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Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids - a PET Study

Primary Purpose

Healthy Volunteers, Modeling Psychosis

Status
Unknown status
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Delta-9-tetrahydrocannabinol
Cannabidiol
Placebo
Sponsored by
Central Institute of Mental Health, Mannheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy Volunteers focused on measuring delta-9-tetrahydrocannabinol, cannabidiol, COMT

Eligibility Criteria

18 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Informed consent given by the subject
  • Healthy young man (age between 18 and 45) insightful to the study (WST> 95)
  • Right handedness
  • At least one time consumption of Cannabis but less than 10 times/ per lifetime, no consumption of other psychotropic agents (despite coffee or nicotine), no alcohol abuse
  • Negative drug-screening at the time of screening
  • Body Mass Index between 18 and 30

Exclusion Criteria:

  • Lack of accountability
  • Participation in other interventional trials
  • Severe medical or neurological illness, especially cardiovascular, renal, advanced respiratory, hematological or endocrinological failures or infectious diseases (acute hepatitis A, B or C or HIV) assessed at the time of the screening by the subject's history, clinical examination and laboratory testing, at the discretion of the investigator
  • Any known psychiatric illness in the participant's history
  • Known family history concerning psychiatric disorders
  • Cannabis consumption within the last six months
  • Consumption of any illegal drugs (except cannabis in history, see above)
  • Intake of interfering medication, at the discretion of the investigator
  • High intracranial pressure
  • Any disorders in stereoscopic vision (measured by the TNO-Test, Lamerics, Utrecht) or hearing deficits
  • Contraindications due to the Investigators Brochure Contraindication for Magnetic Resonance Imaging (e.g. cardiac pacemaker, claustrophobia, attached brace, in body metal, tattoos) or lumbar puncture (e.g. local or systemic infection, disturbance of blood coagulation, medication with anticoagulants like Phenprocoumon) or contradiction for the PET-CT method and the radiopharmaceutical

Sites / Locations

  • Central Institute of Mental Health

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

THC

CBD

CBD+THC

Placebo

Arm Description

Subjects receive 20 mg delta-9-tetrahydrocannabinol (2 capsules containing 10 mg each) and corresponding cannabidiol placebo capsules.

Subjects receive 800 mg cannabidiol (4 capsules containing 200 mg each) and corresponding delta-9-tetrahydrocannabinol placebo capsules.

Subjects receive 800 mg cannabidiol (4 capsules containing 200 mg each) and 20 mg delta-9-tetrahydrocannabinol (2 capsules containing 10 mg each)

Subjects receive corresponding delta-9-tetrahydrocannabinol and cannabidiol placebo capsules

Outcomes

Primary Outcome Measures

Change in Positive and Negative Syndrome Scale (total score, PANSS T) from baseline to post drug intake of both on induction of psychotic symptoms, endocannabinoid levels in human body fluids, neuronal processing, and D2-receptor availability

Secondary Outcome Measures

Change in PANSS subscores and clusters (baseline to post drug intake)
Change in Digit Symbol Coding
Change in Letter-Number-Sequencing
Change in emotional state (EWL, "Eigenschaftswörterliste")
Change in attentional state (d2-test of attention d2-R)
Change in imagination (Bett's Questionaire upon Mental Imagery)
Change in binocular depth inversion illusion (BDII)
Change in Wisconsin Card Sorting Test Performance
Assessment of hallucinogenic states scale (APZ) (post drug intake)
questionaire
Safety and tolerability assessments including (S)AEs, physical examination, vital signs (including heart rate and systolic and diastolic blood pressure in both supine and standing positions), and detailed laboratory assessments
Metabolic markers post drug intake (blood)
Metabolic markers post drug intake (cerebrospinal fluid)
D2-receptor availability post drug intake

Full Information

First Posted
July 3, 2015
Last Updated
August 12, 2019
Sponsor
Central Institute of Mental Health, Mannheim
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1. Study Identification

Unique Protocol Identification Number
NCT02492074
Brief Title
Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids - a PET Study
Official Title
Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids on the Endocannabinoid System and Brain Function
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 2020 (Anticipated)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
May 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Central Institute of Mental Health, Mannheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The study evaluates the gene-environment interaction of the COMT-genotype on the effects of the phytocannabinoids delta-9-tetrahydrocannabinol, cannabidiol or a combination of both on induction of psychotic symptoms, endocannabinoid levels in human body fluids, neuronal processing, and neural oscillations. In addition the effects of the phytocannabinoids on lipid levels in serum and cerebrospinal fluid, cognition, neuronal processing assessed by fMRI as well as D2-receptor availability assessed by [18F] desmethoxyfallypride.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers, Modeling Psychosis
Keywords
delta-9-tetrahydrocannabinol, cannabidiol, COMT

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
THC
Arm Type
Experimental
Arm Description
Subjects receive 20 mg delta-9-tetrahydrocannabinol (2 capsules containing 10 mg each) and corresponding cannabidiol placebo capsules.
Arm Title
CBD
Arm Type
Experimental
Arm Description
Subjects receive 800 mg cannabidiol (4 capsules containing 200 mg each) and corresponding delta-9-tetrahydrocannabinol placebo capsules.
Arm Title
CBD+THC
Arm Type
Experimental
Arm Description
Subjects receive 800 mg cannabidiol (4 capsules containing 200 mg each) and 20 mg delta-9-tetrahydrocannabinol (2 capsules containing 10 mg each)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects receive corresponding delta-9-tetrahydrocannabinol and cannabidiol placebo capsules
Intervention Type
Drug
Intervention Name(s)
Delta-9-tetrahydrocannabinol
Other Intervention Name(s)
Dronabinol
Intervention Description
oral administration of delta-9-tetrahydrocannabinol
Intervention Type
Drug
Intervention Name(s)
Cannabidiol
Intervention Description
oral administration of cannabidiol
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
oral administration of placebo
Primary Outcome Measure Information:
Title
Change in Positive and Negative Syndrome Scale (total score, PANSS T) from baseline to post drug intake of both on induction of psychotic symptoms, endocannabinoid levels in human body fluids, neuronal processing, and D2-receptor availability
Time Frame
up to 6 hours
Secondary Outcome Measure Information:
Title
Change in PANSS subscores and clusters (baseline to post drug intake)
Time Frame
up to 4 hours
Title
Change in Digit Symbol Coding
Time Frame
up to 6 hours
Title
Change in Letter-Number-Sequencing
Time Frame
up to 6 hours
Title
Change in emotional state (EWL, "Eigenschaftswörterliste")
Time Frame
up to 6 hours
Title
Change in attentional state (d2-test of attention d2-R)
Time Frame
up to 6 hours
Title
Change in imagination (Bett's Questionaire upon Mental Imagery)
Time Frame
up to 6 hours
Title
Change in binocular depth inversion illusion (BDII)
Time Frame
up to 6 hours
Title
Change in Wisconsin Card Sorting Test Performance
Time Frame
up to 6 hours
Title
Assessment of hallucinogenic states scale (APZ) (post drug intake)
Description
questionaire
Time Frame
1 day
Title
Safety and tolerability assessments including (S)AEs, physical examination, vital signs (including heart rate and systolic and diastolic blood pressure in both supine and standing positions), and detailed laboratory assessments
Time Frame
1 day
Title
Metabolic markers post drug intake (blood)
Time Frame
up to 4 hours
Title
Metabolic markers post drug intake (cerebrospinal fluid)
Time Frame
up to 4 hours
Title
D2-receptor availability post drug intake
Time Frame
up to 5 hours
Other Pre-specified Outcome Measures:
Title
Assessment of biomarker profiles in serum and cerebrospinal fluid of subjects
Description
Comparison of biomarker profiles in serum and cerebrospinal fluid after different treatments
Time Frame
1 day

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Informed consent given by the subject Healthy young man (age between 18 and 45) insightful to the study (WST> 95) Right handedness At least one time consumption of Cannabis but less than 10 times/ per lifetime, no consumption of other psychotropic agents (despite coffee or nicotine), no alcohol abuse Negative drug-screening at the time of screening Body Mass Index between 18 and 30 Exclusion Criteria: Lack of accountability Participation in other interventional trials Severe medical or neurological illness, especially cardiovascular, renal, advanced respiratory, hematological or endocrinological failures or infectious diseases (acute hepatitis A, B or C or HIV) assessed at the time of the screening by the subject's history, clinical examination and laboratory testing, at the discretion of the investigator Any known psychiatric illness in the participant's history Known family history concerning psychiatric disorders Cannabis consumption within the last six months Consumption of any illegal drugs (except cannabis in history, see above) Intake of interfering medication, at the discretion of the investigator High intracranial pressure Any disorders in stereoscopic vision (measured by the TNO-Test, Lamerics, Utrecht) or hearing deficits Contraindications due to the Investigators Brochure Contraindication for Magnetic Resonance Imaging (e.g. cardiac pacemaker, claustrophobia, attached brace, in body metal, tattoos) or lumbar puncture (e.g. local or systemic infection, disturbance of blood coagulation, medication with anticoagulants like Phenprocoumon) or contradiction for the PET-CT method and the radiopharmaceutical
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
F. Markus Leweke, MD
Phone
+49 621 1703 2321
Email
leweke@cimh.de
First Name & Middle Initial & Last Name or Official Title & Degree
Cathrin Rohleder, PhD
Phone
+49 621 1703 2333
Email
rohleder@cimh.de
Facility Information:
Facility Name
Central Institute of Mental Health
City
Mannheim
State/Province
BW
ZIP/Postal Code
68159
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
F. Markus Leweke, MD
Email
leweke@cimh.de

12. IPD Sharing Statement

Learn more about this trial

Gene-Environment-Interaction: Influence of the COMT Genotype on the Effects of Different Cannabinoids - a PET Study

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