Individual Differences in Drug Response

Study Overview
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Brief Summary
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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.

Official Title
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Differential Female Response to Δ9-tetrahydrocannabinol (THC): The Influence of Estradiol

Conditions
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Differential Female Response to Δ9-tetrahydrocannabinol (THC)

Intervention / Treatment
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* Drug: Dronabinol
* Drug: dextrose


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: dextrose<br>* We are administering dextrose to health volunteers for our placebo group<br>|
| Active Comparator: 7.5 mg THC<br> | Drug: Dronabinol<br>* 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).<br>|
| Active Comparator: 15 mg THC<br> | Drug: Dronabinol<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. Lower scores indicate better mood state. The POMS brief form is a simple self-rating instrument | End of session (Baseline - time 0 or pre-capsule, post-capsule) | 
| State Anxiety Inventory | This scale measures both trait and state anxiety levels and will be administered separately. Responses for 20 trait anxiety symptom items are recorded on a 4-point Likert scale from almost never (1) to almost always (4). Range of scores is 20-80, the higher score indicating greater trait anxiety. This measure will be used to obtain baseline trait ratings of anxiety during the orientation session. The state scale contains 20 items to measure state anxiety symptoms. Participants indicate the intensity of their state feelings on a 4-point scale from not at all (1) to very much so (4). | End of session (Baseline - time 0 or pre-capsule, post-capsule) | 
| Heart Rate Variability and Thoracic Impedance | ECG and thoracic impedance measures will be amplified and processed by an integrated Mindware Bionex system (Mindware, Gahanna, OH). Respiratory sinus arrhythmia will be analyzed from the data as the measure of parasympathetic cardiac control. Pre-ejection period will be analyzed from the data as the measure of sympathetic cardiac control. | End of session (Baseline - time 0 or pre-capsule, post-capsule) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Effects Questionnaire | This questionnaire consists of 5 visual analogue scales measuring subjective drug effects. Participants indicate their response on a scale of 0-100: Do you feel any drug effect? (rated from none at all to a lot), Do you like the effects you are feeling now? (rated from not at all to very much), Do you dislike the effects you are feeling now? (rated from not at all to very much), Are you high? (rated from not at all to very much), and Would you like more of what you consumed, right now? (rated from not at all to very much). This measure will be used as another manipulation check to ensure the drug produced subjective effects, but it is not be specific to a certain drug class. | End of session (Baseline - time 0 or pre-capsule, post-capsule) |