Trial Outcomes & Findings for Behavioral Pharmacology of THC and D-limonene (NCT NCT03609853)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

53 participants

Primary outcome timeframe

0-6 hours

Results posted on

2023-12-11

Participant Flow

This was a within-subjects design, so all participants were exposed to all 10 conditions in a randomized order.

Participant milestones

Participant milestones
Measure	Vaporized Delta-9-tetrahydrocannabinol (THC) With and Without Limonene Participants vaporized THC and limonene in a within-subject crossover design: 1. Placebo 2. Low THC (15mg) 3. High THC (30mg) 4. Low Limonene (1mg) 5. High Limonene (5mg) 6. Low THC (15mg) + low Limonene (1mg) 7. High THC (30mg) + low Limonene (1mg) 8. Low THC (15mg) + high Limonene (5mg) 9. High THC (30mg) + high Limonene (5mg) 10. High THC (30mg) + 15mg Limonene
Overall Study STARTED	35
Overall Study Placebo	28
Overall Study Vaporized Low Delta-9-tetrahydrocannabinol (THC)	25
Overall Study Vaporized High THC	27
Overall Study Vaporized Low D-limonene	30
Overall Study Vaporized High D-limonene	27
Overall Study Low THC and Low D-limonene	27
Overall Study High THC and Low D-limonene	31
Overall Study Low THC and High D-limonene	25
Overall Study High THC and High D-limonene	26
Overall Study High THC and 15mg Limonene	12
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Behavioral Pharmacology of THC and D-limonene

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vaporized THC With and Without Limonene n=20 Participants 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
Age, Continuous	26 years n=93 Participants
Sex: Female, Male Female	10 Participants n=93 Participants
Sex: Female, Male Male	10 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	7 Participants n=93 Participants
Race (NIH/OMB) White	9 Participants n=93 Participants
Race (NIH/OMB) More than one race	4 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: 0-6 hours

Population: Represents study completers

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

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo (5mL distilled water) Placebo: Placebo vapor (distilled water)	Vaporized Low THC n=20 Participants 15mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High THC n=20 Participants 30mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized Low D-limonene n=20 Participants 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High D-limonene n=20 Participants 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and Low D-limonene n=20 Participants 15mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and Low D-limonene n=20 Participants 30mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and High D-limonene n=20 Participants 15mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and High D-limonene n=20 Participants 30mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and 15mg D-limonene n=12 Participants 30mg of THC paired with 15mg of d-limonene
Mean Peak Change From Baseline Anxiety as Assessed by the Drug Effect Questionnaire (DEQ)	-1.2 score on a scale Standard Deviation 8.1	13.8 score on a scale Standard Deviation 26.5	18.7 score on a scale Standard Deviation 25.7	-1.9 score on a scale Standard Deviation 13.9	-0.9 score on a scale Standard Deviation 6.8	8.7 score on a scale Standard Deviation 26	19.5 score on a scale Standard Deviation 22.1	10.2 score on a scale Standard Deviation 14.9	14 score on a scale Standard Deviation 21.5	4.3 score on a scale Standard Deviation 21.9

SECONDARY outcome

Timeframe: 0-6 hours

Population: Study completers

Peak change from baseline rating of Paranoid on the DEQ, a 100pt VAS scale with 0 being no paranoia and 100 being extreme paranoia

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo (5mL distilled water) Placebo: Placebo vapor (distilled water)	Vaporized Low THC n=20 Participants 15mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High THC n=20 Participants 30mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized Low D-limonene n=20 Participants 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High D-limonene n=20 Participants 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and Low D-limonene n=20 Participants 15mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and Low D-limonene n=20 Participants 30mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and High D-limonene n=20 Participants 15mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and High D-limonene n=20 Participants 30mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and 15mg D-limonene n=12 Participants 30mg of THC paired with 15mg of d-limonene
Mean Peak Change From Baseline Paranoid as Assessed by the Drug Effect Questionnaire (DEQ)	-0.4 score on a scale Standard Deviation 1.6	11.1 score on a scale Standard Deviation 21.7	14.6 score on a scale Standard Deviation 22.2	1.3 score on a scale Standard Deviation 4.8	-0.6 score on a scale Standard Deviation 2.9	9.9 score on a scale Standard Deviation 17.8	16.1 score on a scale Standard Deviation 23.4	9.3 score on a scale Standard Deviation 19.1	7.3 score on a scale Standard Deviation 14.8	6.3 score on a scale Standard Deviation 16.9

SECONDARY outcome

Timeframe: 0-6 hours

Population: Study completers

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.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo (5mL distilled water) Placebo: Placebo vapor (distilled water)	Vaporized Low THC n=20 Participants 15mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High THC n=20 Participants 30mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized Low D-limonene n=20 Participants 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High D-limonene n=20 Participants 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and Low D-limonene n=20 Participants 15mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and Low D-limonene n=20 Participants 30mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and High D-limonene n=20 Participants 15mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and High D-limonene n=20 Participants 30mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and 15mg D-limonene n=12 Participants 30mg of THC paired with 15mg of d-limonene
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	25.2 score on a scale Standard Deviation 28.7	32.5 score on a scale Standard Deviation 25.7	4.3 score on a scale Standard Deviation 12.1	1.1 score on a scale Standard Deviation 9.6	21.2 score on a scale Standard Deviation 28.7	34 score on a scale Standard Deviation 26.1	16.8 score on a scale Standard Deviation 21.8	23.2 score on a scale Standard Deviation 21.1	24.5 score on a scale Standard Deviation 25.8

SECONDARY outcome

Timeframe: 0-6 hours

Population: Study completers

Peak change from baseline in Heart Rate (bpm) measured in seated position by automated monitor

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo (5mL distilled water) Placebo: Placebo vapor (distilled water)	Vaporized Low THC n=20 Participants 15mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High THC n=20 Participants 30mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized Low D-limonene n=20 Participants 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High D-limonene n=20 Participants 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and Low D-limonene n=20 Participants 15mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and Low D-limonene n=20 Participants 30mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and High D-limonene n=20 Participants 15mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and High D-limonene n=20 Participants 30mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and 15mg D-limonene n=12 Participants 30mg of THC paired with 15mg of d-limonene
Mean Peak Change From Baseline Heart Rate	0.8 Beats per minute Standard Deviation 17.6	17 Beats per minute Standard Deviation 21	24.8 Beats per minute Standard Deviation 23.1	-0.4 Beats per minute Standard Deviation 12.7	-1.1 Beats per minute Standard Deviation 13.7	19.5 Beats per minute Standard Deviation 25.3	24.1 Beats per minute Standard Deviation 24.7	19.6 Beats per minute Standard Deviation 19.9	28.5 Beats per minute Standard Deviation 9.5	27.8 Beats per minute Standard Deviation 14.2

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=28 participants at risk Placebo (5mL distilled water) Placebo: Placebo vapor (distilled water)	Vaporized Low THC n=25 participants at risk 15mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High THC n=27 participants at risk 30mg of pure THC Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized Low D-limonene n=30 participants at risk 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Vaporized High D-limonene n=27 participants at risk 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and Low D-limonene n=27 participants at risk 15mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and Low D-limonene n=31 participants at risk 30mg of THC paired with 1mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	Low THC and High D-limonene n=25 participants at risk 15mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and High D-limonene n=26 participants at risk 30mg of THC paired with 5mg of d-limonene Vaporized THC, limonene, or THC and limonene: Acute drug exposure	High THC and 15mg D-limonene n=12 participants at risk 30mg of THC paired with 15mg of d-limonene
Nervous system disorders Dizziness	0.00% 0/28 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	7.4% 2/27 • Number of events 2 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/30 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	3.2% 1/31 • Number of events 1 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/26 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/12 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.
Social circumstances Intrusive Anxiety	0.00% 0/28 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	4.0% 1/25 • Number of events 1 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	3.7% 1/27 • Number of events 1 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/30 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	6.5% 2/31 • Number of events 2 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/26 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/12 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.
Vascular disorders Lightheaded	0.00% 0/28 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	6.7% 2/30 • Number of events 2 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	6.5% 2/31 • Number of events 2 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	7.7% 2/26 • Number of events 2 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/12 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.
Gastrointestinal disorders Nausea	0.00% 0/28 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/30 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	9.7% 3/31 • Number of events 3 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/26 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/12 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.
Vascular disorders Tachycardia	0.00% 0/28 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	4.0% 1/25 • Number of events 1 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	11.1% 3/27 • Number of events 3 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/30 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/27 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	11.1% 3/27 • Number of events 3 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	9.7% 3/31 • Number of events 3 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/25 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/26 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.	0.00% 0/12 • 0-6 hours International Council for Harmonisation (ICH) guidelines are followed for Adverse Event (AE) reporting, as AEs occur they are documented.

Additional Information

Dr. Ryan Vandrey

Johns Hopkins School of Medicine

Phone: 410-550-4036

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place