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Research Paper

Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial

Vela, Jonathana,b,*; Dreyer, Lenea,b; Petersen, Kristian Kjærc; Arendt-Nielsen, Larsc; Duch, Kirsten Skjærbækd; Kristensen, Salomea,b

Author Information
doi: 10.1097/j.pain.0000000000002466

1. Introduction

Chronic musculoskeletal pain conditions are a major global burden and rank among the top 11 conditions of 328 diseases,44 adding to the global burden of pain.6

Medical cannabis has been suggested as a modulator of joint pain because of the possible anti-inflammatory and analgesic properties of phytocannabinoids as shown in animal studies.18,38 Yet, a systematic review of randomised controlled trials conducted in 2020 by the International Association for the Study of Pain (IASP) Presidential Task Force on cannabis and cannabinoid analgesia found sparse evidence of a beneficial effect in the trials performed to date.19 This lead to the conclusion that cannabinoids, based on the current available evidence, could not be recommended for pain management.34

One notable observation by the IASP Task Force was the lack of high-quality trials examining the analgesic properties of cannabidiol (CBD) without the addition of delta-9-Δ-tetrahydrocannabinol (THC).28

The mechanisms of action of CBD have not been fully elucidated. Cannabidiol could mediate its effects by acting as an antagonist of the 5-HT1A20,25,46 receptor, agonist of the transient receptor potential vanilloid family31 causing desensitization in a similar fashion to capsaicin, and adenosine A2A receptor agonist.33 Cannabidiol is generally well tolerated in clinical trials41 and considered nonintoxicating,27 although sedation can occur at higher doses.39 However, long-term effects and safety of cannabinoid treatments have not been studied.21

In a recent meta-analysis of 17 preclinical trials with different pain models, a small yet significant effect was found for CBD with a standardised mean difference of 1.12 (95% confidence interval [CI] 0.84-1.40)38 with the greatest effect seen in neuropathic pain models (nerve injury, chemotherapy, and diabetes) and conflicting results in inflammatory pain models (formalin, Freund adjuvant, and carrageenan) and osteoarthritis.18

Van de donk et al. performed a randomized controlled crossover trial15 exploring the effects of a single dose of cannabis medication (18.8 mg CBD, less than 1 mg THC) in patients with fibromyalgia but this combination had no effect on pressure pain threshold or patient-reported pain. Likewise, Bebee et al. performed a randomized controlled trial2 exploring the effects of a single dose 400 mg CBD in patients admitted to the emergency department for acute low back pain and found no effect on pain intensity 2 hours after administration when compared with a placebo. Despite a paucity of clinical evidence, CBD is currently used for pain conditions as is evident from a web-based survey of CBD users from 2018 which showed that 62% of respondents reported using CBD for medical conditions with chronic pain and arthritis or joint pain as the main reasons.12

Thus, at present, CBD is being introduced as medicine worldwide with a lack of evidence for its effect. This necessitates investigation of CBD including dosing regimens and treatment efficacy in different pain conditions in high-quality studies as recently suggested.21

The aim of this single-centre randomized double-blind placebo-controlled trial was to investigate the analgesic effect and safety of 12-week administration of synthetic CBD as an add-on treatment to conventional pain management in patients with hand osteoarthritis (Hand-OA) and psoriatic arthritis (PsA).

2. Methods

2.1. Design

The trial (NordCAN) was designed as a single-centre, double-blind, randomized and placebo-controlled trial conducted at the Rheumatological Research Unit at the Department of Rheumatology, Aalborg University Hospital, Denmark. The trial was approved by the Danish Human Ethics Committee (N-20170074), the Danish Medicines Agency (2017091784), and the Danish Data Protection Agency (2017-245). The NordCAN project was registered on ClinicalTrials.gov (NTC03693833) and in the European Clinical Trials database (2017-003574-13). The trial was continually monitored by the Good Clinical Practice (GCP) unit of Aalborg University Hospital, externally audited by the Danish Medicine Agency, and was conducted in accordance with the Declaration of Helsinki, GCP, and Danish regulatory requirements.

2.2. Patients and participants

Patients with PsA or Hand-OA were included between November 2018 and September 2020 after obtaining written informed consent. Inclusion criteria were fulfilling the 2006 Classification Criteria for Psoriatic Arthritis42 or the 1990 American College of Rheumatology criteria,1 pain intensity during the past 24 hours measured by a visual analogue scale (VAS) ≥30/100 mm at inclusion, age ≥18 years, and an ability and willingness to give written informed consent and to meet the requirements of the trial protocol. Exclusion criteria included concurrent diagnosis of chronic regional pain syndrome or neuropathy, other known diseases where exacerbations needed to be treated with systemic corticosteroids (ie, certain types of inflammatory bowel disease) or patients who have received systemic corticosteroid treatment during the past 3 months, concurrent diagnosis of other inflammatory joint diseases, eg, rheumatoid arthritis or ankylosing spondylitis, and patients with gout if their disease had not been in remission for more than 6 months. Concurrent active malignant disease; planned major surgery during the intervention period or recent major surgery; current or planned pregnancy during the trial period; known allergy or contraindication to CBD treatment; previous addictive behaviour defined as abuse of cannabis, opioids, or other recreational or pharmaceutical drugs; severely decreased liver function; kidney function or known chronic heart failure; history of epilepsy; or severe cramps were also exclusion criteria.

2.3. Intervention

The active synthetic CBD 10 mg tablet and placebo tablet (containing the same ingredients except CBD) were produced by Glostrup Pharmacy (Glostrup, Denmark).

Patients initially received either oral CBD 10 mg or a placebo tablet once daily with the dose increased to 10 mg twice daily after 2 weeks. Patients were contacted by the investigator after 4 weeks, and those not experiencing a pain reduction of more than 20 mm on the VAS had their dose increased to 10 mg thrice daily until the end of treatment period. Patients were advised to take the trial medication together with meals to ensure optimal uptake4 and were also encouraged to keep their usual analgesic regimen. Changes in a disease-modifying antirheumatic drug regimen in patients with PsA led to discontinuation from the trial.

2.4. Randomisation procedure and allocation concealment

The randomisation sequence was computer generated by a trial pharmacist from Glostrup Pharmacy, who had no clinical involvement in the trial. Patients who met the eligibility criteria were randomized to receive either CBD or placebo in predefined blocks of 8, 16, and 24. Stratification was based on disease (PsA or Hand-OA), and allocation was concealed from patients and investigators.

2.5. Outcomes measures

The primary outcome was the difference between groups in the change of patient-reported pain intensity during the past 24 hours on VAS after 12 weeks of treatment (ΔVAS-pain). This was assessed using a paper-based 100-mm VAS accompanied with the text “How much pain have you experienced in the most symptomatic joint during the last 24 hours,” with 0 signifying no pain and 100 signifying worst pain imaginable.

Safety outcomes included percentage of patients experiencing adverse events (AEs) and a characterization of serious AEs (SAEs).

Explorative outcomes included assessment of anxiety and depression quantified using the Hospital Anxiety and Depression Scale (HADS)48 providing a score of 0 to 21 for each domain, where higher scores equal greater involvement of either anxiety or depression.

Subjective assessment of sleep quality was quantified using the Pittsburgh Sleep Quality Index (PSQI). Scores ranging from 0 to 21, where 21 indicates severe difficulties in all sleep-related areas.8

Pain-specific catastrophizing was quantified using the Pain Catastrophizing Scale (PCS) scored from 0 to 52, with 52 indicating the highest levels of catastrophizing.40 Disability was assessed using the Health Assessment Questionnaire Disability Index43 scale ranging from 0 to 3, with 3 indicating maximal disability. Pretreatment expectancy was quantified using the Stanford Expectation of Treatment Scale47 quantifying both positive and negative expectations of treatment on a scale from 0 to 21 were 21 indicates maximal positive or negative expectation.

2.6. Clinical laboratory tests

Blood samples were collected as part of routine laboratory tests performed on patients. The analysis panel included C-reactive protein, creatinine, and alanine aminotransferase.

2.7. Power and sample size considerations

Sample size calculation was performed with the following assumptions: alpha = 0.05, power = 80%, and standard deviations for pain intensity for Hand-OA and PsA at 30 mm. Detecting a difference of 15 mm in a 2-sample, 2-tailed t test would require a sample of 65 patients in each group.

2.8. Statistical analysis

Baseline variables were described for all participants with means and SDs or medians and interquartile ranges (IQRs) for continuous variables according to sample distribution. Discrete variables were reported with count and percentages.

Normality of the variable's sample distribution was assessed visually by the Q-Q plot.

The efficacy analysis was based on the data from the full-analysis set, ie, the intention-to-treat population, including all participants who were randomised, assessed at baseline, and received at least one dose of trial medication.

The safety analysis includes all patients who were randomly assigned to a trial group and have had exposure to the trial drug or placebo.

Sensitivity analysis included stratification based on disease (PsA or Hand-OA). Furthermore, the following post hoc analyses were performed; a between-group comparison of the number of patients achieving more than 30-mm reduction in pain intensity, 30% reduction in pain intensity, and 50% reduction in pain intensity.

Differences in continuous outcomes between groups were compared using an independent 2-sided t test for normal distributed variables and the bootstrap t test with 10,000 replicates for continuous nonnormally distributed variables.16 In addition, confidence intervals were created using bootstrap for nonnormal distributed variables. Discrete variables were compared using a χ2 test. Differences were considered significant with a P value of < 0.05.

All data management and analyses were performed using R version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria).

3. Results

3.1. Subjects

One hundred fifty-two patients were screened, and 136 patients (59 with PsA and 77 with Hand-OA) were randomized to either CBD or placebo. Two participants in the CBD group withdrew because of personal reasons. Two participants in the placebo group withdrew because of side effects: one with gastrointestinal distress and one with an allergic reaction. Two participants in the placebo group underwent surgery unrelated to the trial and withdrew. One participant had rheumatoid arthritis which was misdiagnosed as Hand-OA (Fig. 1). For baseline demographics, refer to Table 1. Few patients used opioids as concomitant analgesic medication in both groups, 2.8% in the CBD group vs 3.0% in the placebo group (P > 0.99). For concomitant analgesic medicine, refer to Table 2.

F1
Figure 1.:
CONSORT diagram. CBD, cannabidiol.
Table 1 - Baseline parameters.
CBD Placebo
N 70 66
Age, y median [IQR] 62.00 [56.25 to 68.00] 61.50 [53.00 to 70.75]
Women, n (%) 42 (60.0) 46 (70.0)
BMI, (kg/m2) median [IQR] 26.99 [23.86 to 31.16] 26.25 [23.03 to 29.72]
Pack-y, median [IQR] 1 [0 to 15] 0 [0 to 16.50]
PsA, n (%) 31 (44) 28 (42)
Hand-OA, n (%) 39 (56) 38 (58)
Pain VAS, mm median [IQR] 52.00 [40.50 to 70.70] 61.00 [43.20 to 73.50]
HAQ-DI, median [IQR] 0.62 [0.25 to 0.88] 0.88 [0.50 to 1.50]
HADS depression, median [IQR] 2 [1 to 4] 2.50 [1 to 5]
HADS anxiety, median [IQR] 5 [2 to 7] 5 [2 to 8]
PSQI, median [IQR] 7.00 [5.00 to 11.00] 10.00 [6.00 to 12.00]
PCS, median [IQR] 16.00 [11.00 to 21.00] 15.00 [11.00 to 24.75]
Pretreatment expectancy (SETS)
 Positive expectancy score [IQR] 17.00 [14.25 to 18.00] 16.00 [14.00 to 19.00]
 Negative expectancy score [IQR] 11.00 [9.00 to 13.75] 10.00 [8.00 to 12.00]
 Previous CBD use, n (%) 10 (14) 15 (23)
Serology
 CRP, mg/L, median [IQR] 2.20 [0.90 to 4.90] 2.90 [1.30 to 4.30]
 Alanine aminotransferase U/L, median [IQR] 22.00 [18.00 to 30.00] 25.00 [18.00 to 32.00]
 Creatinine, mean umol/L, (SD) 70.16 (13.87) 70.25 (16.71)
BMI, body mass index; CBD, cannabidiol; CRP, C-reactive protein; HADS, Hospital Anxiety and Depression Scale; Hand-OA, hand osteoarthritis; HAQ-DI, Health Assessment Questionnaire Disability Index; IQR, interquartile range; PCS, Pain Catastrophizing Scale; PsA, psoriatic arthritis; PSQI, Pittsburgh Sleep Quality Index; SETS, Stanford Expectations of Treatment Scale; VAS, visual analogue scale.

Table 2 - Concomitant analgesic medicine.
CBD Placebo
N 70 66
Paracetamol, n (%) 55 (78.6) 47 (71.2)
NSAIDs, n (%) 28 (40.0) 27 (40.9)
Antiepileptics, n (%) 5 (7.1) 11 (16.7)
Codeine, n (%) 3 (4.3) 2 (3.0)
Tramadol, n (%) 5 (7.1) 8 (12.1)
Opioids, n (%) 2 (2.8) 2 (3.0)
None, n (%) 12 (17.1) 8 (12.1)
CBD, cannabidiol; NSAID, nonsteroidal anti-inflammatory drug.

When asked which intervention they received, a greater number in the placebo group guessed correctly compared with the CBD group (61% vs 22%). The number of patients receiving 20 mg at the end of the study was 17 (25%) in the CBD group vs 17 (27.9%) in the placebo group (P = 0.866).

3.2. Primary outcome

No statistically significant differences in pain intensity were found between the CBD group and placebo group at 12 weeks for the intention-to-treat analysis with a mean difference of 0.23 mm (95% CI −9.41 to 9.90; P = 0.96) on a 0 to 100-mm scale. A statistically significant reduction from baseline in pain intensity was found for both CBD (11.68 mm; 95% CI 5.33 to 18.0; P < 0.001) and placebo (11.45 mm; 95% CI 0.51-1.78; P = 0.001).

A sensitivity analysis based on disease showed similarly effect of CBD for the PsA group (between-group difference of 4.48 with 95% CI −17.44 to 8.49; P = 0.49) and Hand-OA (between-group difference of 2.94 with 95% CI −10.03 to 15.92; P = 0.65).

Fifteen patients (22%) in the CBD group experienced a reduction in pain intensity of more than 30 mm vs 13 patients (21%) in the placebo group (P > 0.99).

A reduction of pain intensity of more than 30% was experienced by 27 (40%) and 24 (40%) in the CBD group and placebo group, respectively (P > 0.99). A reduction of pain intensity of more than 50% was experienced by 17 (25%) and 16 (27%) in the CBD group and placebo group, respectively (P = 0.99).

3.3. Explorative outcomes

The CBD group demonstrated a significant decrease from baseline in the Health Assessment Questionnaire score of 0.13 (95% CI 0.04-0.22; P < 0.01) and a decreased PCS score of 3.55 (95% CI 1.90-5.34 P < 0.001) while the placebo group experienced a reduction in the PCS score of 2.48 (95% CI 0.20-4.76; P = 0.03). However, no significant group differences between the 2 groups were found in any of the explorative outcomes (Table 3).

Table 3 - Outcomes after 12 weeks
CBD Placebo Between-group difference P
Change Change
Primary outcome
 Pain VAS, mm 11.68 (5.33 to 18.0)* 11.45 (5.01 to 18.15)* 0.23 (−9.41 to 9.90) 0.96
Explorative outcomes
 HAQ-DI 0.13 (0.04 to 0.22)* 0.10 (−0.02 to 0.21) 0.03 (−0.11 to 0.18) 0.65
 PSQI 0.13 (−0.7 to 0.83) 0.84 (−0.28 to 1.96) −0.71 (−1.99 to 0.55) 0.27
 HADS-depression 0 (−0.59 to 0.57) 0.04 (−0.42 to 0.52) −0.04 (−0.79 to 0.70) 0.92
 HADS-anxiety 0.07 (−0.63 to 0.69) 0.59 (−0.16 to 1.35) −0.69 (−0.41 to 2.75) 0.14
 PCS 3.55 (1.90 to 5.34)* 2.48 (0.20 to 4.76)* 1.07 (−1.73 to 3.88) 0.46
*P < 0.05.
Means and confidence intervals calculated using the bootstrap t test.
CBD, cannabidiol; HADS, Hospital Anxiety and Depression Scale; HAQ-DI, Health Assessment Questionnaire Disability Index; PCS, Pain Catastrophizing Scale; PSQI, Pittsburgh Sleep Quality Index; VAS, visual analogue scale.

3.4. Adverse events

A total of 4 SAEs were reported during the 12-week trial period. In the CBD group, 1 participant was diagnosed with ductal carcinoma and 1 participant with lipothymia requiring observation in the emergency department. In the placebo group, 1 patient experienced an acute shoulder fracture and 1 patient required observation in the emergency department because of malignant hypertension. None of the SAEs were deemed adverse drug reactions by the trial group.

A total of 59 patients (33 in the CBD group and 26 in the placebo group) experienced a total of 119 AEs. Patients in the CBD group experienced more AEs related to the ear–nose–throat region with 8 events vs 0 in the placebo group, and AEs related to the skin with 3 events in the CBD group vs 0 in the placebo group (Table 4).

Table 4 - Serious adverse events and adverse events.
CBD, no. (%) (N = 58) Placebo, no. (%) (N = 61)
Serious adverse events
 Overall 2 2
 Deaths 0 0
Adverse events
 Musculoskeletal 11 (19) 11 (18)
 Lower gastrointestinal 2 (4) 9 (15)
 Mood 4 (7) 3 (5)
 Urogenital 0 (0) 5 (8)
 Upper gastrointestinal 6 (10) 10 (16)
 Airways 7 (12) 6 (10)
 Ear–nose–throat 8 (14) 0 (0)
 Dermal 3 (5) 0 (0)
 Cardiovascular 4 (7) 4 (7)
 Others 13 (22) 13 (21)
CBD, cannabidiol.

4. Discussion

To the best of our knowledge, this trial is the first randomised placebo-controlled trial investigating the effect of pure CBD as an add-on analgesic therapy in patients with joint disease. The main finding was that 12 weeks of CBD treatment did not demonstrate significant clinical analgesic effects in patients with Hand-OA or PsA and pain of at least moderate intensity.

Sensitivity analysis based on the number of patients experiencing a reduction of ≥30 mm pain intensity and the number of patients experiencing a reduction of pain intensity of ≥30% or ≥50% gave similar results.

These findings are similar to 2 recent RCTs examining the short-term (2-hour follow-up) analgesic effects of a single dose of CBD were no significant difference between placebo was seen.2,14 Our results contradict 2 small previous trials13,45 investigating CBD as an analgesic therapy. However, in both studies the patients were treated with a mix of CBD and THC (up to 50%). In a randomized controlled trial, Wade et al.45 studied the effect of a CBD-rich cannabis extract on pain intensity in 12 patients with painful neurological disorders, and a statistically significant decrease in pain intensity in the CBD group compared with placebo was observed, but they did not disclose the amount of THC in the extract and patients were allowed to use THC-rich rescue medication. An uncontrolled trial assessed 7 patients with kidney transplant receiving 300-mg CBD and reported an analgesic effect in 4 of 7 patients.13 The authors did not explain how pain was quantified, and the CBD solution used had a CBD to THC ratio of 30:1 that resulted in a THC dose of 10 mg which could be intoxicating with psychotropic side effects.27

4.1. Explorative outcomes

Poor sleep quality, anxiety, and depression have previously been linked to clinical pain intensity outcomes.26 Although CBD is used as a sleep aid, the evidence for this claim is currently lacking. This trial found no difference in PSQI scores comparing the placebo and CBD groups. This is in line with a previous case series of 72 patients (1/3 complained of sleep disorder) were treatment with 25 to 150-mg CBD daily did not improve PSQI scores after 3 months of treatment.37

Results from preclinical trials suggests that CBD could have antidepressant properties, but only a single clinical trial has included a depression score in patients without neurological disease or cannabis abuse disorder and found no difference between CBD and placebo.24 In this trial, we used the HADS to identify signs of depression or anxiety. Patients had low median depression scores at baseline (median 2; IQR 1-5), and CBD treatment did not reduce the HADS depression score.

Cannabidiol has been extensively examined as an anxiolytic drug,32 and most studies are single-dose trials performed during a speaking performance. These show inconsistent efficacy for dose and time of effect.3,26,49 As with HADS depression, patients in this study had low median anxiety scores at baseline (CBD: 5; IQR 2-7 and placebo 5; IQR 2-8) and CBD treatment did not reduce the HADS anxiety score.

Bjelland et al. found the optimal cut-off values to detect psychiatric morbidity cases to be >7 for anxiety and >9 for depression, both of which are above the upper limit of baseline IQR values in the CBD group.5 Further trials with patients with comorbid anxiety or depression are needed to determine whether an anxiolytic or antidepressive effect exists.

4.2. Adverse events and side effects

In this trial, 2 patients in the CBD group experienced SAEs. One patient experienced an episode of lipothymia which was deemed to be due to an underlying medical condition, and 1 patient was diagnosed with a ductal carcinoma in situ after a few weeks of treatment, and hence, this was most likely not related to the treatment. Except for one possible case in the placebo group, no participants experienced any obvious allergic reactions. A review of SAEs in 18 randomised trials testing pure CBD found the occurrences of SAEs to be low. The highest proportion of SAEs occurred in epilepsy trials with concomitant use of different antiepileptic drugs and CBD doses greater than 300 mg daily.36 A review of AEs in 13 randomised trials found greater odds of decreased appetite, diarrhea, sedation, and somnolence in participants treated with CBD. When excluding studies with patients with epilepsy only diarrhea was found to be a significant side effect with odds ratio 2.61 (1.07-4.64). The mean dose in nonepilepsy studies was 900 mg/d.10

4.3. Pain intensity measurement

Patients of rheumatology outpatient clinics in Denmark register pain intensity at each visit in the nation-wide DANBIO register through the 100-mm VAS during the past 24 hours. This was chosen as the primary outcome because patients and clinicians are accustomed with this measure and our group have consistently used VAS during the past 24 hours in our studies of osteoarthritis.29,30

4.4. Limitations

Because of a lack of trials investigating optimal CBD doses for an analgesic effect, we choose a pragmatic dose of 20 to 30 mg daily based on recommendations from patient surveys and usage in similar trials.7,9,23 This dose could prove insufficient to produce the plasma concentrations required to activate relevant receptors involved in inflammation and nociception.9 Cannabidiol dosage regimens used in trials regarding neurological disease often surpass 1000 mg daily but with a significant number of side effects.10 Future high-quality, double-blind, randomized and placebo-controlled trials are needed to further explore the possible analgesic properties of higher doses of CBD. Furthermore, patients were encouraged to adhere to their usual analgesic regimen during the trial but were not required to keep a diary of daily analgesic use or use of the trial intervention. We found no association between CBD and SAEs, but this trial was insufficiently powered to detect rare AEs.

We investigated synthetic CBD in a “single-ingredient” setting allowing for examination of CBD without the presence of other cannabinoids (including THC), terpenes, and flavonoids because these could, in theory, modify the therapeutic effect of CBD. This phenomenon has been dubbed the “entourage effect,” which is a proposed synergistic effect35 between different components of the cannabis plant, but evidence supporting this effect is conflicting,17,22 and clinical trials examining the entourage effect are currently lacking.11 Still, generalisability of our results regarding other CBD formulations should be performed with consideration.

Strengths of this trial were the randomized, double-blind, placebo-controlled design and the large number of participants which is in accordance with recommendations by the IASP.21

5. Conclusion

This is the first large, randomized placebo-controlled trial examining the effect of CBD on pain intensity in patients with chronic pain of at least moderate intensity. The current trial found neither clinically nor statistically significant effects of 20 to 30 mg/day CBD for 12 weeks on pain intensity in patients with Hand-OA and PsA when compared with placebo. In addition, no statistically significant effects were found on sleep quality, signs of depression, anxiety, or pain catastrophizing when comparing CBD with placebo. Studies investigating higher doses of CBD and assessing different pain disorders are needed.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Data are available on reasonable request from the corresponding author.

Appendix A. Supplemental digital content

Supplemental digital content associated with this article can be found online at https://links.lww.com/PAIN/B480.

Supplemental video content

A video abstract associated with this article can be found at https://links.lww.com/PAIN/B480.

Acknowledgements

The authors acknowledge biomedical laboratory scientists Charlotte Mose Skov and Dorte Emilie Wulff for technical help with blood samples and pharmacist Kristian Østergaard Nielsen with supplying the investigational product.

Author contributions: J. Vela was the primary contributor to the conception and design of the protocol and J. Vela is responsible for drafting of the manuscript. S. Kristensen, K.K. Petersen, L. Dreyer, K.S. Duch, and L. Arendt Nielsen contributed to the conception and design of the trial. S. Kristensen, K.K. Petersen, L. Dreyer, K.S. Duch, and L. Arendt Nielsen have contributed substantially during manuscript revision and approval of the final draft.

This work was supported by the Danish Psoriasis Foundation Grant number 210417, the Danish Rheumatism Foundation Grant number R179-A6299, and Aalborg University and Aalborg University hospital (2016-017615). Centre for Neuroplasticity and Pain (CNAP) is supported by the Danish National Research Foundation (DNRF121).

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Keywords:

Cannabidiol; Joint pain; Psoriatic arthritis; Hand osteoarthritis; Medical cannabis

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