- To investigate whether olanzapine influences the (psychomimetic) effects of THC, in particular on the Positive and Negative Syndrome Scale (PANSS) - To further explore the pharmacologic basis of the THC model - To investigate the effects of…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- the PANSS (Positive and Negative Syndrome Scale - a widely used, clinical
questionnaire based on a semi-structured interview)
- Visual Analogue Scales (VAS - Bond & Lader, Bowdle - validated scales to
objectify subjective parameters)
Secondary outcome
- other parameters for the functioning of the central nervous systems (see
protocol chapter 7)
Background summary
Background of the study:
There is a large amount of evidence suggesting a relation between cannabis and
psychosis and the possible increase in dopamine in the prefrontal cortex by
THC. THC-induced psychomimetic effects could be used as a practical
'psychosis'-model to investigate the therapeutical effects of a (novel)
antipsychotic. The current study is designed to investigate the
'THC-psychosis-model' for the second time. The hypothesis is that olanzapine
will lead, in a similar manner as haloperidol (previous study), to less
'psychomimetic' effects in reaction to the THC-challenge.
Study objective
- To investigate whether olanzapine influences the (psychomimetic) effects of
THC, in particular on the Positive and Negative Syndrome Scale (PANSS)
- To further explore the pharmacologic basis of the THC model
- To investigate the effects of olanzapine on the central nervous system
- To further investigate the effects of THC on the central nervous system
- To investigate the genetic influence on THC sensitivity
Study design
Double-blind, randomised, placebo-controlled, 5-way cross-over interaction
study in healthy volunteers.
Intervention
The drugs used in the study are olanzapine 10 mg orally, diphenhydramine 2x15
mg orally and/or THC intrapulmonary (2, 4, and 6 mg with intervals of 90
minutes) or placebo of any of these drugs.
Study burden and risks
Screening: medical history taking, physical examination, venapuntion
(haematology, chemistry, virology), saliva sampling (determination of specified
haplotypes), drugs screening, personality questionnaires
5 occasions: repeated performance of several tests, insertion of intravenous
catheter for repeated blood sampling, ECG, three inhalations of THC (or
placebo).
Follow-up: physical examination, ECG
Restrictions: during the study period, restriction will be applied to living
pattern and the use of alcohol, tobacco, cafeine, recreational drugs and
medication.
Side-effects: all study drugs can lead to drowsiness, dizziness, nausea and a
light increase in heart rate. THC can cause a 'high' sensation and perceptions
may change. A rare side-effect of olanzapine are muscle spasms/stiffness, which
can be easily treated with biperiden.
Zernikedreef 10
2333 CL Leiden
Nederland
Zernikedreef 10
2333 CL Leiden
Nederland
Listed location countries
Age
Inclusion criteria
• Male sex
• Age between 18 and 45 (extremes included)
• Body Mass Index (BMI) between 18 and 30 kg/m2 (extremes included)
• Mild cannabis user for at least one year, defined as use of cannabis no more than once a week (as an average in the last year)
• Ability to refrain from using cannabinoids (other than the THC used in the study) from at least two weeks prior to the first treatment period till the end of the follow-up periods
• Willing to give written informed consent to participate in the study and to comply with the study procedures
Exclusion criteria
• Clinically significant (history of) psychiatric illness (including substance abuse)
• Clinically significant cardiac, pulmonary, gastrointestinal, hepatic, renal, haematological, endocrine or neurological disease as determined by medical history, physical examination, ECG or laboratory test results
• Family history (first-degree relatives) of relevant psychiatric disorders and/or family history (second-degree relatives) of psychotic disorders
• Participation in a clinical study within the past three months
• Participation in four or more clinical studies in the past twelve months
• Positive urine screen for recreational drugs, i.e. cocaine, opioids, benzodiazepines, amphetamines, metamphetamines, or MDMA. THC will be tested as well; since volunteers are cannabis users, subjects with a positive THC urine test will be tested again and have to be found THC-negative before the first study day. Subjects with a positive drug test on a study day, including THC, will be excluded
• Exposure to any medication, including over-the-counter medication and herbal agents, 14 days prior to randomization (except paracetamol)
• Exposure to prescription medication within 30 days prior to screening
• Positive testing for Hepatitis B or C, or HIV-1 or HIV-2
• Smokes more than four cigarettes per day
• Unable or unwilling to refrain from alcohol, starting 24 hours before each study day until the end of the study day
• Unable or unwilling to refrain from smoking on study days
• Unable or unwilling to refrain from xanthine (i.e. caffeine) intake on study days
• Unable or unwilling to refrain from quinine (bitter drinks in general, i.e. tonic, grapefruit juice) from 14 days before dosing until discharge
• Unable or unwilling to refrain from heavy physical exercise 24 hours before study days
• Unable or unwilling to maintain a regular day/night rhythm during the study
• Donation (or loss) of more blood, including this study, than allowed by the regulations of the Dutch blood bank (Sanquin)
• Relevant (history of) drug allergy or hypersensitivity to drugs
• Subject is the investigator or any sub-investigator, or a subordinate of the investigator or any sub-investigator
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-008520-33-NL |
| CCMO | NL26986.058.09 |