Behavioral Pharmacology of THC and D-limonene

• ClinicalTrials.gov Identifier: NCT03609853
• Recruitment Status: Recruiting
• First Posted: August 1, 2018
• Last Update Posted: June 22, 2022
• Sponsor: Johns Hopkins University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
D-limonene and THC Pharmacodynamics	Drug: Placebo; Drug: Vaporized THC, limonene, or THC and limonene	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: placebo controlled, double-blind
• Primary Purpose: Basic Science
• Official Title: Behavioral Pharmacology of THC and D-limonene
• Actual Study Start Date: April 1, 2019
• Estimated Primary Completion Date: September 1, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Level of Anxiety as assessed by the Drug Effect Questionnaire (DEQ) [ Time Frame: 6 hours ]
   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

Secondary Outcome Measures :

1. Level of Unpleasant Effect as assessed by the Drug Effect Questionnaire (DEQ) [ Time Frame: 6 hours ]
   Peak rating (0-100) of Unpleasant Effect on the DEQ, with 0 being no unpleasant effect and 100 being worst unpleasant effect
2. Difficulty in Performing Routine Tasks as assessed the Drug Effect Questionnaire (DEQ) [ Time Frame: 6 hours ]
   Peak rating (0-100) of Difficulty Performing Routine Tasks on the DEQ, 0 being no difficulty and 100 being inability to perform task all together
3. Change in Heart Rate [ Time Frame: 6 hours ]
   Peak change from baseline in Heart Rate (bpm) measured in seated position by automated monitor

Eligibility Criteria

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

Criteria

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 OTC, 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

Contacts and Locations

Contacts

Contact: Joshua Elmore; 410-550-9491; jelmore4@jhmi.edu

Locations

United States, Maryland

Johns Hopkins Behavioral Pharmacology Research Unit; Recruiting

Baltimore, Maryland, United States, 21224

Contact: Ryan Vandrey

Principal Investigator: Ryan Vandrey, PhD

Sponsors and Collaborators

Johns Hopkins University

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Ryan Vandrey, PhD; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03609853
• Other Study ID Numbers: IRB00085652; R01DA043475 ( U.S. NIH Grant/Contract )
• First Posted: August 1, 2018
• Last Update Posted: June 22, 2022
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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