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

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Completed

CT.gov ID

NCT04059978

Collaborator

(none)

Enrollment

Location

Arms

4.7

Actual Duration (Months)

4.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Nociceptive Pain Hyperalgesia Allodynia Opioid-induced Hyperalgesia	Drug: CBD Drug: Placebo Drug: Remifentanil	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

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

Actual Study Start Date :

May 26, 2020

Actual Primary Completion Date :

Oct 15, 2020

Actual Study Completion Date :

Oct 15, 2020

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: CBD + Remifentanil

CBD 1600 mg p.o. + Remifentanil 0.1 µg/kg/min i.v. for 30 min

Drug: CBD

1600mg cannabidiol, single oral dose (8 ml oily solution)

Drug: Remifentanil

Remifentanil 0.1 µg/kg/min i.v. for 30 min

Placebo Comparator: Placebo + Remifentanil

Placebo p.o + Remifentanil 0.1 µg/kg/min i.v. for 30 min

Drug: Placebo

Placebo p.o, single oral dose (8 ml oily solution)

Drug: Remifentanil

Remifentanil 0.1 µg/kg/min i.v. for 30 min

Outcome Measures

Primary Outcome Measures

Change in hyperalgesia measured by the area under the curve (AUCHyper) [from minute 100 to minute 160 after termination of remifentanil infusion]
Change in hyperalgesia measured by the area under the curve (AUCHyper)

Secondary Outcome Measures

Change in pain response (NRS) measured by the area under the curve (AUCNRS) [from minute 70 to minute 90 during remifentanil infusion]
Change in pain response (NRS) measured by the area under the curve (AUCNRS)
Change in hyperalgesia measured by the area under the curve (AUCHyper) [from minute 70 to minute 90 during remifentanil infusion]
Change in hyperalgesia measured by the area under the curve (AUCHyper)
Change in allodynia measured by the area under the curve (AUCAllo) [from minute 70 to minute 90 during remifentanil infusion]
Change in allodynia measured by the area under the curve (AUCAllo)
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 pain response (NRS) measured by the area under the curve (AUCNRS)
Change in allodynia measured by the area under the curve (AUCAllo) [from minute 100 to minute 160 after termination of remifentanil infusion]
Change in allodynia measured by the area under the curve (AUCAllo)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)