Differential Female Response to Δ9-tetrahydrocannabinol (THC)
Conditions
Brief summary
Females are increasingly using cannabis, yet remain underrepresented in preclinical and clinical cannabinoid research. This female-specific research plan will test the effects of two recreationally relevant doses of oral THC and placebo in healthy females at two phases of the menstrual cycle. Acute oral THC will be administered in a double-blind and counterbalanced design. Menstrual cycle phase will be determined using blood serum analyses of estradiol and progesterone and self-reported responses. The main hypothesis is circulating estradiol levels are associated with cardiac, neuroendocrine, and subjective THC response. The rationale for the presented work is to better understand the risks of cannabis use, in order to maximize possible medical potential and minimize public health risks. The expected outcome of this work is a deeper understanding of how circulating estradiol levels may associate with response to THC and how the physiological response is associated with the subjective response. Uncovering the individual differences in response to THC will allow for more preventive action against cannabis-induced anxiety, paranoia, and psychosis.
Interventions
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 (Ménétrey et al., 2005; Issa et al. 2016).
DRUGdextrose
We are administering dextrose to health volunteers for our placebo group
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
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-35 years old, females (N=60) * Body Mass Index 19-26 * High school education, fluent in English * Occasional cannabis users ( \<11 times in past 30 days)
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 * Past year major depression * Current or past Post Traumatic Stress Disorder * Attention Deficit Hyperactivity Disorder * Cardiovascular illness, high blood pressure, abnormal electrocardiagram * Current medications (NO hormonal birth control or intrauterine device) * Pregnant or planning to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Profile of Mood States (POMS) | Difference from baseline (time 0 or pre-capsule) to post-capsule (120 min) | The POMS measures individuals' mood states. This is a validated scale to measure positive and negative mood states. The POMS contains 30 items and assess six identified mood factors: Tension-Anxiety, Depression-Ejection, Anger - Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. Scoring of this instrument provides a global score of 0 to 120 or individual domain scores. Subscale scores range from 0-20. 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: We are administering dextrose to health volunteers for our placebo group | 20 |
| 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 (Ménétrey et al., 2005; Issa et al. 2016). | 20 |
| 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 (Ménétrey et al., 2005; Issa et al. 2016). | 20 |
| Total | 60 |
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 | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| High School Education | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 3 Participants | 9 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 | 14 Participants | 14 Participants | 14 Participants | 42 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 20 participants | 60 participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 |
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 contains 30 items and assess six identified mood factors: Tension-Anxiety, Depression-Ejection, Anger - Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. Scoring of this instrument provides a global score of 0 to 120 or individual domain scores. Subscale scores range from 0-20. Lower scores indicate better mood state. The POMS brief form is a simple self-rating instrument.
Time frame: Difference from baseline (time 0 or pre-capsule) to post-capsule (120 min)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Profile of Mood States (POMS) | Tension - Anxiety | 2.58 units on a scale | Standard Deviation 0.047 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | Depression - Ejection | 0.7 units on a scale | Standard Deviation 0.005 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | Anger - Hostility | 1.2 units on a scale | Standard Deviation 0.01 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | Vigor - Activity | 5.02 units on a scale | Standard Deviation 0.04 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | Fatigue - Inertia | 2.0 units on a scale | Standard Deviation 0.11 |
| Placebo | Change From Baseline in Profile of Mood States (POMS) | Confusion - Bewilderment | 2.0 units on a scale | Standard Deviation 0.065 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | Confusion - Bewilderment | 2.25 units on a scale | Standard Deviation 0.055 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | Tension - Anxiety | 4.28 units on a scale | Standard Deviation 0.07 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | Vigor - Activity | 7.5 units on a scale | Standard Deviation 0.05 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | Fatigue - Inertia | 3.75 units on a scale | Standard Deviation 0.04 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | Depression - Ejection | 1.2 units on a scale | Standard Deviation 0.02 |
| 7.5 mg THC | Change From Baseline in Profile of Mood States (POMS) | Anger - Hostility | 1.5 units on a scale | Standard Deviation 0.025 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | Depression - Ejection | 1.04 units on a scale | Standard Deviation 0.004 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | Anger - Hostility | 4.25 units on a scale | Standard Deviation 0.036 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | Confusion - Bewilderment | 3.25 units on a scale | Standard Deviation 0.04 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | Vigor - Activity | 6.25 units on a scale | Standard Deviation 0.09 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | Tension - Anxiety | 8.25 units on a scale | Standard Deviation 0.05 |
| 15 mg THC | Change From Baseline in Profile of Mood States (POMS) | Fatigue - Inertia | 7.25 units on a scale | Standard Deviation 0.01 |