
- Chronic Pain, Fibromyalgia, Osteoporosis, Orofacial Pain
- Being tested
- Full-Spectrum Cannabis Extract 5:1 (CBD:THC)
- Keywords
- medical cannabis, cannabidiol, tetrahydrocannabinol, bone turnover, CB1 receptor, CB2 receptor, TRPV1 receptor, Women, crossover trial, bone mineral density, chronic pain
- Medical subject headings
- Chronic Pain, Fibromyalgia, Osteoporosis, Facial Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Full-Spectrum Cannabis Extract 5:1 (CBD:THC)Drug
Oral softgel capsule containing full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1. The target daily dose is 25 milligrams of cannabidiol and 5 milligrams of tetrahydrocannabinol. Participants will receive the study product once daily in the evening, with gradual dose titration during the first 2 weeks of each active treatment period, according to the final approved protocol. The product will be administered for the duration of each protocol-defined active treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Cannabis Extract Then Placebo | Experimental | Participants receive oral full-spectrum cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during Treatment Period 1, followed by the protocol-defined washout interval and matching placebo during Treatment Period 2. Receives: Drug: Full-Spectrum Cannabis Extract 5:1 (CBD:THC) |
| Placebo Then Cannabis Extract | Placebo comparator | Participants receive matching placebo during Treatment Period 1, followed by the protocol-defined washout interval and oral full-spectrum cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during Treatment Period 2. Receives: Drug: Full-Spectrum Cannabis Extract 5:1 (CBD:THC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Period Baseline in Chronic Pain Intensity on the Visual Analog Scale
Chronic pain intensity will be measured using a 0 to 10 Visual Analog Scale, where 0 indicates no pain and 10 indicates the worst imaginable pain. The baseline score will be the mean pain intensity reported over the preceding 7 days. A clinical response is defined as a reduction of at least 30 percent from the baseline score of the corresponding treatment period.
Measured: At the baseline and end of each treatment period, approximately 6 months per period.
Secondary outcomes (10)
Change From Period Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index.
Sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI), a self-reported instrument with a global score from 0 to 21. Higher scores indicate worse sleep quality.
Measured: At baseline and at 3 and 6 Months each treatment period.
Change From Period Baseline in Health-Related Quality of Life on the 36-Item Short Form Survey.
Health-related quality of life will be assessed using the Medical Outcomes Study 36-Item Short Form Survey (SF-36). Scores are calculated for 8 domains from 0 to 100; higher scores indicate better health-related quality of life.
Measured: At baseline and at Months 3 and 6 of each treatment period.
Change From Period Baseline in Pain-Related Quality of Life on the WHOQOL-Pain Instrument.
Pain-related quality of life will be assessed using the Portuguese version of the WHOQOL-Pain instrument. Scoring and interpretation will follow the validated instrument manual.
Measured: At baseline and at Months 3 and 6 of each treatment period.
Change From Period Baseline in Fibromyalgia Impact Questionnaire Score Among Participants With Fibromyalgia.
Functional impact among participants with a clinical diagnosis of fibromyalgia will be assessed using the Fibromyalgia Impact Questionnaire (FIQ). The scale will be scored according to the validated Portuguese version; higher scores indicate greater disease impact.
Measured: At baseline and at Months 3 and 6 of each treatment period.
Change From Baseline in Bone Mineral Density Measured by Dual-Energy X-Ray Absorptiometry.
Bone mineral density and body composition will be assessed using dual-energy X-ray absorptiometry (DXA). Bone mineral density will be reported in grams per square centimeter and interpreted using T-scores according to applicable clinical criteria.
Measured: At baseline and at the final study visit, approximately 12 months after enrollment.
Change From Period Baseline in Serum Bone Turnover Biomarkers.
Serum bone health biomarkers will include the final protocol-specified panel of alkaline phosphatase, total and ionized calcium, 25-hydroxyvitamin D, and parathyroid hormone. If procollagen type 1 N-terminal propeptide and C-terminal telopeptide are retained in the final protocol, they should be listed here explicitly.
Measured: At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
Association of CB2 and TRPV1 Genetic Variants With Pain Treatment Response.
Genotyping of cannabinoid receptor 2 (CB2/CNR2) and transient receptor potential vanilloid 1 (TRPV1) variants will be performed using real-time polymerase chain reaction. Associations between genotype or haplotype and the prespecified Visual Analog Scale pain response will be evaluated.
Measured: Genotyping at baseline; association with pain response through the end of each treatment period, approximately 12 months.
Change From Baseline in Salivary Endocannabinoid Concentrations.
Salivary concentrations of anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide will be quantified by liquid chromatography-tandem mass spectrometry and reported in nanograms per milliliter.
Measured: Use the final collection schedule; do not submit this entry until the protocol is harmonized as baseline-only or serial sampling.
Number of Participants With Treatment-Emergent Adverse Events.
Adverse events will be collected through clinical visits and weekly remote pharmacotherapeutic monitoring. Events will be classified by severity, seriousness, relatedness to study treatment, and treatment period.
Measured: From first study product administration through the end of each treatment period, approximately 6 months per period.
Change From Period Baseline in Hepatic and Renal Safety Laboratory Values.
Safety laboratory assessments will include protocol-specified hepatic and renal tests, including aspartate aminotransferase, alanine aminotransferase, urea, and creatinine. Results will be reported in standard laboratory units.
Measured: At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (74)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants will be randomly assigned in a 1:1 ratio to one of two crossover sequences. Sequence A will receive full-spectrum cannabis extract during Period 1 and matching placebo during Period 2. Sequence B will receive matching placebo during Period 1 and full-spectrum cannabis extract during Period 2. The treatment periods will be separatedby a protocol-defined washout interval. Randomization will use computer-generated permuted blocks of 4 with allocation concealment through opaque, sealed envelopes.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Associação Pan-Americana Multidisciplinar de Endocanabinologia
- Sponsor type
- University, hospital or other
- Collaborators
- Mackenzie Presbiterian University, São Paulo, Brazil, Associação Brasileira de Cannabis Medicinal
- Responsible party
- Sponsor
- Investigators
- Alethéia B P Barbosa, PhD, Principal investigator, Universidade Presbiteriana Mackenzie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07783295
- Sponsor's protocol ID
- UPM-BONE-RELIEF-01
- Acronym
- ORION
- Status last verified
- Aug 2026
- First submitted
- 20 Aug 2026
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Andreis K, Billingsley J, Naimi Shirazi K, Wager-Miller J, Johnson C, Bradshaw H, Straiker A. Cannabinoid CB1 receptors regulate salivation. Sci Rep. 2022 Aug 19;12(1):14182. doi: 10.1038/s41598-022-17987-2.
PubMed 35986066de Melo Reis RA, Isaac AR, Freitas HR, de Almeida MM, Schuck PF, Ferreira GC, Andrade-da-Costa BLDS, Trevenzoli IH. Quality of Life and a Surveillant Endocannabinoid System. Front Neurosci. 2021 Oct 28;15:747229. doi: 10.3389/fnins.2021.747229. eCollection 2021.
PubMed 34776851Cupini LM, Bari M, Battista N, Argiro G, Finazzi-Agro A, Calabresi P, Maccarrone M. Biochemical changes in endocannabinoid system are expressed in platelets of female but not male migraineurs. Cephalalgia. 2006 Mar;26(3):277-81. doi: 10.1111/j.1468-2982.2005.01031.x.
PubMed 16472333Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016 Jul 1;1(1):154-165. doi: 10.1089/can.2016.0009. eCollection 2016.
PubMed 28861491Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2008 Apr;29(2):192-200.
PubMed 18404144Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):31-9.
PubMed 15159679Zimmer A. A collaboration investigating endocannabinoid signalling in brain and bone. J Basic Clin Physiol Pharmacol. 2016 May 1;27(3):229-35. doi: 10.1515/jbcpp-2015-0125.
PubMed 26887036Macedo CG, Fanton LE, Fischer L, Tambeli CH. Coactivation of mu- and kappa-Opioid Receptors May Mediate the Protective Effect of Testosterone on the Development of Temporomandibular Joint Nociception in Male Rats. J Oral Facial Pain Headache. 2016 Winter;30(1):61-7. doi: 10.11607/ofph.1298.
PubMed 26817034Leucuta DC, Anton D, Almasan O. Estrogen Hormones' Implications on the Physiopathology of Temporomandibular Dysfunction. J Clin Med. 2024 Jul 27;13(15):4406. doi: 10.3390/jcm13154406.
PubMed 39124673Fischer L, Torres-Chavez KE, Clemente-Napimoga JT, Jorge D, Arsati F, de Arruda Veiga MC, Tambeli CH. The influence of sex and ovarian hormones on temporomandibular joint nociception in rats. J Pain. 2008 Jul;9(7):630-8. doi: 10.1016/j.jpain.2008.02.006.
PubMed 18420460Ferraris C, Scarlett CJ, Veysey M, Lucock M, Bucher T, Beckett EL. Salt-Taste Polymorphism TRPV1-rs8065080 Is Associated with Increased Likelihood of Depression in an Elderly Cohort. Lifestyle Genom. 2023;16(1):224-236. doi: 10.1159/000534521. Epub 2023 Oct 26.
PubMed 37883944Giacon M, Cargnin S, Allena M, Greco R, Zanaboni AM, Facchetti S, De Icco R, Sances G, Ghiotto N, Guaschino E, Martinelli D, Tassorelli C, Terrazzino S. Lack of association between TRPV1 gene polymorphisms and risk of migraine chronification: a case-control study and meta-analysis. Neurol Sci. 2025 Jan;46(1):303-312. doi: 10.1007/s10072-024-07724-0. Epub 2024 Aug 6.
PubMed 39105976Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study. J Am Geriatr Soc. 2002 Oct;50(10):1644-50. doi: 10.1046/j.1532-5415.2002.50455.x.
PubMed 12366617Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, Muratore M, Casciaro S. Major osteoporotic fragility fractures: Risk factor updates and societal impact. World J Orthop. 2016 Mar 18;7(3):171-81. doi: 10.5312/wjo.v7.i3.171. eCollection 2016 Mar 18.
PubMed 27004165Dahlgren MK, Lambros AM, Smith RT, Sagar KA, El-Abboud C, Gruber SA. Clinical and cognitive improvement following full-spectrum, high-cannabidiol treatment for anxiety: open-label data from a two-stage, phase 2 clinical trial. Commun Med (Lond). 2022 Nov 2;2(1):139. doi: 10.1038/s43856-022-00202-8.
PubMed 36352103
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Bone Turnover Biomarkers, CB2 and TRPV1 Polymorphisms as Potential Preventive Data in Osteoporosis and Perception of Improvement in Quality of Life in Women With Chronic Pain Treated With Medicinal Cannabis
- ClinicalTrials.gov ID
- NCT07783295
- Acronym / sponsor ID
- ORION / UPM-BONE-RELIEF-01
- Conditions
- Chronic Pain, Fibromyalgia, Osteoporosis, Orofacial Pain
- Keywords
- medical cannabis, cannabidiol, tetrahydrocannabinol, bone turnover, CB1 receptor, CB2 receptor, TRPV1 receptor, Women
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Associação Pan-Americana Multidisciplinar de EndocanabinologiaUniversity, hospital or other
- Collaborators
- Mackenzie Presbiterian University, São Paulo, Brazil, Associação Brasileira de Cannabis Medicinal
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 24 Aug 2026 (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.
Chronic pain disproportionately affects women and may coexist with impaired bone health, particularly during midlife and after menopause. The endocannabinoid system is involved in pain modulation and bone homeostasis; however, clinical studies that integrate pain outcomes, bone-related biomarkers, genetic variants, and salivary endocannabinoids remain limited.This randomized, triple-masked, placebo-controlled crossover trial will evaluate the effects of a full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 on chronic pain in women aged 45 to 80 years with chronic pain refractory to conventional treatment. Eighty participants will be randomly assigned to one of two treatment sequences: full-spectrum cannabis extract followed by matching placebo, or matching placebo followed by full-spectrum cannabis extract. The treatment periods, washout interval, and visit schedule will follow the final approved protocol.The primary outcome is change in chronic pain intensity measured using the Visual Analog Scale. Secondary outcomes include quality of life, sleep quality, functional impact, bone health biomarkers, bone mineral density measured by dualenergy X-ray absorptiometry, salivary endocannabinoids, the association of CB and TRPV genetic variants with treatment response, and adverse events. The study aims to generate evidence on the clinical effects and biological correlates of medicinal cannabis therapy in women with chronic pain.
Detailed description
This is a randomized, triple-masked, placebo-controlled crossover clinical trial conducted in women aged 45 to 80 years with moderate to severe chronic pain that has persisted for at least 3 months and has not responded adequately to conventional pharmacological or non-pharmacological treatments. Participants will be randomlyallocated in permuted blocks to one of two treatments sequences. Sequence A will receive a full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during the first treatment period, followed by a protocol-defined washout interval and matching placebo during the second treatment period. Sequence B will receive matching placebo during the first treatment period, followed by the washout interval and the full-spectrum medicinal cannabis extract during the second treatment period. The study product will be administered orally as softgel capsules. The target daily dose is 25 milligrams of cannabidiol and 5 milligrams of tetrahydrocannabinol. Dose titration during the first 2 weeks of each active treatment period will follow the final approved protocol.Participants, care providers, investigators, and outcome assessors will remain masked to treatment assignment as operationally applicable. Randomization will use a computer-generated sequence with permuted blocks of 4 and allocation concealment through opaque, sealed envelopes. The product and matching placebo will be supplied in indistinguishable presentations.Clinical evaluations will include pain intensity, quality of life, functional impact, sleep quality, concomitant medications, adherence, and adverse events. Laboratory assessments will include safety tests, selected bone metabolism biomarkers, inflammatory markers, and oxidative stress biomarkers. Bone mineral density and body composition will be assessed using dualenergy X-ray absorptiometry at protocol-defined baseline and final visits. Genetic analysis will evaluate CB and TRPV variants. Salivary anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide will be quantified using liquid chromatography coupled with tandem mass spectrometry according to the final sample collection schedule.The primary efficacy analysis will compare pain outcomes across cannabis and placebo treatment periods while accounting for the crossover design. Secondary analyses will evaluate changes in patient-reported outcomes and biomarkers, treatment safety, and associations between genetic variants or salivary endocannabinoid profiles and treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomly assigned in a 1:1 ratio to one of two crossover sequences. Sequence A will receive full-spectrum cannabis extract during Period 1 and matching placebo during Period 2. Sequence B will receive matching placebo during Period 1 and full-spectrum cannabis extract during Period 2. The treatment periods will be separatedby a protocol-defined washout interval. Randomization will use computer-generated permuted blocks of 4 with allocation concealment through opaque, sealed envelopes.
| Arm | Type | Receives |
|---|---|---|
| Cannabis Extract Then Placebo | Experimental | Drug: Full-Spectrum Cannabis Extract 5:1 (CBD:THC)Participants receive oral full-spectrum cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during Treatment Period 1, followed by the protocol-defined washout interval and matching placebo during Treatment Period 2. |
| Placebo Then Cannabis Extract | Placebo comparator | Drug: Full-Spectrum Cannabis Extract 5:1 (CBD:THC)Participants receive matching placebo during Treatment Period 1, followed by the protocol-defined washout interval and oral full-spectrum cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1 during Treatment Period 2. |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female sex, age 45 to 80 years
- Moderate to severe chronic pain, defined as a pain score of at least 4 on a 0 to 10 Visual Analog Scale, persisting for more than 3 months
- Documented inadequate response to at least 2 classes of analgesic treatments or non-pharmacological treatments
- Willingness to abstain from smoked cannabis and non-study cannabinoid products during the study
- Ability to understand the informed consent form and study questionnaires
Key exclusion criteria (8 listed)
- Cognitive impairment that precludes understanding of the informed consent form or study questionnaires
- Uncontrolled psychiatric condition, including uncontrolled psychotic disorder or bipolar disorder
- Pregnancy, breastfeeding, or intention to become pregnant during the study
- Current use of medicinal cannabis, smoked cannabis, or other cannabinoid products
- Known hypersensitivity to cannabinoids or formulation excipients
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 |
|---|---|---|
| Full-Spectrum Cannabis Extract 5:1 (CBD:THC)Oral softgel capsule containing full-spectrum medicinal cannabis extract with a cannabidiol to tetrahydrocannabinol ratio of 5:1. The target daily dose is 25 milligrams of cannabidiol and 5 milligrams of tetrahydrocannabinol. Participants will receive the study product once daily in the evening, with gradual dose titration during the first 2 weeks of each active treatment period, according to the final approved protocol. The product will be administered for the duration of each protocol-defined active treatment period. | Drug | Cannabis Extract Then Placebo, Placebo Then Cannabis Extract |
Primary outcome
Change From Period Baseline in Chronic Pain Intensity on the Visual Analog Scale
Time frame: At the baseline and end of each treatment period, approximately 6 months per period.
Chronic pain intensity will be measured using a 0 to 10 Visual Analog Scale, where 0 indicates no pain and 10 indicates the worst imaginable pain. The baseline score will be the mean pain intensity reported over the preceding 7 days. A clinical response is defined as a reduction of at least 30 percent from the baseline score of the corresponding treatment period.
10 secondary outcomes
Change From Period Baseline in Sleep Quality on the Pittsburgh Sleep Quality Index.
Time frame: At baseline and at 3 and 6 Months each treatment period.
Change From Period Baseline in Health-Related Quality of Life on the 36-Item Short Form Survey.
Time frame: At baseline and at Months 3 and 6 of each treatment period.
Change From Period Baseline in Pain-Related Quality of Life on the WHOQOL-Pain Instrument.
Time frame: At baseline and at Months 3 and 6 of each treatment period.
Change From Period Baseline in Fibromyalgia Impact Questionnaire Score Among Participants With Fibromyalgia.
Time frame: At baseline and at Months 3 and 6 of each treatment period.
Change From Baseline in Bone Mineral Density Measured by Dual-Energy X-Ray Absorptiometry.
Time frame: At baseline and at the final study visit, approximately 12 months after enrollment.
Change From Period Baseline in Serum Bone Turnover Biomarkers.
Time frame: At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
Association of CB2 and TRPV1 Genetic Variants With Pain Treatment Response.
Time frame: Genotyping at baseline; association with pain response through the end of each treatment period, approximately 12 months.
Change From Baseline in Salivary Endocannabinoid Concentrations.
Time frame: Use the final collection schedule; do not submit this entry until the protocol is harmonized as baseline-only or serial sampling.
Number of Participants With Treatment-Emergent Adverse Events.
Time frame: From first study product administration through the end of each treatment period, approximately 6 months per period.
Change From Period Baseline in Hepatic and Renal Safety Laboratory Values.
Time frame: At baseline and at protocol-defined follow-up visits through final study completion, approximately 12 months.
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 26 Aug 2026.
- Background: PubMed 35986066Andreis K, Billingsley J, Naimi Shirazi K, Wager-Miller J, Johnson C, Bradshaw H, Straiker A. Cannabinoid CB1 receptors regulate salivation. Sci Rep. 2022 Aug 19;12(1):14182. doi: 10.1038/s41598-022-17987-2.
- Background: PubMed 34776851de Melo Reis RA, Isaac AR, Freitas HR, de Almeida MM, Schuck PF, Ferreira GC, Andrade-da-Costa BLDS, Trevenzoli IH. Quality of Life and a Surveillant Endocannabinoid System. Front Neurosci. 2021 Oct 28;15:747229. doi: 10.3389/fnins.2021.747229. eCollection 2021.
- Background: PubMed 16472333Cupini LM, Bari M, Battista N, Argiro G, Finazzi-Agro A, Calabresi P, Maccarrone M. Biochemical changes in endocannabinoid system are expressed in platelets of female but not male migraineurs. Cephalalgia. 2006 Mar;26(3):277-81. doi: 10.1111/j.1468-2982.2005.01031.x.
- Background: PubMed 28861491Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016 Jul 1;1(1):154-165. doi: 10.1089/can.2016.0009. eCollection 2016.
- Background: PubMed 18404144Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2008 Apr;29(2):192-200.
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- Individual participant dataSharing planned: No
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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.
Alethéia B P Barbosa, PhD principal investigator
Universidade Presbiteriana Mackenzie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Full-Spectrum Cannabis Extract 5:1 (CBD:THC) in people with Chronic Pain and Fibromyalgia, run by Associação Pan-Americana Multidisciplinar de Endocanabinologia at 1 site in Brazil.
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 6 inclusion and 8 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: opening soon, as of the sponsor's last update on 26 Aug 2026. 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 Brazil. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Alethéia B P Barbosa, PhD (+55 11 97247-1484, abpablos@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Period Baseline in Chronic Pain Intensity on the Visual Analog Scale (time frame: At the baseline and end of each treatment period, approximately 6 months per period.). 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 NCT07783295, which also lists 74 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 26 Aug 2026; AzTrials last refreshed its copy on 26 Oct 2026.