Behavioral Pharmacology of Cannabis and Nicotine

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04124432

Enrollment

Registered

2019-10-11

Start date

2020-09-15

Completion date

2023-08-31

Last updated

2024-04-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cannabis, Nicotine

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.

Interventions

DRUGCannabis

Cannabis will be smoked

DRUGNicotine

Nicotine will be smoked or vaporized

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Outcomes Assessor)

Masking description

placebo controlled, double-blind

Intervention model description

All participants will complete all dose conditions (study arms) in a randomized order

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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).
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 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 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 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 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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Cannabis With and Without Nicotine This was a within-subjects, cross-over design in which all participants were exposed to all 7 conditions in a randomized order.	20
Total	20

Baseline characteristics

Characteristic	Cannabis With and Without Nicotine
Age, Continuous	33.47 Years STANDARD_DEVIATION 8.53
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Black or African American	6 Participants
Race (NIH/OMB) More than one race	0 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	12 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
deaths Total, all-cause mortality	0 / 23	0 / 20	0 / 24	0 / 22	0 / 21	0 / 22	0 / 21
other Total, other adverse events	0 / 23	0 / 20	1 / 24	0 / 22	1 / 21	0 / 22	0 / 21
serious Total, serious adverse events	0 / 23	0 / 20	0 / 24	0 / 22	0 / 21	0 / 22	0 / 21

Outcome results

Primary

Amount of Nicotine (mL of Smoke/Vapor) Inhaled

Amount of nicotine used (determined by total volume (mL) of cigarette smoke or JUUL vapor inhaled) after cannabis exposure in each session.

Time frame: 0-5 hours