Behavioral Pharmacology of THC and D-limonene

This study will evaluate the pharmacokinetics and pharmacodynamics of vaporized d-limonene and THC administered via inhalation.

Study Overview

• Status: Completed
• Conditions: D-limonene and THC Pharmacodynamics
• Intervention / Treatment: Drug: Placebo; Drug: Vaporized THC, limonene, or THC and limonene

Detailed Description

The proposed study will be conducted at the Johns Hopkins Behavioral Pharmacology Research Unit (BPRU). Participants will complete 9 acute drug administration periods in which they will administer THC alone, limonene alone, THC and limonene together, or placebo. Subjective drug effects and vital signs will be assessed following drug administration. Each participant will receive all 9 dose conditions in a randomized order using a placebo controlled within-subject crossover design. The study will help us understand the individual and interactive effects of THC and d-limonene, two common constituents found in cannabis.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Behavioral Pharmacology Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Have provided written informed consent
2. Be between the ages of 18 and 55
3. Be in good general health based on a physical examination, medical history, vital signs, 12-lead ECG and screening urine and blood tests
4. Test negative for drugs of abuse other than cannabis, including breath alcohol at the screening visit and at clinic admission
5. Not be pregnant or nursing (if female). All females must have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at clinic admission.
6. Have a body mass index (BMI) in the range of 18 to 36 kg/m2
7. Blood pressure at Screening Visit does not exceed a systolic blood pressure (SBP) of 150 mmHg or a diastolic blood pressure (DBP) of 90 mmHg
8. Have no allergies to any of the ingredients used to prepare vapor (THC, d-limonene).
9. Report having experienced anxiety after consuming cannabis in the past.

Exclusion Criteria:

1. Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine 3 month prior to the Screening Visit;
2. History of or current evidence of significant medical (e.g. seizure disorder) or psychiatric illness (e.g. psychosis) judged by the investigator to put the participant at greater risk of experiencing an adverse event due to exposure or completion of other study procedures.
3. Use of an over the counter, systemic or topical drug(s), herbal supplement(s), or vitamin(s) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject.
4. Use of a prescription medication (with the exception of birth control prescriptions) within 14 days of experimental sessions; which, in the opinion of the investigator or sponsor, will interfere with the study result or the safety of the subject.
5. Use of dronabinol (Marinol®) within the past month.
6. Average use of cannabis more than 2 times per week in the prior 3 months.
7. History of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina).
8. Abnormal EKG result that in the investigator's opinion is clinically significant.
9. Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing.
10. Having previously sought medical attention to manage adverse effects following acute cannabis use.
11. Individuals with anemia or who have donated blood in the prior 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (5mL distilled water)	Drug: Placebo; Placebo vapor (distilled water)
Experimental: Vaporized low THC; 15mg of pure THC	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: Vaporized high THC; 30mg of pure THC	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: Vaporized low d-limonene; 1mg of d-limonene	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: Vaporized high d-limonene; 5mg of d-limonene	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: Low THC and low d-limonene; 15mg of THC paired with 1mg of d-limonene	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: High THC and low d-limonene; 30mg of THC paired with 1mg of d-limonene	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: Low THC and high d-limonene; 15mg of THC paired with 5mg of d-limonene	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: High THC and high d-limonene; 30mg of THC paired with 5mg of d-limonene	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure
Experimental: High THC and 15mg d-limonene; 30mg of THC paired with 15mg of d-limonene	Drug: Vaporized THC, limonene, or THC and limonene; Acute drug exposure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ)	Peak rating (0-100) of Anxiety on the DEQ, a visual analog scale (VAS) self-report questionnaire with 0 being No anxiety and 100 being maximum anxiety	0-6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ)	Peak change from baseline rating of Paranoid on the DEQ, a 100pt VAS scale with 0 being no paranoia and 100 being extreme paranoia	0-6 hours
Mean Peak Change From Baseline Heart Rate	Peak change from baseline in Heart Rate (bpm) measured in seated position by automated monitor	0-6 hours
Mean Peak Change From Baseline Subjective "Heart Racing" as Assessed by the Drug Effect Questionnaire (DEQ)	Mean peak change from baseline for subjective heart racing on the DEQ, a 0-100 VAS scale with 0 being no feeling of heart racing and 100 being an extreme feeling of heart racing.	0-6 hours

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Ryan Vandrey, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Actual): June 28, 2022
• Study Completion (Actual): October 25, 2023

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): August 1, 2018

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: IRB00085652; R01DA043475 (U.S. NIH Grant/Contract)

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