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Tetrahydrocannabinol (THC) and Sleep

Primary Purpose

Sleep, THC, Marijuana

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dronabinol
Sponsored by
Oregon Health and Science University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Sleep

Eligibility Criteria

21 Years - 34 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Frequent Cannabis Use (>3x/week for the prior 3 months) or
  • No Cannabis Use (Less than 10x ever)

Exclusion Criteria:

  • Sleep Apnea
  • Pregnancy
  • Diabetes
  • Cardiovascular disease
  • Chronic Pain
  • History of seizures
  • Severe Hepatic impairment
  • Conditions associated with clinically relevant cognitive impairment
  • Symptoms of acute or active illness (e.g., fever and leukocytosis)
  • Evidence of psychopathology on the Beck Depression Index II (BDI-II or in a structured clinical interview with a physician
  • History of severe psychiatric illnesses (including such as alcoholism, drug dependency including a cannabis use disorder score ≥12 on the Cannabis Use Disorders Identification Test (CUDIT) (28) or >1 withdrawal symptom on the Marijuana Withdrawal Checklist (MWC (29)) , major depression, manic depressive illness, schizophrenic disorders, panic disorder, generalized anxiety disorder, post-traumatic stress disorder, agoraphobia, claustrophobia, paranoid personality disorder, schizoid personality disorder, schizotypal personality disorder, borderline personality disorder, and antisocial personality disorder.)
  • History of having been treated with antidepressants, neuroleptic medications, or tranquilizers.
  • Volunteers must be drug-free (including caffeine, nicotine, alcohol and herbal medications) for the duration of the screening and study period (with the exception of THC), with no dependence on drugs (e.g. cocaine, opioids, amphetamine, methamphetamine, PCP, benzodiazepines, barbiturates, methadone, MDMA); or alcohol dependency.
  • Current Nicotine use ( or history of more than 5 'pack years' of smoking)
  • Current use of prescription or over the counter medications
  • History of shift work in the last 6 months
  • Travel across >2 time zones during the month prior to the study
  • Habitual bedtime after 1am or waketime before 5am

Sites / Locations

  • Oregon Health & Science University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Frequent Cannabis Users

Non Cannabis Users

Arm Description

Subjects categorized as frequent cannabis users (>3x/week for 3 months) will receive a single dose of 10-60mg dronabinol on the second or third night of their stay in the clinical laboratory, one hour prior to bedtime and five minutes after completion of a study snack. The other night, participants will receive a placebo. Dronabinol is an orally active, synthetic THC currently indicated for weight loss in patients with acquired immune deficiency syndrome (AIDS) or anorexia and for nausea and vomiting associated with cancer. Dronabinol is nearly absorbed (90%-95%) after a single oral dose of the capsule formulation with 10-20% of the administered dose researching the systemic circulation due to extensive first-pass hepatic metabolism and high lipid solubility. The onset of action is ~30 to 60 minutes with peak effects from 2-4-h following dose (Fig. 2) (34). The 10-60mg of dronabinol will be administered by OHSU's research pharmacy services.

Non-cannabis users (who have not used cannabis more than 10 times in their lifetime) will undergo the same single dose dronabinol and placebo as the frequent cannabis user arm, under the identical study procedure.

Outcomes

Primary Outcome Measures

Sleep Stages
Polysomnographic recordings will be measured and scored across the three sleep periods for timing and sleep stages.
Psychomotor Vigilance Change Across Four Day Inpatient Stay
Psychomotor vigilance response times (in milliseconds) will be measured shortly after awakening each test morning.
Mean Change in Response Accuracy for Paced Auditory Serial Addition Test Across Four Day Inpatient Stay
Processing speed and working memory (response accuracy) will be measured shortly after awakening each test morning. Scores can range from a minimum of 0 to 60 correct responses with each test.
Mean Change in Response Accuracy for Word Recall Across Four Day Inpatient Stay
Verbal memory will be measured shortly after awakening each test morning. Scores can range from recalling 0 words to the complete list. Participants are blinded as to list length.
Mean changes in Intoxication Levels on the Visual Analog Scale
Assessed by visual analog scale (Minimum=0, Maximum=100). 0 is "Not at all" and 100 is "Extremely". Questions ask about feeling drug effect, high right now, and wanting more of the study drug.
Blood pressure
Blood pressure (BP) will be measured every 30 min during wake and every 15 minutes during sleep. Beat-by-beat (BP) will be measured during sleep using a non-invasive device employing the volume-clamp method with hydrostatic correction (BMeye Nexfin or AD Instruments NIBP). Additionally an automated calibrated sphygmomanometer will be used to record sporadic BP at intervals during an exercise challenge.
Heart Rate
For the duration of the study, 2 channels of EKG are recorded (RA-V6) and stored at a sample frequency of 256 Hz. This software will be used for peak detection (R-wave detection and subsequent heart rate variability (HRV) analysis to estimate cardiac vagal tone).
Endothelial Function
Endothelial Function will be measured as Flow Mediated Dilation in the brachial artery 10 minutes after each awakening and 20 minutes before each sleep period.

Secondary Outcome Measures

Subjective measures of sleepiness/alertness
Subjective sleepiness and alertness will be measured regularly (~1/h) across wake periods during the study protocol using the Stanford Sleepiness Scale. The scale measures subjective sleepiness on a 1-5 point Likert scale with 5 indicating the highest degree of sleepiness and 1 indicating the lowest degree of sleepiness.
Caloric Intake
Participants will use a meal logging app to log all meals and beverages consumed for caloric/nutritional content and timing for a period prior to coming into the clinical laboratory.

Full Information

First Posted
February 9, 2018
Last Updated
May 18, 2023
Sponsor
Oregon Health and Science University
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1. Study Identification

Unique Protocol Identification Number
NCT03560934
Brief Title
Tetrahydrocannabinol (THC) and Sleep
Official Title
Effect of Tetrahydrocannabinol (THC) on Sleep in Humans
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
September 19, 2021 (Actual)
Study Completion Date
March 5, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oregon Health and Science University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators will test the effects of 10-60mg dronabinol (oral THC) on sleep in non-frequent and frequent cannabis users.
Detailed Description
The investigators plan to test the effects of 10-60 mg dronabinol (oral THC) on subjective (surveys) and objective (polysomnographically scored (PSG)) sleep in non-frequent and frequent cannabis users following an acclimation and baseline night of sleep. The mornings after baseline sleep and dronabinol administration, cognitive performance will also be measured and participants may also perform morning typical behaviors such as change in posture (getting out of bed/tilt test) and mild intensity physical activity. This pilot study is in healthy young adults without a history of chronic disease.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Participants are initially categorized as non-frequent or frequent cannabis users based on their cannabis use behavior and then receive the same treatment of 10-60mg dronabinol upon participation in the study.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Frequent Cannabis Users
Arm Type
Experimental
Arm Description
Subjects categorized as frequent cannabis users (>3x/week for 3 months) will receive a single dose of 10-60mg dronabinol on the second or third night of their stay in the clinical laboratory, one hour prior to bedtime and five minutes after completion of a study snack. The other night, participants will receive a placebo. Dronabinol is an orally active, synthetic THC currently indicated for weight loss in patients with acquired immune deficiency syndrome (AIDS) or anorexia and for nausea and vomiting associated with cancer. Dronabinol is nearly absorbed (90%-95%) after a single oral dose of the capsule formulation with 10-20% of the administered dose researching the systemic circulation due to extensive first-pass hepatic metabolism and high lipid solubility. The onset of action is ~30 to 60 minutes with peak effects from 2-4-h following dose (Fig. 2) (34). The 10-60mg of dronabinol will be administered by OHSU's research pharmacy services.
Arm Title
Non Cannabis Users
Arm Type
Experimental
Arm Description
Non-cannabis users (who have not used cannabis more than 10 times in their lifetime) will undergo the same single dose dronabinol and placebo as the frequent cannabis user arm, under the identical study procedure.
Intervention Type
Drug
Intervention Name(s)
Dronabinol
Other Intervention Name(s)
Marinol
Intervention Description
Single dose oral administration of 10-60mg dronabinol prior to night 2 or 3 sleep in the clinical laboratory.
Primary Outcome Measure Information:
Title
Sleep Stages
Description
Polysomnographic recordings will be measured and scored across the three sleep periods for timing and sleep stages.
Time Frame
Over the 3-night stay.
Title
Psychomotor Vigilance Change Across Four Day Inpatient Stay
Description
Psychomotor vigilance response times (in milliseconds) will be measured shortly after awakening each test morning.
Time Frame
Over the 3-night stay.
Title
Mean Change in Response Accuracy for Paced Auditory Serial Addition Test Across Four Day Inpatient Stay
Description
Processing speed and working memory (response accuracy) will be measured shortly after awakening each test morning. Scores can range from a minimum of 0 to 60 correct responses with each test.
Time Frame
Over the 3-night stay.
Title
Mean Change in Response Accuracy for Word Recall Across Four Day Inpatient Stay
Description
Verbal memory will be measured shortly after awakening each test morning. Scores can range from recalling 0 words to the complete list. Participants are blinded as to list length.
Time Frame
Over the 3-night stay.
Title
Mean changes in Intoxication Levels on the Visual Analog Scale
Description
Assessed by visual analog scale (Minimum=0, Maximum=100). 0 is "Not at all" and 100 is "Extremely". Questions ask about feeling drug effect, high right now, and wanting more of the study drug.
Time Frame
Over the 3-night stay.
Title
Blood pressure
Description
Blood pressure (BP) will be measured every 30 min during wake and every 15 minutes during sleep. Beat-by-beat (BP) will be measured during sleep using a non-invasive device employing the volume-clamp method with hydrostatic correction (BMeye Nexfin or AD Instruments NIBP). Additionally an automated calibrated sphygmomanometer will be used to record sporadic BP at intervals during an exercise challenge.
Time Frame
Over the 3-night stay.
Title
Heart Rate
Description
For the duration of the study, 2 channels of EKG are recorded (RA-V6) and stored at a sample frequency of 256 Hz. This software will be used for peak detection (R-wave detection and subsequent heart rate variability (HRV) analysis to estimate cardiac vagal tone).
Time Frame
Over the 3-night stay.
Title
Endothelial Function
Description
Endothelial Function will be measured as Flow Mediated Dilation in the brachial artery 10 minutes after each awakening and 20 minutes before each sleep period.
Time Frame
Over the 3-night stay.
Secondary Outcome Measure Information:
Title
Subjective measures of sleepiness/alertness
Description
Subjective sleepiness and alertness will be measured regularly (~1/h) across wake periods during the study protocol using the Stanford Sleepiness Scale. The scale measures subjective sleepiness on a 1-5 point Likert scale with 5 indicating the highest degree of sleepiness and 1 indicating the lowest degree of sleepiness.
Time Frame
Over the 3-night stay.
Title
Caloric Intake
Description
Participants will use a meal logging app to log all meals and beverages consumed for caloric/nutritional content and timing for a period prior to coming into the clinical laboratory.
Time Frame
Over the 3-night stay.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
34 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Frequent Cannabis Use (>3x/week for the prior 3 months) or No Cannabis Use (Less than 10x ever) Exclusion Criteria: Sleep Apnea Pregnancy Diabetes Cardiovascular disease Chronic Pain History of seizures Severe Hepatic impairment Conditions associated with clinically relevant cognitive impairment Symptoms of acute or active illness (e.g., fever and leukocytosis) Evidence of psychopathology on the Beck Depression Index II (BDI-II or in a structured clinical interview with a physician History of severe psychiatric illnesses (including such as alcoholism, drug dependency including a cannabis use disorder score ≥12 on the Cannabis Use Disorders Identification Test (CUDIT) (28) or >1 withdrawal symptom on the Marijuana Withdrawal Checklist (MWC (29)) , major depression, manic depressive illness, schizophrenic disorders, panic disorder, generalized anxiety disorder, post-traumatic stress disorder, agoraphobia, claustrophobia, paranoid personality disorder, schizoid personality disorder, schizotypal personality disorder, borderline personality disorder, and antisocial personality disorder.) History of having been treated with antidepressants, neuroleptic medications, or tranquilizers. Volunteers must be drug-free (including caffeine, nicotine, alcohol and herbal medications) for the duration of the screening and study period (with the exception of THC), with no dependence on drugs (e.g. cocaine, opioids, amphetamine, methamphetamine, PCP, benzodiazepines, barbiturates, methadone, MDMA); or alcohol dependency. Current Nicotine use ( or history of more than 5 'pack years' of smoking) Current use of prescription or over the counter medications History of shift work in the last 6 months Travel across >2 time zones during the month prior to the study Habitual bedtime after 1am or waketime before 5am
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven A Shea, PhD
Organizational Affiliation
Oregon Health and Science University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Tetrahydrocannabinol (THC) and Sleep

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