The Impact and Detection of Driving Impairments Associated With Acute Cannabis Smoking

NCT02849587 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 160641
• Study Type: interventional
• Target: 199
• Locations: 1 country
• Sites: 1

Brief Summary

This study was authorized by the California Legislature (Assembly Bill 266, the Medical Marijuana Regulation and Safety Act to help with detection of driving under the influence of cannabis. One hundred and eighty healthy volunteers will inhale smoked cannabis with either 0% (placebo), 5.9%, or 13.4% Δ9-tetrahydrocannabinol (THC) at the beginning of the day, and then complete driving simulations, iPad-based performance assessments, and bodily fluid draws (e.g., blood, saliva, breath) before the cannabis smoking and a number of times over the subsequent 6 hours after cannabis smoking. The purpose is to determine (1) the relationship of the dose of Δ9-THC on driving performance and (2) the duration of driving impairment in terms of hours from initial use, (3) if saliva or expired air can serve as a useful substitute for blood sampling of Δ9-THC, and (4) if testing using an iPad can serve as a useful adjunct to the standardized field sobriety test in identifying acute impairment from cannabis.

Conditions

Cannabis Intoxication

Keywords

Driving Under the Influence; Memory Impairment; Reaction Time; Time Perception; Cannabis; Marijuana; Whole Blood; Oral Fluid; Breath; Driving simulator

Outcome Measures

Primary Outcomes (1)

• Change in Composite Drive Score (CDS) From Pre-smoking Simulation

  The Composite Drive Score (CDS) is a z-score comprised of key variables from the simulator tasks (SDLP, speed deviation, and task accuracy during the modified Surrogate Reference Task (mSuRT); coherence from the car following task). This outcome reflects the change in CDS from the pre-smoking assessment, at each timepoint. The z-score indicates the number of standard deviations away from the mean from the baseline performance for the entire group (n = 191). A Z-score of 0 is equal to the mean of a reference population (in this case the pre-smoking performance for the entire group). Higher z-scores at each timepoint indicate worse performance (variables that went in the opposite direction were reflected in order to have all variables have the same direction). When examining the change in Composite Drive Score (this outcome variable), a higher score indicates a decline in performance (e.g., Time 2 minus Time 1).

  Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking

Secondary Outcomes (13)

• Simulator: Standard Deviation of Lateral Position (SDLP)

  Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking

• Simulator: Speed Deviation

  Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking

• Simulator: Correct Hits on mSuRT

  Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking

• Simulator: Car Following - Coherence

  Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking

• Simulator: Response Delay - Car Following

  Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking

Study Arms (3)

Placebo Cannabis

PLACEBO COMPARATOR

Subjects will smoke cannabis with placebo THC (.02%) ad libitum

Drug: Cannabis

Cannabis with 5.9% THC

EXPERIMENTAL

Subjects will smoke cannabis cigarettes with 5.9% THC ad libitum

Drug: Cannabis

Cannabis with 13.4% THC

EXPERIMENTAL

Subjects will smoke cannabis cigarettes with 13.4% THC ad libitum

Drug: Cannabis

Interventions

Cannabis DRUG

Participants will smoke a cannabis cigarette ad libitum as per their usual routine

Also known as: Marijuana

Cannabis with 13.4% THC; Cannabis with 5.9% THC; Placebo Cannabis

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be a licensed driver.
• Need to have acuity of 20/40 or better, with or without correction on a Snellen Visual Acuity eye chart.

You may not qualify if:

• At the discretion of the examining physician, individuals with significant cardiovascular, hepatic or renal disease, uncontrolled hypertension, and chronic pulmonary disease (eg, asthma, COPD) will be excluded.
• Unwillingness to abstain from cannabis for 2 days prior to screening and experimental visits
• Positive pregnancy test
• A positive result on toxicity screening for cocaine, amphetamines, opiates, and phencyclidine (PCP) will exclude individuals from participation.
• Unwilling to refrain from driving or operating heavy machinery for four hours after consuming study medication.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

Center for Medicinal Cannabis Research, UC San Diego

San Diego, California, 92103, United States

Location

Related Publications (12)

• Hartman RL, Huestis MA. Cannabis effects on driving skills. Clin Chem. 2013 Mar;59(3):478-92. doi: 10.1373/clinchem.2012.194381. Epub 2012 Dec 7.

  PMID: 23220273 BACKGROUND

• Papafotiou K, Carter JD, Stough C. An evaluation of the sensitivity of the Standardised Field Sobriety Tests (SFSTs) to detect impairment due to marijuana intoxication. Psychopharmacology (Berl). 2005 Jun;180(1):107-14. doi: 10.1007/s00213-004-2119-9. Epub 2004 Dec 24.

  PMID: 15619106 BACKGROUND

• Fabritius M, Chtioui H, Battistella G, Annoni JM, Dao K, Favrat B, Fornari E, Lauer E, Maeder P, Giroud C. Comparison of cannabinoid concentrations in oral fluid and whole blood between occasional and regular cannabis smokers prior to and after smoking a cannabis joint. Anal Bioanal Chem. 2013 Dec;405(30):9791-803. doi: 10.1007/s00216-013-7412-1. Epub 2013 Nov 8.

  PMID: 24202191 BACKGROUND

• Beck O, Stephanson N, Sandqvist S, Franck J. Detection of drugs of abuse in exhaled breath from users following recovery from intoxication. J Anal Toxicol. 2012 Nov-Dec;36(9):638-46. doi: 10.1093/jat/bks079. Epub 2012 Oct 7.

  PMID: 23045289 BACKGROUND

• Marcotte TD, Heaton RK, Wolfson T, Taylor MJ, Alhassoon O, Arfaa K, Ellis RJ, Grant I. The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group. J Int Neuropsychol Soc. 1999 Nov;5(7):579-92. doi: 10.1017/s1355617799577011.

  PMID: 10645701 BACKGROUND

• Marcotte TD, Rosenthal TJ, Roberts E, Lampinen S, Scott JC, Allen RW, Corey-Bloom J. The contribution of cognition and spasticity to driving performance in multiple sclerosis. Arch Phys Med Rehabil. 2008 Sep;89(9):1753-8. doi: 10.1016/j.apmr.2007.12.049.

  PMID: 18760160 BACKGROUND

• Hubbard JA, Hoffman MA, Ellis SE, Sobolesky PM, Smith BE, Suhandynata RT, Sones EG, Sanford SK, Umlauf A, Huestis MA, Grelotti DJ, Grant I, Marcotte TD, Fitzgerald RL. Biomarkers of Recent Cannabis Use in Blood, Oral Fluid and Breath. J Anal Toxicol. 2021 Sep 17;45(8):820-828. doi: 10.1093/jat/bkab080.

  PMID: 34185831 RESULT

• Hoffman MA, Hubbard JA, Sobolesky PM, Smith BE, Suhandynata RT, Sanford S, Sones EG, Ellis S, Umlauf A, Huestis MA, Grelotti DJ, Grant I, Marcotte TD, Fitzgerald RL. Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers. J Anal Toxicol. 2021 Sep 17;45(8):851-862. doi: 10.1093/jat/bkab078.

  PMID: 34173005 RESULT

• Hubbard JA, Smith BE, Sobolesky PM, Kim S, Hoffman MA, Stone J, Huestis MA, Grelotti DJ, Grant I, Marcotte TD, Fitzgerald RL. Validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect cannabinoids in whole blood and breath. Clin Chem Lab Med. 2020 Apr 28;58(5):673-681. doi: 10.1515/cclm-2019-0600.

  PMID: 31527291 RESULT

• Sobolesky PM, Smith BE, Hubbard JA, Stone J, Marcotte TD, Grelotti DJ, Grant I, Fitzgerald RL. Validation of a liquid chromatography-tandem mass spectrometry method for analyzing cannabinoids in oral fluid. Clin Chim Acta. 2019 Apr;491:30-38. doi: 10.1016/j.cca.2019.01.002. Epub 2019 Jan 4.

  PMID: 30615854 RESULT

• Marcotte TD, Umlauf A, Grelotti DJ, Sones EG, Mastropietro KF, Suhandynata RT, Huestis MA, Grant I, Fitzgerald RL. Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis: A Randomized Clinical Trial. JAMA Psychiatry. 2023 Sep 1;80(9):914-923. doi: 10.1001/jamapsychiatry.2023.2345.

  PMID: 37531115 DERIVED

• Marcotte TD, Umlauf A, Grelotti DJ, Sones EG, Sobolesky PM, Smith BE, Hoffman MA, Hubbard JA, Severson J, Huestis MA, Grant I, Fitzgerald RL. Driving Performance and Cannabis Users' Perception of Safety: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Mar 1;79(3):201-209. doi: 10.1001/jamapsychiatry.2021.4037.

  PMID: 35080588 DERIVED

Related Links

• Center for Medicinal Cannabis Research, UC San Diego

MeSH Terms

Conditions

Driving Under the Influence; Memory Disorders; Marijuana Abuse

Interventions

nabiximols

Condition Hierarchy (Ancestors)

Criminal Behavior; Behavior; Dangerous Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Thomas D. Marcotte, Phd
• Organization: University of California, San Diego; Center for Medicinal Cannabis Research

tmarcotte@ucsd.edu

619-543-5044

Study Officials

• Thomas D Marcotte, PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Product will be dispensed from the Research Pharmacy. All assessors, investigators, and participants are blinded to the THC content.
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants will be randomized to smoke a cannabis cigarette containing placebo (.02%), 5.9% or 13.4% THC.

Study Record Dates

• First Submitted: July 14, 2016
• First Posted: July 29, 2016
• Study Start: February 24, 2017
• Primary Completion: June 17, 2019
• Study Completion: June 17, 2019
• Last Updated: January 4, 2022
• Results First Posted: January 4, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon manuscript publications
• Access Criteria: Approved researchers

Locations

US (1)