Behavioral Pharmacology of THC and D-limonene

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.

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

Primary outcomes

• Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) [0-6 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 outcomes

• Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) [0-6 hours]: Peak change from baseline rating of Paranoid on the DEQ, a 100pt VAS scale with 0 being no paranoia and 100 being extreme paranoia
• Mean Peak Change From Baseline Subjective "Heart Racing" as Assessed by the Drug Effect Questionnaire (DEQ) [0-6 hours]: 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.
• Mean Peak Change From Baseline Heart Rate [0-6 hours]: Peak change from baseline in Heart Rate (bpm) measured in seated position by automated monitor

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

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

Participant flow

Outcome results

• Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) (Primary), Mean, score on a scale: Placebo -1.2 +/- 8.1; Vaporized Low THC 13.8 +/- 26.5; Vaporized High THC 18.7 +/- 25.7; Vaporized Low D-limonene -1.9 +/- 13.9; Vaporized High D-limonene -0.9 +/- 6.8; Low THC and Low D-limonene 8.7 +/- 26; High THC and Low D-limonene 19.5 +/- 22.1; Low THC and High D-limonene 10.2 +/- 14.9; High THC and High D-limonene 14 +/- 21.5; High THC and 15mg D-limonene 4.3 +/- 21.9
• Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) (Secondary), Mean, score on a scale: Placebo -0.4 +/- 1.6; Vaporized Low THC 11.1 +/- 21.7; Vaporized High THC 14.6 +/- 22.2; Vaporized Low D-limonene 1.3 +/- 4.8; Vaporized High D-limonene -0.6 +/- 2.9; Low THC and Low D-limonene 9.9 +/- 17.8; High THC and Low D-limonene 16.1 +/- 23.4; Low THC and High D-limonene 9.3 +/- 19.1; High THC and High D-limonene 7.3 +/- 14.8; High THC and 15mg D-limonene 6.3 +/- 16.9
• Mean Peak Change From Baseline Subjective "Heart Racing" as Assessed by the Drug Effect Questionnaire (DEQ) (Secondary), Mean, score on a scale: Placebo 0.1 +/- 3.1; Vaporized Low THC 25.2 +/- 28.7; Vaporized High THC 32.5 +/- 25.7; Vaporized Low D-limonene 4.3 +/- 12.1; Vaporized High D-limonene 1.1 +/- 9.6; Low THC and Low D-limonene 21.2 +/- 28.7; High THC and Low D-limonene 34 +/- 26.1; Low THC and High D-limonene 16.8 +/- 21.8; High THC and High D-limonene 23.2 +/- 21.1; High THC and 15mg D-limonene 24.5 +/- 25.8
• Mean Peak Change From Baseline Heart Rate (Secondary), Mean, Beats per minute: Placebo 0.8 +/- 17.6; Vaporized Low THC 17 +/- 21; Vaporized High THC 24.8 +/- 23.1; Vaporized Low D-limonene -0.4 +/- 12.7; Vaporized High D-limonene -1.1 +/- 13.7; Low THC and Low D-limonene 19.5 +/- 25.3; High THC and Low D-limonene 24.1 +/- 24.7; Low THC and High D-limonene 19.6 +/- 19.9; High THC and High D-limonene 28.5 +/- 9.5; High THC and 15mg D-limonene 27.8 +/- 14.2

Adverse events

Time frame: 0-6 hours

Other adverse events by term

• Study Protocol (PDF, 2020-08-04)

• Ryan Vandrey, PhD, Principal investigator, Johns Hopkins University

NIH grants: R01DA043475