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

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ClinicalTrials.gov Identifier: NCT05235503
Recruitment Status : Recruiting
First Posted : February 11, 2022
Last Update Posted : February 11, 2022
Sponsor:
Information provided by (Responsible Party):
Albert Dahan, Leiden University Medical Center

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).


Condition or disease Intervention/treatment Phase
Respiratory Depression Cannabis Use Opioid Use Drug: Medicinal cannabis in combination with oxycodon Drug: Medicinal cannabis in combination with placebo oxycodon Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double blind, randomized cross-over, placebo-controlled design.
Masking: Double (Participant, Investigator)
Masking Description: Blinding via pharmacy
Primary Purpose: Other
Official Title: Influence of Δ9-tetrahydrocannabinol (THC) on Oxycodone Induced Ventilatory Depression in Healthy Volunteers
Actual Study Start Date : December 9, 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Marijuana

Arm Intervention/treatment
Experimental: 20mg Oxycodon (capsule) + 100 mg Bedrocan (vaporized)
As stated above
Drug: Medicinal cannabis in combination with oxycodon
The intervention will be administering the combination of medicinal cannabis in combination with oxycodon

Placebo Comparator: Placebo oxycodon (capsule) + 100 mg Bedrocan (vaporized)
As stated above
Drug: Medicinal cannabis in combination with placebo oxycodon
The intervention will be administering the combination of medicinal cannabis in combination with placebo oxycodon




Primary Outcome Measures :
  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. [ Time Frame: 120 minutes after oxycodone intake ]
    As stated above


Secondary Outcome Measures :
  1. Bowdle questionnaire score; [ Time Frame: Time 0, 30, 90, 150, 210, 270, 330, 390 and 450 minutes after oxycodon or placebo administration. ]
    Three factors of psychedelic effects can be derived from the Bowdle questionnaire: drug high, internal perception, and external perception. Internal perception reflects inner feelings that do not correspond with the reality and is derived from questions regarding the hearing of unrealistic voices or sounds and having unrealistic thoughts and paranoid or anxious feelings. The external perception indicates a misperception of an external stimulus or change in the awareness of the subject's surroundings and is derived from questions regarding the change of body parts, the change of surroundings, the altered passing of time, the difficulty of controlling thoughts, and the change in color and sound intensity.

  2. Pain Pressure Threshold (mN); [ Time Frame: Time 0, 25, 55, 90, 105, 125, 145, 205, 265, 270, 285, 305, 325, 385 and 445 minutes after oxycodon or placebo administration. ]
    We will use the FPN 100 N Algometer (FDN 100, Wagner Instruments Inc., Greenwich, CT, USA; Rolke et al., 2005) to deliver pressure pain on a skin area of 1 cm2 between thumb and index finger. The FDN 100 has a force capacity (± accuracy) of 100 ± 2 N (10 ± 0.2 kgf) and graduation of 1 N (100 gf), respectively. A gradually increasing pressure is manually applied and the subjects are asked to indicate when the procedure becomes painful (pressure pain threshold, PPTh).

  3. slope of the hypercapnic ventilatory response; [ Time Frame: Time 0, 60, 120, 180, 240, 300, 360 and 420 minutes after oxycodon or placebo administration. ]
    Slope

  4. plasma concentrations of THC, 11-OH-THC and oxycodone; a secondary analysis will be performed on the pharmacokinetic and pharmacodynamic data (PKPD modeling). [ Time Frame: Time 0, 30, 60, 95, 110, 130, 150, 210, 270, 275, 290, 310, 330, 390 and 450 minutes after oxycodon or placebo administration. ]
    Plasma concentration

  5. Bond & Lader questionnaire score [ Time Frame: Time 0, 30, 90, 150, 210, 270, 330, 390 and 450 minutes after oxycodon or placebo administration. ]
    The Bond and Lader scales are calculated from sixteen 100 mm visual analog scales.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05235503


Contacts
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Contact: Cornelis Jan CJ van Dam, MSc +31715299797 c.j.van_dam@lumc.nl
Contact: Monique van Velzen, Phd +31715262301 m.van_velzen@lumc.nl

Locations
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Netherlands
Leiden University Medical Center Recruiting
Leiden, Zuid Holland, Netherlands, 2333 ZA
Contact: Cornelis Jan CJ van Dam, MSc    31(0)715299797    c.j.van_dam@lumc.nl   
Contact: Monique van Velzen, Phd    +31(0)715262301    m.van_velzen@lumc.nl   
Sponsors and Collaborators
Leiden University Medical Center
Investigators
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Principal Investigator: Monique van Velzen, Phd LUMC
  Study Documents (Full-Text)

Documents provided by Albert Dahan, Leiden University Medical Center:
Informed Consent Form  [PDF] June 30, 2021

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Responsible Party: Albert Dahan, Coordinating investigator, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT05235503    
Other Study ID Numbers: P21.030
2021-000083-29 ( EudraCT Number )
NL76443.058.21 ( Other Identifier: CCMO Netherlands )
First Posted: February 11, 2022    Key Record Dates
Last Update Posted: February 11, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Insufficiency
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Respiration Disorders
Respiratory Tract Diseases