Behavioral Pharmacology of Cannabis and Nicotine

Phase 1

Completed

Conditions: Cannabis
Nicotine

Interventions: Drug: Cannabis
Drug: Nicotine

Registration Number: NCT04124432

Lead Sponsor: Johns Hopkins University

Brief Summary: This study will evaluate the individual and interactive pharmacokinetic and pharmacodynamic effects of smoked cannabis and nicotine.

Detailed Description: The proposed study will be conducted at the Johns Hopkins Behavioral Pharmacology Research Unit (BPRU). All participants will be healthy adult volunteers who are regular nicotine/tobacco users, and have prior experience with cannabis use. Participants will complete seven outpatient experimental test sessions (completed in a randomized order), under double-blind conditions in which participants will first self-administer smoked cannabis (either active or placebo), followed by nicotine (via a tobacco cigarette or an e-cigarette); there will also be one condition in which participants smoke active cannabis alone (without subsequent nicotine use). Nicotine self-administration will occur in an ad libitum fashion for 5 hours. Nicotine products will be the individual participant's preferred brand of cigarettes or the commercial pod-style e-cigarette the JUUL (pods will contain either 3% or 5% nicotine pods). Active cannabis will contain 10 mg tetrahydrocannabinol (THC) while placebo will contain 0 mg THC. During the ad libitum nicotine/tobacco-use period, various puffing behaviors (e.g., puff volume, puff duration, puff number, inter-puff-interval) will be measured using specialized equipment. Acute subjective effects of cannabis/nicotine, cannabis/nicotine withdrawal symptoms, craving, vital signs, and cognitive/psychomotor performance will also be assessed throughout the experimental sessions.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 26

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, and screening urine and blood tests
Test negative for drugs of abuse aside from cannabis (via urine sample) and alcohol (via breath sample) at the screening visit and upon arrival for each experimental session.
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 not donated blood in the prior 30 days.
Report prior experience inhaling cannabis.
Report using cannabis at least 5 times in the past year.
Smoke ≥5 tobacco cigarettes per day on average in the past month.
Use an e-cigarette at least 15 of the past 30 days.
Have a breath carbon monoxide (CO) of >8ppm or urine cotinine >200ng/mL to confirm current nicotine use status.

Exclusion Criteria

Non-medical use of psychoactive drugs (aside from cannabis) other than, nicotine, alcohol, or caffeine in the month prior to the Screening Visit;
History of or current evidence of significant medical or psychiatric illness which, in the opinion of the investigator or sponsor, will interfere with the study results or the safety of the subject.
Use of an over-the-counter (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 results 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 results or the safety of the subject.
History of clinically significant cardiac arrhythmias or vasospastic disease (e.g., Prinzmetal's angina).
Enrolled in another clinical trial or have received any drug as part of a research study within 30 days prior to dosing.
Epilepsy or a history of seizures.
Individuals who have a recent history of traumatic brain injury diagnosed by CT/MRI and have current sequela from prior brain injury, as determined by the study physician
Individuals with anemia.
Prior history of allergic or serious adverse reaction to either cannabis or tobacco/nicotine.
Average use of cannabis more than 2 times per week in the prior 3 months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
placebo cannabis with own brand cigarettes	Nicotine	Smoked placebo cannabis + ad-libitum use of preferred brand cigarettes
Placebo cannabis with high nicotine e-cigarette	Nicotine	Smoked placebo cannabis + ad-libitum use of high nicotine content E-Cig (5% nicotine JUUL)
Active cannabis with own brand cigarettes	Nicotine	Smoked cannabis containing 10mg THC + ad-libitum use of preferred brand cigarettes
Active cannabis with low nicotine e-cigarette	Nicotine	Smoked cannabis containing 10mg THC + ad-libitum use of low nicotine content E-Cig (3% nicotine JUUL)
Active cannabis with high nicotine e-cigarette	Nicotine	Smoked cannabis containing 10mg THC + ad-libitum use of high nicotine content E-Cig (5% nicotine JUUL)
Placebo cannabis with low nicotine e-cigarette	Nicotine	Smoked placebo cannabis + ad-libitum use of low nicotine content E-Cig (3% nicotine JUUL)
Active cannabis with own brand cigarettes	Cannabis	Smoked cannabis containing 10mg THC + ad-libitum use of preferred brand cigarettes
Active cannabis without nicotine	Cannabis	Smoked cannabis containing 10mg THC + No nicotine/tobacco
Active cannabis with low nicotine e-cigarette	Cannabis	Smoked cannabis containing 10mg THC + ad-libitum use of low nicotine content E-Cig (3% nicotine JUUL)
placebo cannabis with own brand cigarettes	Cannabis	Smoked placebo cannabis + ad-libitum use of preferred brand cigarettes
Active cannabis with high nicotine e-cigarette	Cannabis	Smoked cannabis containing 10mg THC + ad-libitum use of high nicotine content E-Cig (5% nicotine JUUL)
Placebo cannabis with low nicotine e-cigarette	Cannabis	Smoked placebo cannabis + ad-libitum use of low nicotine content E-Cig (3% nicotine JUUL)
Placebo cannabis with high nicotine e-cigarette	Cannabis	Smoked placebo cannabis + ad-libitum use of high nicotine content E-Cig (5% nicotine JUUL)

Primary Outcome Measures

Name	Time	Method
Amount of Nicotine (mL of Smoke/Vapor) Inhaled	0-5 hours	Amount of nicotine used (determined by total volume (mL) of cigarette smoke or JUUL vapor inhaled) after cannabis exposure in each session.

Secondary Outcome Measures

Name	Time	Method
Mean Peak Change From Baseline Cannabis Craving as Assessed by the Cannabis Craving Questionnaire	0-5 hours	Mean peak change from baseline rating (0-100) of "Craving" with 0 being no craving and 100 being maximum craving
Mean Peak Change From Baseline Self-reported Drug Effect as Assessed by the Drug Effect Questionnaire (DEQ)	0-5 hours	Mean Peak Change From Baseline rating (0-100) of Drug Effect on the DEQ, with 0 being no effect and 100 being maximum effect.
Mean Peak Change From Baseline Working Memory Performance as Assessed by the Paced Auditory Serial Addition Task (PASAT)	0-5 hours	Computerized version of Paced Auditory Serial Addition Task will be administered to assess working memory performance. Total correct trials out of 90 recorded is primary outcome (higher scores indicate better performance).
Mean Peak Change From Baseline Behavioral Task Performance as Assessed by the DRUID App	0-5 hours	Behavioral task performance will be assessed with the DRUID app's Global impairment score (range 0-100), where lower scores indicate better performance.
Mean Peak Change From Baseline Tobacco Craving as Assessed by the Tobacco Craving Questionnaire	0-5 hours	Mean peak change from baseline rating (0-100) of "Craving" with 0 being no craving and 100 being maximum craving.
Mean Peak Change From Baseline Psychomotor Performance as Assessed by the Digit Symbol Substitution Task (DSST)	0-5 hours	Computerized version of Digit Symbol Substitution Task will be administered to assess psychomotor performance. Total correct trials in 90-seconds. Minimum score of 0 but no maximum score (higher scores indicate better performance).