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Modulation of THC Effects by CBD: a Dose-ranging Study (SPECTRE)

Primary Purpose

Cannabis, THC

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
∆9-tetrahydrocannabinol
Sponsored by
Centre hospitalier de l'Université de Montréal (CHUM)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Cannabis

Eligibility Criteria

21 Years - 49 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Between 21 and 49 years of age, inclusively; Have used cannabis at least once in their lifetime and have used cannabis three days or less in the 30 days prior to enrollment; Be able to provide a signed informed consent; Willing to comply with study procedures and requirements as per protocol; Have a forced expiratory volume in first second (FEV) less than or equal to 90 %; Able to communicate and understand English or French language; For female participants: a. No childbearing potential, defined as: i. postmenopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age); or ii. Documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or b. For female of childbearing potential: i. Must have negative pregnancy test result at screening and at subsequent visits. ii. AND have no pregnancy plan while on the study iii. AND must agree to use a medically accepted method of birth control throughout the study. Exclusion criteria Participants will be excluded if any of the following criteria are met: Any disabling medical condition, as assessed by medical history, physical exam, vital signs and/or laboratory assessments that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent; Severe psychiatric condition (history of schizophrenia, schizoaffective disorder or bipolar disorder; current acute psychosis, mania or current suicidality based on the Mini International Neuropsychiatric Interview); Any other disabling, unstable or acute mental condition that, in the opinion of the study physician, precludes safe participation in the study or ability to provide fully informed consent; Known chronic liver disease or aspartate transaminase/alanine transaminase (AST/ALT) two times higher than upper limit of normal values at screening visit; Blood pressure higher than 130/80 mmHg; Kidney disorders; Bleeding disorders; Current moderate or severe DSM-5 substance use disorder (except nicotine) according to SCID-V; Currently pregnant, breastfeeding or planning to become pregnant either at screening or while enrolled in the study; Pending legal action or other reason that, in the opinion of the study physician, might prevent study completion; Use of medication within 7 days of experimental sessions; which, in the opinion of the Investigator, may interact with cannabis. Participation in clinical studies or undergoing other investigational procedure involving cannabis or cannabinoids administration within 30 days prior to randomization. Resting heart rate over 100 beats per minute. Current body mass index (BMI) over 29.9 kg/m2. Any clinically significant electrocardiogram abnormalities at screening visit.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    CBD:THC Group 1

    CBD:THC Group 2

    CBD:THC Group 3

    CBD:THC Group 4

    CBD:THC Group 5

    Arm Description

    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.

    Outcomes

    Primary Outcome Measures

    Objective and subjective measures of cannabinoids effect
    Based on the scores obtained on the observer items (objective) and the participant-rated items (subjective) from the Clinician Administered Dissociative State Scale (CADSS). The CADSS is a 28-item validated instrument, includes 5 observer items and 23 participant self-report items rated on a 5-point scale, ranging from 0 (not at all) to 4 (extremely) on eight items. The score will reflect the extent to which participants were observed to be under the effect of cannabinoids, i.e., in adissociative state.

    Secondary Outcome Measures

    Positive and Negative Affect
    Will be measured by the Positive and Negative Affect Schedule (PANAS). The PANAS is a 20-item validated questionnaire, used in both non-clinical and clinical populations.
    Neural oscillations
    Auditory oscillations, using an electroencephalogram (EEG), will be probe in response to 40-Hz FM and ascending/descending AM stimuli, using a 16-channel system with 250-Hz sampling rate and 24-bit resolution (model g.Nautilus PRO 16 g.SAHARA, g.tec, Schiedlberg, Austria).
    Anxiety Symptoms
    Symptoms of anxiety will be assessed using the States-Trait-Anxiety-Inventory (STAI). It consists of two 20-item self-report scales (trait and state anxiety) that measure the severity of anxiety in adults. Both subscales are composed of 20 statements rated on a 4-point Likert scale ranging from 1 ("not at all" and "almost never" for the state and trait subscales, respectively) to 4 ("very much" and "almost always" for the state and trait subscales, respectively).
    Subjective Drug Effects
    Drug Effect Questionnaire (twenty-three-item) will be use to assess participant's physical signs, symptoms associated with cannabis inhalation and desire to use the product. The Drug Effects Questionnaire uses visual analogue scale, ranging from 0 (not at all) to 100 (extremely).
    Experience with Study Products
    Subjective effects of cannabis will be assessed using the Cannabis Experience Questionnaire (CEQ), The CEQ measures participants' subjective experiences with cannabis consumption and consists of two subscales: pleasurable experiences (18 items), psychosis-like experiences (25 items), and after-effect experiences measuring the consequences of cannabis after use (12 items). Each item of each subscale is rated on a 5-point Likert scale, ranging from 1 (not at all) to 5 (extremely).
    Social Exposition Challenge
    This will help determine if different doses of CBD can modulate the feeling of paranoia and/or anxiety triggered by social interactions, in comparison to the control product. The research staff will give to the participant five dollars in cash. The participant will then be escorted out of the research center by a member of the research staff for a 10-minute walk to the hospital pharmacy with the instruction of purchasing an item of their choosing with the money. Once the task is completed, the participant will be escorted back to the research center. The research staff will walk approximately two meters behind the participant during the whole procedure and will be instructed not to engage in any conversation, unless the participant needs assistance or feels abnormally anxious.
    Change on cognition
    The Cambridge Neuropsychological Test Automated Battery tests will be used for the rapid assessment of multiple cognitive components.
    Success of Blinding Questionnaire
    To assess the success of the blind iwith the Blinding Success Questionnaire (BSQ). The specific aims of testing the blind are to a) determine which research product participants think they received and b) examine the associations between the research product participants think they received and their expectations, subjective cannabis perceptions, treatment outcomes, and side effects.
    Inhalation Adherence
    When the participant inhales the investigational product, research staff will fill a questionnaire assessing participant compliance.
    Change in Safety
    Adverse events will be collected prior to administration of the study product (T0) and following administration of the study product (T1, T2 and T3).
    Visit Intoxication Assessment
    Signs of intoxication will be assess using the modified Standardized Field Sobriety Test.

    Full Information

    First Posted
    September 29, 2023
    Last Updated
    October 23, 2023
    Sponsor
    Centre hospitalier de l'Université de Montréal (CHUM)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06099379
    Brief Title
    Modulation of THC Effects by CBD: a Dose-ranging Study
    Acronym
    SPECTRE
    Official Title
    Modulation of ∆9-tetrahydrocannabinol Acute Psychoactive Effects by Ranging Doses of Cannabidiol in Healthy, Occasional Cannabis Users: a Controlled, Triple Blind, Randomized, Cross-over Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 15, 2023 (Anticipated)
    Primary Completion Date
    July 31, 2025 (Anticipated)
    Study Completion Date
    December 31, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Centre hospitalier de l'Université de Montréal (CHUM)

    4. Oversight

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

    5. Study Description

    Brief Summary
    The purposes of this study are 1) to determine if CBD modulates THC-induced acute psychoactive effects at different CBD:THC ratios, compared with the control product (0:20, 20:20, 40:20, 80:20, 120:20) and 2) to determine if different doses of CBD modulate other THC induced behavioral effects, compared with the control product and 3)To explore qualitatively whether CBD modulates THC effects by mechanisms that are not detected with standard clinical research tools.
    Detailed Description
    Despite more than 40 years of research on the active compounds present in the cannabis plant, the influence of CBD consumption on the metabolism, pharmacology, and behavioral effects of THC remains fragmentary and scarcely documented in vivo in humans. Cannabis users are currently encouraged to choose products containing CBD, but evidence is lacking regarding its potential benefits when consumed jointly with THC across different ratios. Given the recent cannabis legalization in Canada and the widespread use of inhalation as the preferred mode of administration for non-therapeutic cannabis, closing this knowledge gap will help ensure public safety and allow regulatory bodies and public health authorities to elaborate more refined cannabis use guidelines and harm reduction strategies. It will also empower people who use cannabis to make more informed purchasing decisions and will drive the incubation of future research endeavors in the fields of medical and social sciences. The aim of this study is to improve our understanding of the (acute) behavioral and pharmacological effects of different doses of CBD administered concomitantly with THC via inhalation in individuals who engage in occasional cannabis use, taking into consideration multiple factors that can modulate such effects. This study will put to the test conceptions surrounding the interaction between specific cannabinoids by evaluating the role of CBD on the modulation of THC's effects pertaining to cognition, behavior, subjective experience, and physiological parameters.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Crossover Assignment
    Model Description
    In this crossover design, participants will be administered all phytocannabinoid doses contained in the four CBD:THC products and the control product (THC only) during participation in the study. Participant will be randomly assigned to one of the predetermined sequences with a CBD:THC product or control product at 5 dosages (CBD:THC of 0:20 mg, 20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg). Participants will be randomized based on a balanced 5 by 5 Latin square.
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    CBD:THC Group 1
    Arm Type
    Experimental
    Arm Description
    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.
    Arm Title
    CBD:THC Group 2
    Arm Type
    Experimental
    Arm Description
    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.
    Arm Title
    CBD:THC Group 3
    Arm Type
    Experimental
    Arm Description
    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.
    Arm Title
    CBD:THC Group 4
    Arm Type
    Experimental
    Arm Description
    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.
    Arm Title
    CBD:THC Group 5
    Arm Type
    Experimental
    Arm Description
    Group will receive four doses of CBD:THC ratio (20:20 mg, 40:20 mg, 80:20 mg and 120:20 mg) and a control product CBD:THC ratio (0:20 mg). Group will attend a total of five study visits (one for each study product) with at least 1 week between each visit. The order in which the study products will be administered depend on the randomization sequence.
    Intervention Type
    Drug
    Intervention Name(s)
    ∆9-tetrahydrocannabinol
    Other Intervention Name(s)
    Cannabidiol
    Intervention Description
    Phytocannabinoids from plant inflorescences (CBD and THC dominant) - inhaled
    Primary Outcome Measure Information:
    Title
    Objective and subjective measures of cannabinoids effect
    Description
    Based on the scores obtained on the observer items (objective) and the participant-rated items (subjective) from the Clinician Administered Dissociative State Scale (CADSS). The CADSS is a 28-item validated instrument, includes 5 observer items and 23 participant self-report items rated on a 5-point scale, ranging from 0 (not at all) to 4 (extremely) on eight items. The score will reflect the extent to which participants were observed to be under the effect of cannabinoids, i.e., in adissociative state.
    Time Frame
    Prior to the Product administration ,10 minutes and 60 minutes after inhalation
    Secondary Outcome Measure Information:
    Title
    Positive and Negative Affect
    Description
    Will be measured by the Positive and Negative Affect Schedule (PANAS). The PANAS is a 20-item validated questionnaire, used in both non-clinical and clinical populations.
    Time Frame
    Prior to the Product administration , 10 minutes and 60 minutes post inhalation
    Title
    Neural oscillations
    Description
    Auditory oscillations, using an electroencephalogram (EEG), will be probe in response to 40-Hz FM and ascending/descending AM stimuli, using a 16-channel system with 250-Hz sampling rate and 24-bit resolution (model g.Nautilus PRO 16 g.SAHARA, g.tec, Schiedlberg, Austria).
    Time Frame
    Prior to the Product administration, 50 minutes post inhalation and at the end of the study visit, approximatively 120 minutes after inhalation
    Title
    Anxiety Symptoms
    Description
    Symptoms of anxiety will be assessed using the States-Trait-Anxiety-Inventory (STAI). It consists of two 20-item self-report scales (trait and state anxiety) that measure the severity of anxiety in adults. Both subscales are composed of 20 statements rated on a 4-point Likert scale ranging from 1 ("not at all" and "almost never" for the state and trait subscales, respectively) to 4 ("very much" and "almost always" for the state and trait subscales, respectively).
    Time Frame
    Prior to the Product administration, 10 minutes and 60 minutes after inhalation
    Title
    Subjective Drug Effects
    Description
    Drug Effect Questionnaire (twenty-three-item) will be use to assess participant's physical signs, symptoms associated with cannabis inhalation and desire to use the product. The Drug Effects Questionnaire uses visual analogue scale, ranging from 0 (not at all) to 100 (extremely).
    Time Frame
    10 minutes and 60 minutes after inhalation
    Title
    Experience with Study Products
    Description
    Subjective effects of cannabis will be assessed using the Cannabis Experience Questionnaire (CEQ), The CEQ measures participants' subjective experiences with cannabis consumption and consists of two subscales: pleasurable experiences (18 items), psychosis-like experiences (25 items), and after-effect experiences measuring the consequences of cannabis after use (12 items). Each item of each subscale is rated on a 5-point Likert scale, ranging from 1 (not at all) to 5 (extremely).
    Time Frame
    120 minutes after inhalation
    Title
    Social Exposition Challenge
    Description
    This will help determine if different doses of CBD can modulate the feeling of paranoia and/or anxiety triggered by social interactions, in comparison to the control product. The research staff will give to the participant five dollars in cash. The participant will then be escorted out of the research center by a member of the research staff for a 10-minute walk to the hospital pharmacy with the instruction of purchasing an item of their choosing with the money. Once the task is completed, the participant will be escorted back to the research center. The research staff will walk approximately two meters behind the participant during the whole procedure and will be instructed not to engage in any conversation, unless the participant needs assistance or feels abnormally anxious.
    Time Frame
    50 minutes after inhalation
    Title
    Change on cognition
    Description
    The Cambridge Neuropsychological Test Automated Battery tests will be used for the rapid assessment of multiple cognitive components.
    Time Frame
    Prior to the Product administration (only at Visite 1) and 10 minutes after inhalation at each visit
    Title
    Success of Blinding Questionnaire
    Description
    To assess the success of the blind iwith the Blinding Success Questionnaire (BSQ). The specific aims of testing the blind are to a) determine which research product participants think they received and b) examine the associations between the research product participants think they received and their expectations, subjective cannabis perceptions, treatment outcomes, and side effects.
    Time Frame
    10 minutes and 120 minutes after inhalation
    Title
    Inhalation Adherence
    Description
    When the participant inhales the investigational product, research staff will fill a questionnaire assessing participant compliance.
    Time Frame
    During inhalation procedure
    Title
    Change in Safety
    Description
    Adverse events will be collected prior to administration of the study product (T0) and following administration of the study product (T1, T2 and T3).
    Time Frame
    Baseline,10 minutes, 60 minutes and 120 minutes after inhalation
    Title
    Visit Intoxication Assessment
    Description
    Signs of intoxication will be assess using the modified Standardized Field Sobriety Test.
    Time Frame
    Through study visit completion, approximatively 120 minutes after product inhalation
    Other Pre-specified Outcome Measures:
    Title
    Change in plasma concentrations of CBD
    Description
    Plasma levels of CBD will be determined by high performance liquid chromatography-tandem mass spectrometry.
    Time Frame
    Prior to the Product administration and 5,15, 60, 90, and 120 minutes after administration
    Title
    Change in plasma concentrations of THC
    Description
    Plasma levels of THC will be determined by high performance liquid chromatography-tandem mass spectrometry.
    Time Frame
    Prior to the Product administration and 5,15, 60, 90, and 120 minutes after administration
    Title
    Change in plasma concentrations of Anandamide (AEA)
    Description
    Plasma levels of CBD and THC will be determined by high performance liquid chromatography-tandem mass spectrometry.
    Time Frame
    Prior to the Product administration and 5,15, 60, 90, and 120 minutes after administration
    Title
    Change in plasma concentrations of 2-Arachidonoylglycerol (2-AG)
    Description
    Plasma levels of CBD and THC will be determined by high performance liquid chromatography-tandem mass spectrometry.
    Time Frame
    Prior to the Product administration and 5,15, 60, 90, and 120 minutes after administration
    Title
    Genetic markers
    Description
    To explore potential genetic factors that could explain at least in part some of the participants' responses to the study outcomes and that have been associated with specific candidate genes (e.g., COMT, AKT1, DRD2, FAAH and cytochrome P450 genes). Using buccal swabs from EndoDNA test kits. These DNA tests will be used to map known genetic variants associated with the endocannabinoidome and related physiological systems to identify specific genotypes that correlate with neurocognitive and behavioral effects measured for each study product for an example application of the method).
    Time Frame
    Baseline, Prior to the Product administration (only at visite 1)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    21 Years
    Maximum Age & Unit of Time
    49 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Between 21 and 49 years of age, inclusively; Have used cannabis at least once in their lifetime and have used cannabis three days or less in the 30 days prior to enrollment; Be able to provide a signed informed consent; Willing to comply with study procedures and requirements as per protocol; Have a forced expiratory volume in first second (FEV) less than or equal to 90 %; Able to communicate and understand English or French language; For female participants: a. No childbearing potential, defined as: i. postmenopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age); or ii. Documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or b. For female of childbearing potential: i. Must have negative pregnancy test result at screening and at subsequent visits. ii. AND have no pregnancy plan while on the study iii. AND must agree to use a medically accepted method of birth control throughout the study. Exclusion criteria Participants will be excluded if any of the following criteria are met: Any disabling medical condition, as assessed by medical history, physical exam, vital signs and/or laboratory assessments that, in the opinion of the study physician, precludes safe participation in the study or the ability to provide fully informed consent; Severe psychiatric condition (history of schizophrenia, schizoaffective disorder or bipolar disorder; current acute psychosis, mania or current suicidality based on the Mini International Neuropsychiatric Interview); Any other disabling, unstable or acute mental condition that, in the opinion of the study physician, precludes safe participation in the study or ability to provide fully informed consent; Known chronic liver disease or aspartate transaminase/alanine transaminase (AST/ALT) two times higher than upper limit of normal values at screening visit; Blood pressure higher than 130/80 mmHg; Kidney disorders; Bleeding disorders; Current moderate or severe DSM-5 substance use disorder (except nicotine) according to SCID-V; Currently pregnant, breastfeeding or planning to become pregnant either at screening or while enrolled in the study; Pending legal action or other reason that, in the opinion of the study physician, might prevent study completion; Use of medication within 7 days of experimental sessions; which, in the opinion of the Investigator, may interact with cannabis. Participation in clinical studies or undergoing other investigational procedure involving cannabis or cannabinoids administration within 30 days prior to randomization. Resting heart rate over 100 beats per minute. Current body mass index (BMI) over 29.9 kg/m2. Any clinically significant electrocardiogram abnormalities at screening visit.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pamela Lachance, PhD
    Phone
    514-890-8000
    Ext
    30938
    Email
    pamela.lachance-touchette.chum@ssss.gouv.qc.ca
    First Name & Middle Initial & Last Name or Official Title & Degree
    François-Olivier Hébert, PhD
    Phone
    581 741-4941
    Email
    francois-olivier.hebert.chum@ssss.gouv.qc.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Didier Jutras-Aswad, MD, MS
    Organizational Affiliation
    CRCHUM
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Modulation of THC Effects by CBD: a Dose-ranging Study

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