THC Testing for Cannabis Impairment

(NHTSA-II Trial)

Overseen By Diana King, B.A

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Disqualifiers: Pregnancy, Cancer, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

32 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot participate if you have a serious medical condition or if you test positive for drugs or alcohol (except THC) on the test day.

What data supports the effectiveness of the drug Medium THC for cannabis impairment?

The study on marijuana smoking showed that higher THC content and more puffs led to increased THC levels in the blood, which correlated with impaired performance on tasks. This suggests that Medium THC could effectively indicate impairment by affecting performance similarly. ^{1 2 3 4 5}

Is THC generally safe for human use?

THC, the main active ingredient in cannabis, can cause side effects like increased heart rate, low blood pressure when standing up, lung irritation if smoked, and issues with movement and thinking. People with heart, lung, or mental health problems should be cautious, and monitoring is important during use. ^{6 7 8 9 10}

How does the drug Medium THC differ from other treatments for cannabis impairment?

Medium THC is unique because it focuses on measuring the psychoactive component of cannabis, THC, to assess impairment, which is not a standard approach for treating cannabis impairment. This method is novel as it aims to provide an objective measure of cannabis use levels, potentially improving the accuracy of impairment assessments. ^{8 11 12 13 14}

What is the purpose of this trial?

This research responds to NHTSA's request with a proposal to increase our understanding of smoked cannabis' (CNB's) acute effects on driving-relevant cognition and simulated driving performance, the persistence of these deficits over the hours after use, and the influence of prior experience with CNB on these effects. This extension study will aim to further investigate marijuana impaired behavior, using a similar design to our previous NHTSA Examine the Feasibility of a Standardized Field Test for Marijuana Impairment and the prior NIDA Neuroscience of Marijuana-Impaired Driving award, that used similar techniques and measures to quantify marijuana impaired automobile driving. We will be utilizing tasks and assessments that were shown to be strong indicators for cognitive and driving impairment in our NHTSA study.

Research Team

Godfrey Pearlson, M.D

Principal Investigator

Yale University

Eligibility Criteria

This trial is for people aged 18-55 with a driver's license and at least 2 years of driving experience. Participants should be English speakers who have used cannabis recently and felt its effects. Excluded are those with adverse reactions to cannabis, low IQ, new users, drug or alcohol use on test day (except THC), pregnant or breastfeeding women, individuals unable to understand study instructions, former users abstaining from cannabis, anyone with significant head trauma or medical conditions affecting cognition.

Inclusion Criteria

Able and willing to provide written informed consent, and willing to commit to the study protocol

I have a driver's license and over 2 years of driving experience.

Able to read, speak, and understand English

Exclusion Criteria

My high blood pressure is not under control.

I have had a head injury that made me unconscious for more than 30 minutes or caused a concussion for 30 days.

Positive screen for drug and alcohol (except THC) on test day will result in rescheduling the appointment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Dose Visit

Participants receive placebo and high THC marijuana doses, followed by cognitive and driving tests

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after dosing

1 day

1 visit (in-person)

Treatment Details

Interventions

• Medium THC
• Placebo THC

Trial Overview The study tests the effects of smoked marijuana on tasks related to driving skills and cognitive functions over time after use. It compares medium THC levels against a placebo in participants with prior marijuana experience. The goal is to better understand how recent use impairs behavior relevant to driving.

Participant Groups

Group I: Placebo Marijuana Experimental Treatment 1 Intervention

Placebo Marijuana will be administered.

Group II: Medium THC Marijuana Experimental Treatment 1 Intervention

Medium THC marijuana will be administered.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Highway Traffic Safety Administration (NHTSA)

Collaborator

Trials

8

Recruited

940+

Hartford Hospital

Collaborator

Trials

140

Recruited

19,700+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

A daily dose of 40 mg of rimonabant for 15 days effectively reduced the physiological effects of smoked cannabis, such as tachycardia, similar to a single higher dose of 90 mg on the first day of treatment.

While the 40 mg dose significantly decreased subjective effects of cannabis on day 8, it did not maintain this effect by day 15, indicating that repeated dosing may not consistently reduce the subjective experience of cannabis effects over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Huestis, MA., Boyd, SJ., Heishman, SJ., et al.[2019]

A meta-analysis of 10 randomized controlled trials involving 2,027 participants found that behavioral therapies (BTs) significantly improve outcomes for cannabis use disorders compared to control conditions, with an effect size of 0.44, indicating that patients receiving BTs fared better than 66% of those in control groups.

Behavioral therapies were effective in reducing both the frequency and severity of cannabis use, as well as improving psychosocial functioning, with larger effect sizes observed in studies using waitlist controls compared to those with active control comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral therapies for treatment-seeking cannabis users: a meta-analysis of randomized controlled trials. Davis, ML., Powers, MB., Handelsman, P., et al.[2022]

Clinical studies on cannabis administration are essential for understanding its effects and developing treatments for cannabis dependence, with different methods of administration (smoking, oral, intravenous) each having unique safety and efficacy profiles.

Acute adverse effects from cannabis can include tachycardia, cognitive impairment, and anxiety, necessitating careful screening and monitoring of participants to ensure safety during research studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methods for clinical research involving cannabis administration. Gorelick, DA., Heishman, SJ.[2019]

The safety of cannabis and cannabinoid medications is a significant concern, and while some safety information can be drawn from recreational use studies, medical and recreational users may experience different effects.

There is a pressing need for long-term safety monitoring of cannabinoid use in patients, as clinical experience is still developing, which will help inform both therapeutic decisions and public policy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues concerning the medical use of cannabis and cannabinoids. Ware, MA., Tawfik, VL.[2019]

This paper introduces a framework for assessing the safety of additives in cannabis concentrates, aimed at helping regulators and manufacturers without extensive toxicological expertise.

Based on data from over 54,000 users of smart vaporization devices, the study suggests a standard consumption assumption of 100 mg per day for cannabis concentrates to facilitate risk assessments of these additives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A First-Tier Framework for Assessing Toxicological Risk from Vaporized Cannabis Concentrates. Vreeke, S., Faulkner, DM., Strongin, RM., et al.[2022]

A standardized dose of CannEpil, a medicinal cannabis oil, did not significantly impair overall driving performance but did lead to increased variability in speed and weaving during a simulated drive, particularly noticeable between 20 and 30 minutes after administration.

Changes in eye behavior, such as increased fixation duration and altered blink patterns, suggest that eye tracking could be a useful tool for assessing cannabis-related driver impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of CannEpil® on simulated driving performance and co-monitoring of ocular activity: A randomised controlled trial. Manning, B., Hayley, AC., Catchlove, S., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

A comprehensive breath test that confirms recent use of inhaled cannabis within the impairment window. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Marijuana smoking: effect of varying delta 9-tetrahydrocannabinol content and number of puffs. [2013]

3. Germany pubmed.ncbi.nlm.nih.gov

Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Screening for cannabis use disorder among young adults: Sensitivity, specificity, and item-level performance of the Cannabis Use Disorders Identification Test - Revised. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Behavioral therapies for treatment-seeking cannabis users: a meta-analysis of randomized controlled trials. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Methods for clinical research involving cannabis administration. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Examining impairment and kinetic patterns associated with recent use of hemp-derived Δ8-tetrahydrocannabinol: case studies. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Disposable screen printed sensor for the electrochemical detection of delta-9-tetrahydrocannabinol in undiluted saliva. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Safety issues concerning the medical use of cannabis and cannabinoids. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A First-Tier Framework for Assessing Toxicological Risk from Vaporized Cannabis Concentrates. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Objective Identification of Cannabis Use Levels in Clinical Populations Is Critical for Detecting Pharmacological Outcomes. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Determination of delta 9-tetrahydrocannabinol in human blood and saliva by high-performance liquid chromatography with amperometric detection. [2019]

13. Ireland pubmed.ncbi.nlm.nih.gov

Screening for cannabinoids in blood using EMIT: concentrations of delta-9-tetrahydrocannabinol in relation to EMIT results. [2019]

14. United States pubmed.ncbi.nlm.nih.gov

Effect of CannEpil® on simulated driving performance and co-monitoring of ocular activity: A randomised controlled trial. [2023]