D-limonene and THC Pharmacodynamics
Conditions
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.
Interventions
DRUGPlacebo
Placebo vapor (distilled water)
DRUGVaporized THC, limonene, or THC and limonene
Acute drug exposure
Sponsors
National Institute on Drug Abuse (NIDA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
placebo controlled, double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Pre-assignment details
This was a within-subjects design, so all participants were exposed to all 10 conditions in a randomized order.
Participants by arm
| Arm | Count |
|---|---|
| Vaporized THC With and Without Limonene All study completers completed the following 10 conditions in a randomized order:
1. Placebo (distilled water)
2. Vaporized Low THC (15mg)
3. Vaporized High THC (30mg)
4. Vaporized Low d-Limonene (1mg)
5. Vaporized High d-Limonene (5mg)
6. Vaporized Low THC + low d-Limonene
7. Vaporized High THC + low d-Limonene
8. Vaporized Low THC + high d-Limonene
9. Vaporized High THC + high d-Limonene
10. Vaporized High THC + 15mg d-Limonene | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Vaporized THC With and Without Limonene |
|---|---|
| Age, Continuous | 26 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 25 | 0 / 27 | 0 / 30 | 0 / 27 | 0 / 27 | 0 / 31 | 0 / 25 | 0 / 26 | 0 / 12 |
| other Total, other adverse events | 0 / 28 | 1 / 25 | 3 / 27 | 2 / 30 | 0 / 27 | 3 / 27 | 4 / 31 | 0 / 25 | 2 / 26 | 0 / 12 |
| serious Total, serious adverse events | 0 / 28 | 0 / 25 | 0 / 27 | 0 / 30 | 0 / 27 | 0 / 27 | 0 / 31 | 0 / 25 | 0 / 26 | 0 / 12 |
Outcome results
Primary
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
Time frame: 0-6 hours
Population: Represents study completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | -1.2 score on a scale | Standard Deviation 8.1 |
| Vaporized Low THC | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | 13.8 score on a scale | Standard Deviation 26.5 |
| Vaporized High THC | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | 18.7 score on a scale | Standard Deviation 25.7 |
| Vaporized Low D-limonene | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | -1.9 score on a scale | Standard Deviation 13.9 |
| Vaporized High D-limonene | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | -0.9 score on a scale | Standard Deviation 6.8 |
| Low THC and Low D-limonene | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | 8.7 score on a scale | Standard Deviation 26 |
| High THC and Low D-limonene | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | 19.5 score on a scale | Standard Deviation 22.1 |
| Low THC and High D-limonene | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | 10.2 score on a scale | Standard Deviation 14.9 |
| High THC and High D-limonene | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | 14 score on a scale | Standard Deviation 21.5 |
| High THC and 15mg D-limonene | Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ) | 4.3 score on a scale | Standard Deviation 21.9 |
Secondary
Mean Peak Change From Baseline Heart Rate
Peak change from baseline in Heart Rate (bpm) measured in seated position by automated monitor
Time frame: 0-6 hours
Population: Study completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Peak Change From Baseline Heart Rate | 0.8 Beats per minute | Standard Deviation 17.6 |
| Vaporized Low THC | Mean Peak Change From Baseline Heart Rate | 17 Beats per minute | Standard Deviation 21 |
| Vaporized High THC | Mean Peak Change From Baseline Heart Rate | 24.8 Beats per minute | Standard Deviation 23.1 |
| Vaporized Low D-limonene | Mean Peak Change From Baseline Heart Rate | -0.4 Beats per minute | Standard Deviation 12.7 |
| Vaporized High D-limonene | Mean Peak Change From Baseline Heart Rate | -1.1 Beats per minute | Standard Deviation 13.7 |
| Low THC and Low D-limonene | Mean Peak Change From Baseline Heart Rate | 19.5 Beats per minute | Standard Deviation 25.3 |
| High THC and Low D-limonene | Mean Peak Change From Baseline Heart Rate | 24.1 Beats per minute | Standard Deviation 24.7 |
| Low THC and High D-limonene | Mean Peak Change From Baseline Heart Rate | 19.6 Beats per minute | Standard Deviation 19.9 |
| High THC and High D-limonene | Mean Peak Change From Baseline Heart Rate | 28.5 Beats per minute | Standard Deviation 9.5 |
| High THC and 15mg D-limonene | Mean Peak Change From Baseline Heart Rate | 27.8 Beats per minute | Standard Deviation 14.2 |
Secondary
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
Time frame: 0-6 hours
Population: Study completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | -0.4 score on a scale | Standard Deviation 1.6 |
| Vaporized Low THC | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 11.1 score on a scale | Standard Deviation 21.7 |
| Vaporized High THC | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 14.6 score on a scale | Standard Deviation 22.2 |
| Vaporized Low D-limonene | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 1.3 score on a scale | Standard Deviation 4.8 |
| Vaporized High D-limonene | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | -0.6 score on a scale | Standard Deviation 2.9 |
| Low THC and Low D-limonene | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 9.9 score on a scale | Standard Deviation 17.8 |
| High THC and Low D-limonene | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 16.1 score on a scale | Standard Deviation 23.4 |
| Low THC and High D-limonene | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 9.3 score on a scale | Standard Deviation 19.1 |
| High THC and High D-limonene | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 7.3 score on a scale | Standard Deviation 14.8 |
| High THC and 15mg D-limonene | Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ) | 6.3 score on a scale | Standard Deviation 16.9 |
Secondary
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.
Time frame: 0-6 hours
Population: Study completers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 0.1 score on a scale | Standard Deviation 3.1 |
| Vaporized Low THC | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 25.2 score on a scale | Standard Deviation 28.7 |
| Vaporized High THC | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 32.5 score on a scale | Standard Deviation 25.7 |
| Vaporized Low D-limonene | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 4.3 score on a scale | Standard Deviation 12.1 |
| Vaporized High D-limonene | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 1.1 score on a scale | Standard Deviation 9.6 |
| Low THC and Low D-limonene | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 21.2 score on a scale | Standard Deviation 28.7 |
| High THC and Low D-limonene | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 34 score on a scale | Standard Deviation 26.1 |
| Low THC and High D-limonene | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 16.8 score on a scale | Standard Deviation 21.8 |
| High THC and High D-limonene | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 23.2 score on a scale | Standard Deviation 21.1 |
| High THC and 15mg D-limonene | Mean Peak Change From Baseline Subjective Heart Racing as Assessed by the Drug Effect Questionnaire (DEQ) | 24.5 score on a scale | Standard Deviation 25.8 |