Clinical trial NCT04059978: Pain Response to Cannabidiol in Opioid-induced Hyperalgesia, Acute Nociceptive Pain and Allodynia By Using a Model Mimicking Acute Pain in Healthy Adults
Official title: Pain Response to Cannabidiol in Opioid-induced Hyperalgesia, Acute Nociceptive Pain and Allodynia By Using a Model Mimicking Acute Pain in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Nociceptive Pain
Hyperalgesia
Allodynia
Opioid-induced Hyperalgesia
Keywords: Cannabidiol
Remifentanil
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2019-08-16
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in hyperalgesia measured by the area under the curve (AUCHyper)
timeFrame: from minute 100 to minute 160 after termination of remifentanil infusion
Secondary outcomes:
measure: Change in pain response (NRS) measured by the area under the curve (AUCNRS)
timeFrame: from minute 70 to minute 90 during remifentanil infusion
measure: Change in hyperalgesia measured by the area under the curve (AUCHyper)
timeFrame: from minute 70 to minute 90 during remifentanil infusion
measure: Change in allodynia measured by the area under the curve (AUCAllo)
timeFrame: from minute 70 to minute 90 during remifentanil infusion
measure: Change in pain response (NRS) measured by the area under the curve (AUCNRS)
timeFrame: from minute 100 to minute 160 after termination of remifentanil infusion
measure: Change in allodynia measured by the area under the curve (AUCAllo)
timeFrame: from minute 100 to minute 160 after termination of remifentanil infusion
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department of Anaesthesiology, University Hospital of Basel (USB)
Study officials:
affiliation: Department of Anaesthesiology, University Hospital of Basel
name: Tobias Schneider, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dieterle M, Zurbriggen L, Mauermann E, Mercer-Chalmers-Bender K, Frei P, Ruppen W, Schneider T. Pain response to cannabidiol in opioid-induced hyperalgesia, acute nociceptive pain, and allodynia using a model mimicking acute pain in healthy adults in a randomized trial (CANAB II). Pain. 2022 Oct 1;163(10):1919-1928. doi: 10.1097/j.pain.0000000000002591. Epub 2022 Jan 24.