Behavioral Pharmacology of THC and D-limonene

• ClinicalTrials.gov Identifier: NCT03609853
• Recruitment Status: Recruiting
• First Posted: August 1, 2018
• Last Update Posted: January 13, 2021
• Sponsor: Johns Hopkins University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Johns Hopkins University

Tracking Information

• First Submitted Date: July 11, 2018
• First Posted Date: August 1, 2018
• Last Update Posted Date: January 13, 2021
• Actual Study Start Date: April 1, 2019
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 25, 2018)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 25, 2018)

• 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
• 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
• Change in Heart Rate [ Time Frame: 6 hours ]
  Peak change from baseline in Heart Rate (bpm) measured in seated position by automated monitor

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Behavioral Pharmacology of THC and D-limonene
• Official Title: Behavioral Pharmacology of THC and D-limonene
• Brief Summary: This study will evaluate the pharmacokinetics and pharmacodynamics of vaporized d-limonene and THC administered via inhalation.
• 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
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Masking Description:

placebo controlled, double-blind

Primary Purpose: Basic Science

• Condition: D-limonene and THC Pharmacodynamics

Intervention

• Drug: Placebo
  Placebo vapor (distilled water)
• Drug: Vaporized THC, limonene, or THC and limonene
  Acute drug exposure

Study Arms

• Placebo Comparator: Placebo
  Placebo (5mL distilled water)
  Intervention: Drug: Placebo
• Experimental: Vaporized low THC
  15mg of pure THC
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene
• Experimental: Vaporized high THC
  30mg of pure THC
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene
• Experimental: Vaporized low d-limonene
  1mg of d-limonene
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene
• Experimental: Vaporized high d-limonene
  5mg of d-limonene
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene
• Experimental: Low THC and low d-limonene
  15mg of THC paired with 1mg of d-limonene
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene
• Experimental: High THC and low d-limonene
  30mg of THC paired with 1mg of d-limonene
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene
• Experimental: Low THC and high d-limonene
  15mg of THC paired with 5mg of d-limonene
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene
• Experimental: High THC and high d-limonene
  30mg of THC paired with 5mg of d-limonene
  Intervention: Drug: Vaporized THC, limonene, or THC and limonene

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 25, 2018): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2022
• Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03609853
• Other Study ID Numbers: IRB00085652; R01DA043475 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Johns Hopkins University
• Study Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)

Investigators

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

• PRS Account: Johns Hopkins University
• Verification Date: January 2021