Vaping THC From Electronic Cigarettes

NCT02955329 | Completed Phase 3 Results FDA Drug FDA Device

• 2 other identifiers: 18-248543R01DA039264-02S1
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to understand THC pharmacology and the safety of cannabis vaping, including the pharmacology and safety of co-administration of nicotine and THC. The study is designed as a within-subjects single-blinded crossover study. Fourteen smokers of tobacco cigarettes and cannabis will switch between three conditions, namely: (a) vaping cannabis leaf, (b) vaping tobacco containing nicotine and (c) vaping a combination of cannabis leaf and tobacco containing nicotine. All participants will vape each product with the PAX loose-leaf vaporizer. The study will be conducted during three outpatient visits separated by at least 48 hours. The order of treatment (cannabis leaf, tobacco with nicotine, cannabis leaf \& tobacco with nicotine) will be counterbalanced between subjects. Subjects will be blinded to the content of the vaporizer on the study day but will be told during screening that they will vape cannabis alone, tobacco alone, and cannabis plus tobacco with nicotine.

Conditions

Marijuana Dependence

Keywords

THC; Tobacco; Vaping

Outcome Measures

Primary Outcomes (11)

• Mean Delivered and Retained Doses

  Delivered Tetrahydrocannabinol (THC) and nicotine doses are estimated as the change in e-cigarette weight × concentration of THC or nicotine in e-liquid. The amount of THC or nicotine systemically retained is estimated as delivered dose minus amount in gas traps.

  Study Day 1-3

• Median Peak THC Concentration (Cmax)

  Median peak concentration of THC between vaped loose-leaf cannabis, mixture of cannabis and tobacco containing nicotine, and the tobacco alone treatment condition will be reported

  Study Day 1-3

• Median Peak Nicotine Concentration (Cmax)

  Median peak concentration of nicotine between vaped loose-leaf cannabis, mixture of cannabis and tobacco containing nicotine, and the tobacco alone treatment condition will be reported

  Study Day 1-3

• Median THC Exposure

  Median exposure of nicotine using area under the blood/plasma concentration-time curve(AUC) between vaped loose-leaf cannabis, mixture of cannabis and tobacco containing nicotine, and the tobacco alone treatment condition will be reported

  Study Day 1-3

• Median Nicotine Exposure

  Compare median exposure of nicotine using AUC (area under the blood/plasma concentration-time curve) between vaped loose-leaf tobacco containing nicotine vs. mixture of cannabis and tobacco containing nicotine.

  Study Day 1-3

• Mean Heart Rate

  Heart rate monitoring by pulse oximeter

  Study Day 1-3

• Mean Score on the Drug Effects Questionnaire (DEQ)

  The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances which assessed the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance by instructing participants to place a mark on a 100mm vertical, visual, analog scale with scores ranging from 0 ="not at all" to 100 = "extremely" for each question. The mean of the individual responses is used to general a total score with a range from 0 to 100, with higher scores indicate a greater "liking" of the effects of the substance. The mean and standard deviation of each treatment condition will be reported.

  Study Day 1-3

• Mean Scores on the Marijuana Craving Questionnaire-Short Form (MCQ-SF)

  This 12-item multidimensional measure assesses cannabis craving based on 4 factors: Compulsivity, Emotionality, Expectancy, Purposefulness. Each item asks about the respondent's feelings and thoughts about smoking marijuana as he or she is completing the questionnaire (i.e., right now). Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree) with higher scores indicating a greater level of craving. The calculation of each subscale is as follows: Compulsivity: Mean of items 2, 7, and 10; Emotionality: Mean of items 4, 6, and 9; Expectancy: Mean of items 5, 11, and 12; Purposefulness: Mean of items 1, 3, and 8 with the minimum possible score = 1 and the maximum possible score = 7 for any subscale. The mean and standard deviation of each subscale for each treatment condition will be reported.

  Study Day 1-3

• Mean Scores on the Modified Cigarette Evaluation Questionnaire (mCEQ)

  The modified Cigarette Evaluation Questionnaire (mCEQ) uses three multi-item subscales and two single items: "Smoking Satisfaction" (items 1, 2, and 12);"Psychological Reward" (items 4 through 8); "Aversion" (items 9 and 10);"Enjoyment of Respiratory Tract Sensations" (item 3); and "Craving Reduction"(item 11). Scores for each subscale are calculated as the mean of the individual item responses or the single item. Higher scores indicate greater intensity on that scale. Items are rated on a seven-point scale ranging from 1 (not at all) to 7 (extremely) and total scores are averaged across all items with a minimum average score of 1 and a maximum average score of 7. Higher scores indicate greater intensity of each smoking effect with, for example, greater satisfaction or psychological reward after smoking. The mean and standard deviation for each treatment condition will be reported.

  Study Day 1-3

• Mean Scores on the Positive Affect Negative Affect Schedule (PANAS)

  The Positive and Negative Affect Schedule (PANAS) is a brief scale is comprised of 20 items, with 10 items measuring positive affect (e.g., excited, inspired) and 10 items measuring negative affect (e.g., upset, afraid). Each item is rated on a five-point Likert Scale, ranging from 1 = Very Slightly or Not at all to 5 = Extremely, to measure the extent to which the affect has been experienced in a specified time frame and the final score is derived out of the sum of the ten items on both the positive and negative side. Scores can range from 10-50 for both the Positive and Negative Affect with the lower scores representing lower levels of Positive/Negative Affect and higher scores representing higher levels of Positive/Negative Affect.

  Study Day 1-3

• Mean Scores on the Minnesota Nicotine Withdrawal Scale (MNWS)

  The Minnesota Nicotine Withdrawal Scale is an 7-item self - report scale designed to measure the severity of craving and withdrawal symptoms experienced during smoking cessation. Each item is rated on a scale of 0 to 4 with 0=none,1= Slight, 2= Mild, 3= Moderate, and 4=Severe. Seven of the items are symptoms derived from the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Tobacco Withdrawal diagnosis and are as follows: depression, insomnia, irritability/frustration/anger, anxiety/nervousness, difficulty concentrating, restlessness, increased appetite and at least five of seven items must have responses in order to generate a reliable score. The responses to each item are summed to produce a total withdrawal summary score with greater scores indicating a higher level of severity in nicotine withdrawal symptoms overall. The mean and standard deviation of each treatment condition will be reported with a minimum mean score of 0 and a maximum mean score of 4.

  Study Day 1-3

Study Arms (3)

Tobacco Arm

EXPERIMENTAL

Participants will vape tobacco leaves with nicotine out of the PAX device.

Drug: Nicotine; Device: PAX Loose Leaf Vaporizer

Cannabis Arm

EXPERIMENTAL

Participants will vape marijuana leaves with THC (Tetrahydrocannabinol) out of the PAX device.

Drug: Cannabis; Device: PAX Loose Leaf Vaporizer

Combined Cannabis and Tobacco Arm

EXPERIMENTAL

Participants will vape flavorless 6% nicotine e-liquid, followed by THC (Tetrahydrocannabinol) out of the PAX device.

Drug: Nicotine; Drug: Cannabis; Device: PAX Loose Leaf Vaporizer

Interventions

Nicotine DRUG

Participants will vape tobacco leaves with nicotine out of the PAX device.

Also known as: Tobacco Leaf

Combined Cannabis and Tobacco Arm; Tobacco Arm

Cannabis DRUG

Participants will vape marijuana leaves with nicotine out of the PAX device.

Also known as: Marijuana Leaf

Cannabis Arm; Combined Cannabis and Tobacco Arm

PAX Loose Leaf Vaporizer DEVICE

In all three arms, the participant will be using the same PAX electronic cigarette device. The only difference is whether the participant will be vaping nicotine only, THC only, or nicotine and THC.

Cannabis Arm; Combined Cannabis and Tobacco Arm; Tobacco Arm

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>=21 years \<=70 years
• Regular user of tobacco cigarettes (daily or most days)
• Regular user of cannabis in any form (combusted or ingested) at least 5 days out of the month.
• Positive for Tetrahydrocannabinol (THC) on screening toxicology test
• Willing to abstain from tobacco smoking and all other combustible products (ex: cigars) for 12 hours prior to each outpatient hospital admission.
• Willing to abstain from smoking/ingesting cannabis for 12 hours prior to each outpatient hospital admission.
• Willing to abstain from using any kind of nicotine products for 12 hours prior to each outpatient hospital admission (ex: electronic cigarettes, nicotine replacement therapy).
• Saliva cotinine ≥ 30 ng/mL and/or NicAlert of 6
• Healthy (based on limited physical examination and medical history collected during screening)
• Heart rate \< 105 beats per minute (BPM)
• Systolic Blood Pressure \< 160 and \> 90 (considered out of range if both machine and manual readings are above/below these thresholds)
• Diastolic Blood Pressure \< 100 and \> 50 (considered out of range if both machine and manual readings are above/below these thresholds)
• Body Mass Index ≤\<=38.0

You may not qualify if:

• Medical (The following unstable medical conditions):
• Heart disease
• Uncontrolled hypertension
• Thyroid disease (okay if controlled with medication)
• Diabetes
• Hepatitis B or C or Liver disease
• Glaucoma
• Prostatic hypertrophy
• History of paranoia after marijuana use
• Psychiatric conditions
• Current or past schizophrenia, and/or current or past bipolar disorder
• Adult onset Attention-deficit/hyperactivity disorder (ADHD) (if being treated)
• Drug/Alcohol Dependence
• Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program and are currently abstaining from drug and alcohol
• Positive toxicology test at the screening visit (THC \& prescribed medications okay)

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Zuckerberg San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Related Publications (9)

• King BA, Patel R, Nguyen KH, Dube SR. Trends in awareness and use of electronic cigarettes among US adults, 2010-2013. Nicotine Tob Res. 2015 Feb;17(2):219-27. doi: 10.1093/ntr/ntu191. Epub 2014 Sep 19.

  PMID: 25239961 BACKGROUND

• Arrazola RA, Singh T, Corey CG, Husten CG, Neff LJ, Apelberg BJ, Bunnell RE, Choiniere CJ, King BA, Cox S, McAfee T, Caraballo RS; Centers for Disease Control and Prevention (CDC). Tobacco use among middle and high school students - United States, 2011-2014. MMWR Morb Mortal Wkly Rep. 2015 Apr 17;64(14):381-5.

  PMID: 25879896 BACKGROUND

• St Helen G, Havel C, Dempsey DA, Jacob P 3rd, Benowitz NL. Nicotine delivery, retention and pharmacokinetics from various electronic cigarettes. Addiction. 2016 Mar;111(3):535-44. doi: 10.1111/add.13183. Epub 2015 Nov 11.

  PMID: 26430813 BACKGROUND

• St Helen G, Ross KC, Dempsey DA, Havel CM, Jacob P 3rd, Benowitz NL. Nicotine Delivery and Vaping Behavior During ad Libitum E-cigarette Access. Tob Regul Sci. 2016 Oct;2(4):363-376. doi: 10.18001/TRS.2.4.8.

  PMID: 28393086 BACKGROUND

• Center for Behavioral Health Statistics and Quality. Behavioral health trends in the United States: Results from the 2014 National Survey on Drug Use and Health. NSDUH; 2015.

  BACKGROUND

• Schauer GL, King BA, Bunnell RE, Promoff G, McAfee TA. Toking, Vaping, and Eating for Health or Fun: Marijuana Use Patterns in Adults, U.S., 2014. Am J Prev Med. 2016 Jan;50(1):1-8. doi: 10.1016/j.amepre.2015.05.027. Epub 2015 Aug 12.

  PMID: 26277652 BACKGROUND

• Morean ME, Kong G, Camenga DR, Cavallo DA, Krishnan-Sarin S. High School Students' Use of Electronic Cigarettes to Vaporize Cannabis. Pediatrics. 2015 Oct;136(4):611-6. doi: 10.1542/peds.2015-1727. Epub 2015 Sep 7.

  PMID: 26347431 BACKGROUND

• Akre C, Michaud PA, Berchtold A, Suris JC. Cannabis and tobacco use: where are the boundaries? A qualitative study on cannabis consumption modes among adolescents. Health Educ Res. 2010 Feb;25(1):74-82. doi: 10.1093/her/cyp027. Epub 2009 Jun 10.

  PMID: 19515745 BACKGROUND

• Amos A, Wiltshire S, Bostock Y, Haw S, McNeill A. 'You can't go without a fag...you need it for your hash'--a qualitative exploration of smoking, cannabis and young people. Addiction. 2004 Jan;99(1):77-81. doi: 10.1111/j.1360-0443.2004.00531.x.

  PMID: 14678065 BACKGROUND

MeSH Terms

Conditions

Marijuana Abuse; Vaping

Interventions

Nicotine; Tobacco Products; nabiximols

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Smoking; Behavior

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Dr. Gideon St. Helen
• Organization: University of California, San Francisco

gideon.sthelen@ucsf.edu

628-206-2687

Study Officials

• Neal L Benowitz, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2016
• First Posted: November 4, 2016
• Study Start: March 20, 2019
• Primary Completion: November 30, 2019
• Study Completion: November 30, 2019
• Last Updated: June 29, 2023
• Results First Posted: April 30, 2021

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)