Individual Differences in Drug Response (IDT)

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

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.

Study Overview

• Status: Completed
• Conditions: Differential Female Response to Δ9-tetrahydrocannabinol (THC)
• Intervention / Treatment: Drug: Dronabinol; Drug: dextrose

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60615
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: dextrose; We are administering dextrose to health volunteers for our placebo group
ACTIVE_COMPARATOR: 7.5 mg THC	Drug: 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).
ACTIVE_COMPARATOR: 15 mg THC	Drug: 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).

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Chicago

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 6, 2018
• Primary Completion (ACTUAL): June 1, 2021
• Study Completion (ACTUAL): June 1, 2021

Study Registration Dates

• First Submitted: January 11, 2019
• First Submitted That Met QC Criteria: January 15, 2019
• First Posted (ACTUAL): January 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: June 8, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: IDT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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.: No