Cannabis Effects on Electroencephalography

NCT04316598 | Terminated Phase 1

• 1 other identifier: IMIMFTCL_CEG
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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:

1. 1.EEG alterations.
2. 2.Increase in cannabis subjective effects.
3. 3.Increase in heart rate.
4. 4.Increase in psychopathology scale Psychotomimetic State Inventory (PSI) score.
5. 5.Increase in plasma cortisol concentrations.

Conditions

Healthy Volunteers

Keywords

Cannabis; Recreational drugs; Neural oscillations; THC

Outcome Measures

Primary Outcomes (1)

• 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.

  45 minutes pre-administration to 45 minutes post-administration

Secondary Outcomes (6)

• Number of Participants with subjective effects

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

• Number of Participants with alterations in cardiovascular function

  Before administration to 60 minutes post-administration

• Number of Participants with neuroendocrine alterations

  Before administration, at 10 and 60 minutes post-administration

• Time-profile of THC

  Before administration, at 10 and 60 minutes post-administration

• Time-profile of OH-THC

  Before administration, at 10 and 60 minutes post-administration

Study Arms (2)

Cannabis (B)

EXPERIMENTAL

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.

Drug: Cannabis Sativa

Cannabis placebo (B)

PLACEBO COMPARATOR

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.

Drug: Cannabis placebo

Interventions

Cannabis Sativa DRUG

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.

Also known as: THC, Bedrocan®

Cannabis (B)

Cannabis placebo DRUG

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.

Also known as: Knaster

Cannabis placebo (B)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Parc de Salut Mar: lead

Study Sites (1)

IMIM (Hospital del Mar Medical Research Institute)

Barcelona, 08003, Spain

Location

MeSH Terms

Conditions

Marijuana Abuse

Interventions

nabiximols; Dronabinol

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Rafael de la Torre Fornell, Dr

  IMIM (Hospital del Mar Medical Research Institute)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: March 18, 2020
• First Posted: March 20, 2020
• Study Start: March 3, 2020
• Primary Completion: July 9, 2020
• Study Completion: July 9, 2020
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)