Pain Response to Cannabidiol in Opioid-induced Hyperalgesia, Acute Nociceptive Pain and Allodynia By Using a Model Mimicking Acute Pain in Healthy Adults

Study Overview
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Brief Summary
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Prospective, randomized, placebo-controlled, double-blinded, crossover study to investigate the effect of cannabidiol (CBD) on remifentanil-induced hyperalgesia in healthy volunteers in a well-established acute pain model. Participants are randomized according to the order of the two treatments (CBD + Remifentanil or Placebo + Remifentanil).

Detailed Description
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Opioid-induced hyperalgesia (OIH) is a clinically often neglected, but well described phenomenon. OIH could also be shown for Remifentanil in an acute pain model. As CBD showed antihyperalgesic potential in the animal model, this brings up the question if CBD might be used to prevent or diminish OIH. Until today there are no studies investigating CBD as an adjunct to remifentanil or other opioids regarding the OIH. This is however of great clinical value because CBD with its possible antihyperalgesic effect on the OIH might be a worthful adjunct for opioid based anaesthesia and analgesia. Every participant will pass through two interventions with electrically induced pain (Koppert model). CBD will be applied orally at the beginning of the intervention. Pain, allodynia and hyperalgesia will be assessed and recorded every 10 min during the remifentanil infusion and afterwards.

Official Title
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Pain Response to Cannabidiol in Opioid-induced Hyperalgesia, Acute Nociceptive Pain and Allodynia By Using a Model Mimicking Acute Pain in Healthy Adults

Conditions
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Acute Nociceptive Pain, Hyperalgesia, Allodynia, Opioid-induced Hyperalgesia

Intervention / Treatment
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* Drug: CBD
* Drug: Placebo
* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 18.5 until 25 kg/m2 Able to give informed consent Exclusion Criteria: Regular consumption of cannabinoids or other drugs / substances Regular intake of medications potentially interfering with pain sensation (analgesics, antihistamines, calcium and potassium channel blockers, serotonin / noradrenaline reuptake inhibitors, corticosteroids) Neuropathy Chronic pain Neuromuscular disease Psychiatric disease Known or suspected kidney or liver disease Pregnancy (cf. 8.6 Trial specific preventive measures) / Lactation Allergy / hypersensitivity to cannabidiol Contraindications for Remifentanil (e.g. hypersensitivity)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CBD + Remifentanil<br>CBD 1600 mg p.o. + Remifentanil 0.1 µg/kg/min i.v. for 30 min | Drug: CBD<br>* 1600mg cannabidiol, single oral dose (8 ml oily solution)<br>Drug: Remifentanil<br>* Remifentanil 0.1 µg/kg/min i.v. for 30 min<br>|
| Placebo Comparator: Placebo + Remifentanil<br>Placebo p.o + Remifentanil 0.1 µg/kg/min i.v. for 30 min | Drug: Placebo<br>* Placebo p.o, single oral dose (8 ml oily solution)<br>Drug: Remifentanil<br>* Remifentanil 0.1 µg/kg/min i.v. for 30 min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hyperalgesia measured by the area under the curve (AUCHyper) | Change in hyperalgesia measured by the area under the curve (AUCHyper) | from minute 100 to minute 160 after termination of remifentanil infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain response (NRS) measured by the area under the curve (AUCNRS) | Change in pain response (NRS) measured by the area under the curve (AUCNRS) | from minute 70 to minute 90 during remifentanil infusion | 
| Change in hyperalgesia measured by the area under the curve (AUCHyper) | Change in hyperalgesia measured by the area under the curve (AUCHyper) | from minute 70 to minute 90 during remifentanil infusion | 
| Change in allodynia measured by the area under the curve (AUCAllo) | Change in allodynia measured by the area under the curve (AUCAllo) | from minute 70 to minute 90 during remifentanil infusion | 
| Change in pain response (NRS) measured by the area under the curve (AUCNRS) | Change in pain response (NRS) measured by the area under the curve (AUCNRS) | from minute 100 to minute 160 after termination of remifentanil infusion | 
| Change in allodynia measured by the area under the curve (AUCAllo) | Change in allodynia measured by the area under the curve (AUCAllo) | from minute 100 to minute 160 after termination of remifentanil infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabidiol, Remifentanil