Influence of Δ9-tetrahydrocannabinol (THC) on Oxycodone Induced Ventilatory Depression in Healthy Volunteers

NCT05235503 | Unknown Phase 4

• 3 other identifiers: P21.0302021-000083-29NL76443.058.21
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Opioid misuse and abuse are common problems in the Western world. The rate of unintentional drug overdose is rapidly increasing, not only in the Unites States but also in the Netherlands. Additionally, it is well known that opioids are often used (and abused) in combination with other legal or illicit substances, for example cannabis, including medicinal (i.e. doctor prescribed) cannabis. A major opioid-induced adverse effect is respiratory depression and there are no data that show how oxycodone interacts with cannabis on the ventilatory control system. An appreciable effect is possible given the sedative effects of cannabis. Moreover, investigators previously showed that combining even a low dose of oxycodone (20 mg) with ethanol increased the likelihood of an apneic event (van der Schrier et al. Anesthesiology 2017; 102: 115-122). Because of this side effect and also due to the rising number of addicted chronic opioid users, there is an increasing imminent societal, political and medical interest in advancing research on opioids, opioid-drug interaction and alternatives for the treatment of various chronic illnesses and chronic pain. Hypothesis: The investigators hypothesize that cannabis will amplify the ventilatory depressant effect of oxycodone (primary end-point). Objective: The objective of the study is to quantify the interactive effect of Δ9-tetrahydrocannabinol (THC) and oxycodone on ventilatory control. Study design: Double blind, randomized cross-over, placebo-controlled design. Study population: Healthy human volunteers between the age of 18 and 45 years old. Intervention: Visit A: placebo capsule at t = 0 min + Bedrocan (22.4 mg THC) at t = 90 and 270 min; Visit B: oxycodone 20 mg at t = 0 min + Bedrocan (22.4 mg THC) at t = 90 and 270 min. Main study parameters/endpoints: Primary endpoint: The effect of inhaled THC on ventilation at an end-tidal PCO2 = 55 mmHg without and with concomitant intake of 20 mg oxycodone immediate release (IR) capsule in healthy volunteers 120 min after oxycodone intake. Secondary endpoints: (1) Outcome of Bowdle and Bond \& Lader questionnaires; (2) Level of sedation; (3) Pain Pressure Threshold; (4) slope of the hypercapnic ventilatory response; (5) plasma concentrations of THC, 11-OH-THC and oxycodone; a secondary analysis will be performed on the pharmacokinetic and pharmacodynamic data (PKPD modeling).

Conditions

Respiratory Depression; Cannabis Use; Opioid Use

Outcome Measures

Primary Outcomes (1)

• The effect of inhaled THC on ventilation (Liters per minute) at an end-tidal PCO2 = 55 mmHG without and with concomitant intake of 20 mg oxycodone immediate release (IR) capsule in healthy volunteers 120 min after oxycodone intake.

  As stated above

  120 minutes after oxycodone intake

Secondary Outcomes (5)

• Bowdle questionnaire score;

  Time 0, 30, 90, 150, 210, 270, 330, 390 and 450 minutes after oxycodon or placebo administration.

• Pain Pressure Threshold (mN);

  Time 0, 25, 55, 90, 105, 125, 145, 205, 265, 270, 285, 305, 325, 385 and 445 minutes after oxycodon or placebo administration.

• slope of the hypercapnic ventilatory response;

  Time 0, 60, 120, 180, 240, 300, 360 and 420 minutes after oxycodon or placebo administration.

• plasma concentrations of THC, 11-OH-THC and oxycodone; a secondary analysis will be performed on the pharmacokinetic and pharmacodynamic data (PKPD modeling).

  Time 0, 30, 60, 95, 110, 130, 150, 210, 270, 275, 290, 310, 330, 390 and 450 minutes after oxycodon or placebo administration.

• Bond & Lader questionnaire score

  Time 0, 30, 90, 150, 210, 270, 330, 390 and 450 minutes after oxycodon or placebo administration.

Study Arms (2)

20mg Oxycodon (capsule) + 100 mg Bedrocan (vaporized)

EXPERIMENTAL

As stated above

Drug: Medicinal cannabis in combination with oxycodon

Placebo oxycodon (capsule) + 100 mg Bedrocan (vaporized)

PLACEBO COMPARATOR

As stated above

Drug: Medicinal cannabis in combination with placebo oxycodon

Interventions

Medicinal cannabis in combination with oxycodon DRUG

The intervention will be administering the combination of medicinal cannabis in combination with oxycodon

20mg Oxycodon (capsule) + 100 mg Bedrocan (vaporized)

Medicinal cannabis in combination with placebo oxycodon DRUG

The intervention will be administering the combination of medicinal cannabis in combination with placebo oxycodon

Placebo oxycodon (capsule) + 100 mg Bedrocan (vaporized)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• aged 18-45 years,
• body mass index \< 30 kg.m-2,
• able to understand the written informed consent form,
• able to communicate with the staff,
• able and willing to complete the study procedures,
• signed the informed consent form,
• deemed suitable by the investigators.

You may not qualify if:

• Presence or history of any medical or psychiatric disease (incl. a history of substance abuse, anxiety, or the presence of a painful syndrome such as fibromyalgia);
• Use of any medication in the three months prior to the study (incl. paracetamol or other pain killers), except for oral contraceptives (females);
• Use of more than 21 alcohol units per week;
• Use of cannabis in the 4 weeks prior to the study;
• A positive urinary drug test or a breath alcohol test at screening or on the morning of the experiment;
• Pregnancy, lactating or a positive pregnancy test on the morning of the experiment;
• Participation in another drug trial in the 60 days prior to dosing.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Medical Marijuana

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Monique van Velzen, Phd

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cornelis Jan CJ van Dam, MSc

CONTACT

+31715299797; c.j.van_dam@lumc.nl

Monique van Velzen, Phd

CONTACT

+31715262301; m.van_velzen@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Blinding via pharmacy
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Coordinating investigator

Model Details: Double blind, randomized cross-over, placebo-controlled design.

Study Record Dates

• First Submitted: November 30, 2021
• First Posted: February 11, 2022
• Study Start: December 9, 2021
• Primary Completion: December 1, 2022
• Study Completion: June 1, 2023
• Last Updated: February 11, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)