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Cannabis Effects on Electroencephalography (CEG)

Primary Purpose

Healthy Volunteers

Status

Terminated

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

Cannabis Sativa

Cannabis placebo

About this trial

This is an interventional other trial for Healthy Volunteers focused on measuring Cannabis, Recreational drugs, Neural oscillations, THC

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy male or female subjects.
Negative urine pregnancy test and effective contraception method for female of child-bearing potential (see footnote at the end of subheading 5).
Age ≥ 18 and ≤ 55 years.
Weight ≥ 50 kg and ≤ 100 kg.
Body mass index (BMI) ≥ 18 and ≤ 30.
Recreational cannabis use with a cannabis use history ≥ 6 months and a cannabis consumption in the last month ≥ 1 day/month and ≤ 2 days/week.
Last cannabis consumption ≥ 1 week before Day 1.
Negative urine drug test but for cannabis.
Consistent drug hair test (performed during screening) with drug use medical history.
Able to read Spanish and adhere to study requirements.
Not under any administrative or legal supervision.
Signed informed consent prior to any study-mandated procedure.

Exclusion Criteria:

Pregnant or nursing female.
Cannabis-naive subjects.
Life-time cannabis use disorder (CUD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM).
Recreational use of opioids, cocaine, psychostimulants within the last month.
Life-time other substance use disorders (SUD) according to the DSM-5 criteria using PRISM, except for mild alcohol use disorder and/or mild or moderate nicotine use disorder.
Life-time history of bipolar disorders, psychosis or suicidal attempts assessed by the Dual Diagnosis Screening Instrument (DDSI).
Past-12 months history of anxiety or depression assessed by the DDSI.
Life-time clinically significant cardiovascular, renal, pulmonary, hepatic, onco-hematological, endocrine, gastrointestinal or neurological disease.
Any other diseases or conditions that in the judgment of the investigator would interfere with the subject's ability to comply with study procedures or requirements and/or study results interpretation.
Any clinically significant findings in physical examination including vital signs, EEG and safety laboratory parameters.
Any prescription or over the counter drug (except occasional use of paracetamol) in the last 2 weeks before Day 1 of each period.
Patient included in a clinical study in the last three months.

Sites / Locations

IMIM (Hospital del Mar Medical Research Institute)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cannabis (B)

Cannabis placebo (B)

Arm Description

Subjects will be admitted in the center to receive 4 doses of inhaled cannabis in 3 days. Vital signs, blood test and electroencephalogram (Starlab® helmet) will be performed before and after every cannabis administration. Cannabis subjective effects will be assessed and a psychiatric research interview will also be performed at different times after administration.

Subjects will be admitted in the center to receive 4 doses of an inhaled treatment based on placebo-THC in 3 days. Vital signs, blood test and electroencephalogram (Starlab® helmet) will be performed before and after every administration. Cannabis subjective effects will be assessed and a psychiatric research interview will also be performed at different times after administration.

Outcomes

Primary Outcome Measures

Number of Participants with EEG alterations

THC induced EEG alterations, such as: Decrease in phase synchronization (intertrial coherence) of the 40 Hertz gamma band assessed by the auditory steady state response (ASSR). Decrease in evoked power of the 40 Hertz gamma band assessed by the auditory steady state response (ASSR). Decrease in P300 wave amplitude assessed by a three-stimulus auditory oddball task. Decrease in power of neural oscillations in resting state eyes-closed EEG. Increase in EEG complexity, measured by the Lempel-Ziv complexity. Decrease in EEG brain connectivity (band coherence, synchronicity likelihood) in resting state eyes-closed/open. Decrease in cross-frequency theta-gamma coupling.

Secondary Outcome Measures

Number of Participants with subjective effects

THC induced alterations in subjective and psychotomimetic effects, measured as increase in cannabis subjective effects and increase in psychopathology scale Psychotomimetic State Inventory (PSI) score.

Number of Participants with alterations in cardiovascular function

THC induced alterations in cardiovascular function, such as increased heart rate measured by a wearable medical device.

Number of Participants with neuroendocrine alterations

THC induced neuroendocrine alterations, such as increased cortisol plasma concentrations.

Time-profile of THC

Changes in concentration of THC in blood

Time-profile of OH-THC

Changes in concentration of OH-THC in blood

Time-profile of THC-COOH

Changes in concentration of THC-COOH in blood

Full Information

NCT ID

NCT04316598

First Posted

March 18, 2020

Last Updated

July 29, 2020

Sponsor

Parc de Salut Mar

1. Study Identification

Unique Protocol Identification Number

NCT04316598

Brief Title

Cannabis Effects on Electroencephalography

Acronym

CEG

Official Title

Monocenter, Double-Blind, Randomized, Placebo-Controlled, Parallel Group Study to Assess the Pharmacodynamic Effects of Cannabis on Neural Oscillations in Healthy Recreational Cannabis Users

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Terminated

Why Stopped

Terminated by the sponsor in the context of COVID-19 pandemia

Study Start Date

March 3, 2020 (Actual)

Primary Completion Date

July 9, 2020 (Actual)

Study Completion Date

July 9, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Parc de Salut Mar

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Background: Tetrahydrocannabinol (THC) is a partial CB1/CB2 agonist and causes its pharmacological effects by binding to cannabinoid receptors. CB1 receptors are predominantly located in the brain (highest densities at hippocampus, cerebellum and the striatum) and at low levels in the brainstem. CB2 receptors are predominantly in the spleen and in hematopoietic cells. THC is highly lipophilic and is readily absorbed and distributed to the brain and other organs. Most of the neuropsychological studies carried out so far show that the mainly affected neurocognitive functions in cannabis users are: memory, attention, psychomotor capacity, speed of information processing and alterations of executive functions (resistance to interference, planning capacity, decision-making, verbal fluency and working memory). These effects are dose-dependent. Hypothesis: Functional CB1 receptor activation by the THC contained in the cannabis flos will induce dose-dependent effects on EEG, physiological functions and behavior: EEG alterations. Increase in cannabis subjective effects. Increase in heart rate. Increase in psychopathology scale Psychotomimetic State Inventory (PSI) score. Increase in plasma cortisol concentrations. Objectives: Main pharmacodynamic objective: To assess the effects of Cannabis flos on electroencephalography (EEG) in healthy recreational cannabis users. Secondary pharmacodynamic objectives: (i) To assess the effects of Cannabis flos on: cannabis subjective effects, heart rate and psychopathology scale; (ii) To establish the pharmacokinetic/pharmacodynamic relationships between THC plasma concentrations and pharmacodynamic endpoints. Safety and tolerability objectives: To assess the safety and tolerability of THC in these subjects. Methods: Phase I, prospective, monocentric, double-blind, randomized, placebo-controlled, parallel group study to assess the THC effects on EEG neural oscillations in 16 healthy subjects with recreational cannabis use.

Detailed Description

Subjects will be randomly assigned in a 2:1 ratio to either Arm A (Cannabis) or Arm B (Cannabis placebo). The subjects, Investigators and designees involved in the conduct of the study will be blinded to the identity of the treatment administered during the study. In the active group (Arm A) subjects will be administered four single doses of 20 mg THC over 3 days, equivalent to 285.7 μg/kg. This dose is considered to be sufficient for eliciting the psychoactive effects of THC (> 5 ng/mL in plasma) and modify EEG, avoiding subjects to be too much behaviorally impaired. THC will be administered in the form of medical cannabis (Bedrocan®) inhaled by intrapulmonary route. It is featured in flos form (Cannabis sativa dried female flower) containing THC 22% and cannabidiol (CBD) <1%. A vaporization system (Mighty® Medic device) will be used for cannabis administration. Through this system, the final inhalation of THC is comparable to that of smoking cannabis while reducing the inhalation of toxic and irritating substances generated in the combustion of herbs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy Volunteers

Keywords

Cannabis, Recreational drugs, Neural oscillations, THC

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

Prospective, monocentric, double-blind, randomized, placebo-controlled, parallel group study. Subjects will be randomly assigned in a 2:1 ratio to study arms.

Masking

ParticipantCare ProviderInvestigator

Masking Description

The subjects, Investigators and designees involved in the conduct of the study will be blinded to the identity of the treatment administered during the study. The following precautions will be taken to ensure the integrity of the study blinding during the trial: The monodose capsules containing the treatment conditions will be prepared by an unblinded technician who will not be involved in any study assessment. The unblinded technician will also maintain records for drug accountability. Treatment will not be unblinded for an individual subject except for a medical emergency.

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cannabis (B)

Arm Type

Experimental

Arm Description

Arm Title

Cannabis placebo (B)

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cannabis Sativa

Other Intervention Name(s)

THC, Bedrocan®

Intervention Description

Subjects will receive a total of 4 inhaled doses of 20 mg of tetrahydrocannabinol (THC) in 3 days. Cannabis is provided as a medical grade cannabis flos (Cannabis sativa dried female flower) containing THC 22% and cannabidiol <1%, supplied by Bedrocan®. To avoid the respiratory disadvantages of smoking, a vaporization device (Mighty® Medic) will be used to inhale the drug. The prepared capsules will contain 90 mg of Cannabis flos, equivalent to 20 mg of THC.

Intervention Type

Drug

Intervention Name(s)

Cannabis placebo

Other Intervention Name(s)

Knaster

Intervention Description

Subjects will receive a total of 4 inhaled doses of cannabis placebo (THC <0,2%) in 3 days. Placebo cannabis is provided as a medical grade cannabis flos (Cannabis sativa dried female flower) containing cannabinoids <0.2%. To avoid the respiratory disadvantages of smoking, a vaporization device (Mighty® Medic) will be used to inhale the drug. The prepared capsules will contain 90 mg of cannabis placebo.

Primary Outcome Measure Information:

Title

Number of Participants with EEG alterations

Description

Time Frame

45 minutes pre-administration to 45 minutes post-administration

Secondary Outcome Measure Information:

Title

Number of Participants with subjective effects

Description

Time Frame

Before administration, at 15, 50, 75 and 105 minutes post-administration

Title

Number of Participants with alterations in cardiovascular function

Description

THC induced alterations in cardiovascular function, such as increased heart rate measured by a wearable medical device.

Time Frame

Before administration to 60 minutes post-administration

Title

Number of Participants with neuroendocrine alterations

Description

THC induced neuroendocrine alterations, such as increased cortisol plasma concentrations.

Time Frame

Before administration, at 10 and 60 minutes post-administration

Title

Time-profile of THC

Description

Changes in concentration of THC in blood

Time Frame

Before administration, at 10 and 60 minutes post-administration

Title

Time-profile of OH-THC

Description

Changes in concentration of OH-THC in blood

Time Frame

Before administration, at 10 and 60 minutes post-administration

Title

Time-profile of THC-COOH

Description

Changes in concentration of THC-COOH in blood

Time Frame

Before administration, at 10 and 60 minutes post-administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy male or female subjects. Negative urine pregnancy test and effective contraception method for female of child-bearing potential (see footnote at the end of subheading 5). Age ≥ 18 and ≤ 55 years. Weight ≥ 50 kg and ≤ 100 kg. Body mass index (BMI) ≥ 18 and ≤ 30. Recreational cannabis use with a cannabis use history ≥ 6 months and a cannabis consumption in the last month ≥ 1 day/month and ≤ 2 days/week. Last cannabis consumption ≥ 1 week before Day 1. Negative urine drug test but for cannabis. Consistent drug hair test (performed during screening) with drug use medical history. Able to read Spanish and adhere to study requirements. Not under any administrative or legal supervision. Signed informed consent prior to any study-mandated procedure. Exclusion Criteria: Pregnant or nursing female. Cannabis-naive subjects. Life-time cannabis use disorder (CUD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). Recreational use of opioids, cocaine, psychostimulants within the last month. Life-time other substance use disorders (SUD) according to the DSM-5 criteria using PRISM, except for mild alcohol use disorder and/or mild or moderate nicotine use disorder. Life-time history of bipolar disorders, psychosis or suicidal attempts assessed by the Dual Diagnosis Screening Instrument (DDSI). Past-12 months history of anxiety or depression assessed by the DDSI. Life-time clinically significant cardiovascular, renal, pulmonary, hepatic, onco-hematological, endocrine, gastrointestinal or neurological disease. Any other diseases or conditions that in the judgment of the investigator would interfere with the subject's ability to comply with study procedures or requirements and/or study results interpretation. Any clinically significant findings in physical examination including vital signs, EEG and safety laboratory parameters. Any prescription or over the counter drug (except occasional use of paracetamol) in the last 2 weeks before Day 1 of each period. Patient included in a clinical study in the last three months.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rafael de la Torre Fornell, Dr

Organizational Affiliation

IMIM (Hospital del Mar Medical Research Institute)

Official's Role

Principal Investigator

Facility Information:

Facility Name

IMIM (Hospital del Mar Medical Research Institute)

City

Barcelona

ZIP/Postal Code

08003

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

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