Healthy VolunteersPhase 1CEGNCT04316598
Cannabis Effects on Electroencephalography
A Phase 1 study testing Cannabis Sativa in people with Healthy Volunteers, run by Parc de Salut Mar at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Cannabis Sativa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteSpain
- Study dates
- 3 Mar 2020to 9 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Healthy Volunteers
- Being tested
- Cannabis Sativa, Cannabis placebo
- Keywords
- Cannabis, Recreational drugs, Neural oscillations, THC
- Medical subject headings
- Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cannabis SativaDrug
Also called THC, Bedrocan®
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.
Cannabis placeboDrug
Also called Knaster
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cannabis placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 45 minutes pre-administration to 45 minutes post-administration
Secondary outcomes (6)
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.
Measured: Before administration, at 15, 50, 75 and 105 minutes post-administration
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.
Measured: Before administration to 60 minutes post-administration
Number of Participants with neuroendocrine alterations
THC induced neuroendocrine alterations, such as increased cortisol plasma concentrations.
Measured: Before administration, at 10 and 60 minutes post-administration
Time-profile of THC
Changes in concentration of THC in blood
Measured: Before administration, at 10 and 60 minutes post-administration
Time-profile of OH-THC
Changes in concentration of OH-THC in blood
Measured: Before administration, at 10 and 60 minutes post-administration
Time-profile of THC-COOH
Changes in concentration of THC-COOH in blood
Measured: Before administration, at 10 and 60 minutes post-administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start3 Mar 2020
- Primary completion9 Jul 2020
- Study completion9 Jul 2020
Why it stopped: Terminated by the sponsor in the context of COVID-19 pandemia
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rafael de la Torre Fornell, Dr, Principal investigator, IMIM (Hospital del Mar Medical Research Institute)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04316598
- Sponsor's protocol ID
- IMIMFTCL_CEG
- Acronym
- CEG
- Status last verified
- Jul 2020
- First submitted
- 18 Mar 2020
- Last updated
- 31 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04316598
- Acronym / sponsor ID
- CEG / IMIMFTCL_CEG
- Conditions
- Healthy Volunteers
- Keywords
- Cannabis, Recreational drugs, Neural oscillations, THC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated by the sponsor in the context of COVID-19 pandemia
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Study start
- 3 Mar 2020 (actual)
- Primary completion
- 9 Jul 2020 (actual)
- Study completion
- 9 Jul 2020 (actual)
- First posted
- 20 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Cannabis (B) | Experimental | Drug: Cannabis SativaSubjects 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. |
| Cannabis placebo (B) | Placebo comparator | Drug: Cannabis placeboSubjects 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cannabis SativaAlso: THC, Bedrocan®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. | Drug | Cannabis (B) |
| Cannabis placeboAlso: KnasterSubjects 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. | Drug | Cannabis placebo (B) |
Primary outcome
Number of Participants with EEG alterations
Time frame: 45 minutes pre-administration to 45 minutes post-administration
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.
6 secondary outcomes
Number of Participants with subjective effects
Time frame: Before administration, at 15, 50, 75 and 105 minutes post-administration
Number of Participants with alterations in cardiovascular function
Time frame: Before administration to 60 minutes post-administration
Number of Participants with neuroendocrine alterations
Time frame: Before administration, at 10 and 60 minutes post-administration
Time-profile of THC
Time frame: Before administration, at 10 and 60 minutes post-administration
Time-profile of OH-THC
Time frame: Before administration, at 10 and 60 minutes post-administration
Time-profile of THC-COOH
Time frame: Before administration, at 10 and 60 minutes post-administration
Results and safety
The study was stopped early (reason given: Terminated by the sponsor in the context of COVID-19 pandemia). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rafael de la Torre Fornell, Dr principal investigator
IMIM (Hospital del Mar Medical Research Institute)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cannabis Sativa in people with Healthy Volunteers, run by Parc de Salut Mar at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated by the sponsor in the context of COVID-19 pandemia). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with EEG alterations (time frame: 45 minutes pre-administration to 45 minutes post-administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020; AzTrials last refreshed its copy on 31 Oct 2026.