Behavioral Pharmacology of THC and D-limonene

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

Detailed Description
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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.

Official Title
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Behavioral Pharmacology of THC and D-limonene

Conditions
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D-limonene and THC Pharmacodynamics

Intervention / Treatment
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* Drug: Placebo
* Drug: Vaporized THC, limonene, or THC and limonene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have provided written informed consent Be between the ages of 18 and 55 Be in good general health based on a physical examination, medical history, vital signs, 12-lead ECG and screening urine and blood tests Test negative for drugs of abuse other than cannabis, including breath alcohol at the screening visit and at clinic admission 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. Have a body mass index (BMI) in the range of 18 to 36 kg/m2 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 Have no allergies to any of the ingredients used to prepare vapor (THC, d-limonene). Report having experienced anxiety after consuming cannabis in the past. Exclusion Criteria: Non-medical use of psychoactive drugs other than, nicotine, alcohol, or caffeine 3 month prior to the Screening Visit; 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. 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. 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. Use of dronabinol (Marinol®) within the past month. Average use of cannabis more than 2 times per week in the prior 3 months. History of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina). Abnormal EKG result that in the investigator's opinion is clinically significant. Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing. Having previously sought medical attention to manage adverse effects following acute cannabis use. Individuals with anemia or who have donated blood in the prior 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (5mL distilled water) | Drug: Placebo<br>* Placebo vapor (distilled water)<br>|
| Experimental: Vaporized low THC<br>15mg of pure THC | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: Vaporized high THC<br>30mg of pure THC | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: Vaporized low d-limonene<br>1mg of d-limonene | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: Vaporized high d-limonene<br>5mg of d-limonene | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: Low THC and low d-limonene<br>15mg of THC paired with 1mg of d-limonene | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: High THC and low d-limonene<br>30mg of THC paired with 1mg of d-limonene | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: Low THC and high d-limonene<br>15mg of THC paired with 5mg of d-limonene | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: High THC and high d-limonene<br>30mg of THC paired with 5mg of d-limonene | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|
| Experimental: High THC and 15mg d-limonene<br>30mg of THC paired with 15mg of d-limonene | Drug: Vaporized THC, limonene, or THC and limonene<br>* Acute drug exposure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 0-6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 0-6 hours | 
| 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. | 0-6 hours | 
| Mean Peak Change From Baseline Heart Rate | Peak change from baseline in Heart Rate (bpm) measured in seated position by automated monitor | 0-6 hours |