Influence of Δ9-tetrahydrocannabinol (THC) on Oxycodone Induced Ventilatory Depression in Healthy Volunteers
Status:
Recruiting
Trial end date:
2023-06-01
Target enrollment:
Participant gender:
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).