In this study we will measure the effect of Bedrocan which contains primarily *9-tetrahydrocannabinol (THC) and a minute quantity cannabidiol (CBD), on ventilation at 55 mmHg end-tidal PCO2 in 20 healthy volunteers and the combination of THC and 20…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
opiaat bijwerkingen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective: To measure the effect of inhaled THC (100 mg Bedrocan) on
ventilation at isohypercapnia (end-tidal PCO2 = 55 mmHg) without and with
concomitant intake of 20 mg oxycodone immediate release (IR) tablet in healthy
volunteers 90 min after oxycodone intake.
Secondary outcome
Secondary objective: To measure the effect of inhaled THC (100 mg Bedrocan)
without and with concomitant intake of 20 mg oxycodone immediate release (IR)
on
- occurrence of apneic events;
- occurrence of desaturation events;
- baseline ventilation;
- psychomimetic side effects as measured by Bowdle and Bond & Lader
questionnaires;
- cognition (p-deletion test)
- pain pressure threshold
- plasma concentrations of THC and oxycodone;
- blood pressure and heart rate.
Background summary
Opioids are commonly prescribed for moderate to severe pain. While initially
intended for acute and cancer pain, opioids are currently frequently considered
and prescribed in chronic noncancer pain. A consequence of this behavior is the
increase in opioid misuse and abuse. The rate of unintentional drug overdose is
rapidly increasing, not only in the Unites States but also in the Netherlands.
A potential lethal consequence of opioid overdose is opioid-induced respiratory
depression. Additionally, it is well known that opioids are often used (and
abused) in combination with other legal or illicit substances, for example
alcohol, benzodiazepines or cannabis, including medicinal (i.e. doctor
prescribed) cannabis. We previously showed that combining ethanol with
oxycodone (20 mg) increases respiratory depression, indicative of a dangerous
alcohol-opioid combination (van der Schrier et al. Anesthesiology 2017; 102:
115-122). There are no data on the interaction between oxycodone and cannabis
on the ventilatory control system. In our opinion, there is the false premise
that cannabis has no effect on breathing. Apart from a direct effect on
receptors in the brainstem, the sedative effects of cannabis may compromise
breathing. 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 furthering research on opioids, opioid-drug
interaction and alternatives for the treatment of various chronic illnesses and
chronic pain. Additionally, we expect that many patients at home using
oxycodone, also use (coffeeshop) cannabis.
Study objective
In this study we will measure the effect of Bedrocan which contains primarily
*9-tetrahydrocannabinol (THC) and a minute quantity cannabidiol (CBD), on
ventilation at 55 mmHg end-tidal PCO2 in 20 healthy volunteers and the
combination of THC and 20 mg oral oxycodone immediate release tablets. Primary
endpoint is the effect of inhaled THC on ventilation at end-tidal PCO2 = 55
mmHg without and with concomitant intake of 20 mg oxycodone immediate release
(IR) tablet in healthy volunteers 120 min after oxycodone intake. In this study
we will use the Volcano cannabis vaporizer to vaporize 100 mg Bedrocan into an
8 L balloon. Volunteers will inhale the cannabis vapor from the balloon.
Study design
The design of the study is randomized, placebo-controlled crossover. Each
subject will be studied twice, on occasion 1 he or she will receive THC and a
placebo opioid capsule, and on occasion 2 THC and an oxycodone capsule. The
visits to the lab will be randomized.
Intervention
inhalation Bedrocan (with THC) and intake oxycodone or placebo
On fixed timepoints:
- respiratory measurements by giving CO2
- experimental pain test
- questionnaires
- blood sampling
Study burden and risks
The burden/risks for the volunteers are the occurrence of side effects from
cannabis or oxycodone. Oxycodone may induce opioid-typical side effects such as
respiratory depression (research endpoint), nausea/vomiting and sedation, of
which nausea and vomiting is most burdensome. Other side effects, which are
also cannabis related, include drug high, euphoria/dysphoria,
dizziness/lightheadedness. During the study, we will closely monitor the
subjects and treat side effects, most importantly nausea by administration of
an antiemetic.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers of either sex with earlier experience with cannabis (>2
lifetime exposures and <2x/week in the last 12 months).
- 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 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.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-000083-29-NL |
| ClinicalTrials.gov | NCT05235503 |
| CCMO | NL76443.058.21 |