Adolescent Behavior, THC, Tolerance
Conditions
Brief summary
Increased accessibility to cannabis and its primary psychoactive constituent THC has raised public health concerns. One major concern surrounds the potential risks associated with acute THC intoxication and who might be most at risk. A second major concern is the need to develop sensitive measures that can detect THC intoxication after recent use and enable robust comparisons of intoxication to determine sources of risk. One potential source of risk is age, specifically during the period of adolescence.
Detailed description
There is limited knowledge on the effects of THC in adolescents vs adults. One recent report compared responses to vaporized cannabis in heavy adolescent vs adult cannabis users and found that the adolescents were less sensitive to the drug on most measures. However, their findings were complicated by several factors: i) the study used vaporized cannabis, which may have other constituents and does not offer full control of the dose, ii) the participants were heavy users, making it difficult to determine the influence of prior drug exposure, and iii) the participants were not drug-free at the time of testing. Prior exposure to THC can lead to tolerance, and adolescents and adults may differ in the rate at which they develop tolerance, consistent with changes in CB1R receptor function. Our study will compare adolescent (here, aged 18 to 20) and adult (here, aged 30 to 40) responses to THC in relatively light cannabis users who are drug-free at the time of testing.
Interventions
DRUGDextrose
Administering dextrose to healthy volunteers for our placebo group
DRUGDronabinol
THC (Marinol® \[dronabinol\]; Solvay Pharmaceuticals) will be orally administered in doses of 7.5 mg and 15 mg, in opaque capsules with dextrose filler. Placebo capsules contain only dextrose. These doses of THC are known to produce performance impairments as well as subjective intoxication with little to no adverse reactions in experienced occasional, but non-daily cannabis users.
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-20 years old OR 30-40 years old * Body Mass Index 19-26 * High school education, fluent in English * Occasional cannabis users ( 0 times in past 30 days AND used cannabis no more than 20 times in lifetime)
Exclusion criteria
* History of daily cannabis use * Past or present severe substance use disorder * Current or past diagnosis with drug treatment for psychosis/bipolar/schizophrenia * Cardiovascular illness, high blood pressure, abnormal electrocardiogram * Current medications * Pregnant or planning to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Profile of Mood States (POMS) | Through Study Completion, an average of 3 weeks (Baseline - time 0 to Time point 9 (Study Completion)) | The POMS measures individuals' mood states. This is a validated scale to measure positive and negative mood states. The POMS consists of 72 mood adjectives rated on a Likert scale from 0 (not at all) to 4 (extremely), divided into 8 subscales: Friendliness, Anxiety, Elation, Anger, Fatigue, Depression, Confusion and Vigor, and two composite scales: Positive Mood (Elation minus Depression) and Arousal (Vigor plus Anxiety minus Confusion plus Fatigue). Scoring of this instrument provides a global score of 0 to 120 or individual domain scores of 0 to 20. Lower scores indicate better mood state. The POMS brief form is a simple self-rating instrument. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dextrose: Administering dextrose to health volunteers for our placebo group | 8 |
| 7.5 mg THC Dronabinol: THC (Marinol® \[dronabinol\]; Solvay Pharmaceuticals) will be orally administered in doses of 7.5 mg and 15 mg, in opaque capsules with dextrose filler. Placebo capsules contain only dextrose. These doses of THC are known to produce performance impairments as well as subjective intoxication with little to no adverse reactions in experienced occasional, but non-daily cannabis users. | 8 |
| 15 mg THC Dronabinol: THC (Marinol® \[dronabinol\]; Solvay Pharmaceuticals) will be orally administered in doses of 7.5 mg and 15 mg, in opaque capsules with dextrose filler. Placebo capsules contain only dextrose. These doses of THC are known to produce performance impairments as well as subjective intoxication with little to no adverse reactions in experienced occasional, but non-daily cannabis users. | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo | 7.5 mg THC | 15 mg THC | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 24 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Change From Baseline in Profile of Mood States (POMS)
The POMS measures individuals' mood states. This is a validated scale to measure positive and negative mood states. The POMS consists of 72 mood adjectives rated on a Likert scale from 0 (not at all) to 4 (extremely), divided into 8 subscales: Friendliness, Anxiety, Elation, Anger, Fatigue, Depression, Confusion and Vigor, and two composite scales: Positive Mood (Elation minus Depression) and Arousal (Vigor plus Anxiety minus Confusion plus Fatigue). Scoring of this instrument provides a global score of 0 to 120 or individual domain scores of 0 to 20. Lower scores indicate better mood state. The POMS brief form is a simple self-rating instrument.
Time frame: Through Study Completion, an average of 3 weeks (Baseline - time 0 to Time point 9 (Study Completion))
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Anxiety Week 1 | 5.75 units on a scale | Standard Deviation 5.12 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Depression Week 1 | 4.08 units on a scale | Standard Deviation 3.6 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Vigor Week 1 | 13.00 units on a scale | Standard Deviation 6.03 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Fatigue Week 1 | 6.67 units on a scale | Standard Deviation 6.27 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Friendliness Week 1 | 6.42 units on a scale | Standard Deviation 3.82 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Anxiety Week 3 | 5.50 units on a scale | Standard Deviation 4.56 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Depression Week 3 | 3.92 units on a scale | Standard Deviation 6.64 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Vigor Week 3 | 16.83 units on a scale | Standard Deviation 5.92 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Fatigue Week 3 | 6.0 units on a scale | Standard Deviation 4.86 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | POMS Friendliness Week 3 | 9.42 units on a scale | Standard Deviation 5.99 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Fatigue Week 3 | 8.65 units on a scale | Standard Deviation 2.58 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Anxiety Week 1 | 12.46 units on a scale | Standard Deviation 3.56 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Anxiety Week 3 | 14.25 units on a scale | Standard Deviation 5.88 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Friendliness Week 1 | 16.25 units on a scale | Standard Deviation 5.58 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Depression Week 1 | 5.05 units on a scale | Standard Deviation 3.66 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Friendliness Week 3 | 8.22 units on a scale | Standard Deviation 2.25 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Vigor Week 3 | 6.87 units on a scale | Standard Deviation 4.25 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Vigor Week 1 | 8.05 units on a scale | Standard Deviation 2.25 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Depression Week 3 | 5.28 units on a scale | Standard Deviation 1.33 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Fatigue Week 1 | 14.25 units on a scale | Standard Deviation 6.85 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Vigor Week 3 | 6.22 units on a scale | Standard Deviation 2.22 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Fatigue Week 1 | 8.25 units on a scale | Standard Deviation 2.55 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Friendliness Week 1 | 8.25 units on a scale | Standard Deviation 2.22 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Anxiety Week 3 | 19.25 units on a scale | Standard Deviation 5.22 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Fatigue Week 3 | 6.25 units on a scale | Standard Deviation 2.55 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Depression Week 3 | 8.25 units on a scale | Standard Deviation 2.55 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Anxiety Week 1 | 18.55 units on a scale | Standard Deviation 2.55 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Friendliness Week 3 | 11.25 units on a scale | Standard Deviation 2.25 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Depression Week 1 | 6.25 units on a scale | Standard Deviation 1.05 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | POMS Vigor Week 1 | 8.25 units on a scale | Standard Deviation 4.25 |