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

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Leiden University Medical Center

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.