Cannabis and Tobacco for DUI

(CASE-CT Trial)

Overseen By Patricia Di Ciano

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must not be taking: Psychoactive drugs

Disqualifiers: Substance use disorder, Nicotine dependence, Schizophrenia, others

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

Compensation: Varies

Number of Visits: 4

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to stop using psychoactive medications or drugs. If you are taking medications for a medical condition, you may continue them, but you must abstain from alcohol and other non-essential drugs for 48 hours before the study session.

What data supports the effectiveness of the drug Cannabis and Tobacco for DUI?

Research suggests that targeting both cannabis and tobacco use together may improve outcomes for quitting either or both substances. Additionally, cannabinoids have shown potential benefits in other medical conditions, such as pain relief and appetite stimulation. ^{1 2 3 4 5}

Is cannabis and tobacco use generally safe for humans?

Cannabis and its components, like THC and CBD, can have side effects such as sedation, sleep disturbances, and potential interactions with other medications. Cannabis use is linked to adverse cardiovascular and pulmonary effects, and it may impair driving skills, increasing the risk of motor vehicle accidents. ^{6 7 8 9 10}

How does the drug Cannabis and Tobacco differ from other treatments for DUI?

This drug is unique because it involves the use of cannabis and tobacco together, which may affect impairment differently than other substances. The combination of THC (the main psychoactive component of cannabis) and CBD (another component of cannabis) with tobacco could influence the level of impairment and the body's processing of these substances, potentially offering a novel approach to understanding DUI cases. ^{1 2 11 12 13}

What is the purpose of this trial?

Co-administration of cannabis and tobacco is a common practice, but there is little experimental evidence aimed at understanding the reasons for this prevalence. Some preliminary evidence suggests that tobacco may actually counteract the cognitive-impairing effects of cannabis, and may also increase the subjective ('liking') effects of cannabis, but results are inconclusive. Further, there are no studies into the effects of tobacco on other cannabis-related harms such as driving, or on the ability of tobacco to alter the blood levels of THC, the chemical responsible for the psychoactive properties of cannabis. The purpose of the present study will be to evaluate the effects of tobacco, cannabis or combinations of tobacco and cannabis on driving, cognition, subjective effects and blood THC. Driving will be assessed using a state-of-the-art driving simulator that allows for the safe and objective measurement of the effects of intoxicating substances on driving. Participants will be regular users of cannabis and will be invited to the lab for four counterbalanced test sessions. In these test sessions they will drive the simulator and undergo cognitive tests before and after smoking: 1) cannabis; 2) tobacco; 3) cannabis + tobacco; or 4) placebo. Outcomes will be measured at several time points after smoking the product. Participants will also give blood for determination of levels of THC, and will complete subjective effects questionnaires both before and after smoking the cigarette. This study will be one of the first experimental laboratory studies of the reasons behind co-administration of tobacco and cannabis.

Eligibility Criteria

This trial is for adults aged 19-45 who smoke or vape cannabis occasionally (1 to 4 times a week) and have used tobacco. They must have a normal heart rate, blood pressure, ECG, and be willing to avoid alcohol and other drugs before the sessions. Participants need experience with smoked cannabis in the past year, at least 100 lifetime cigarettes smoked, recent nicotine use, and a valid driver's license.

Inclusion Criteria

I have had a G2 or full G driver's license for over a year.

Provides written and informed consent

Use of any nicotine (smoked, vaped, etc) in the past year

Exclusion Criteria

Pregnancy or breastfeeding

I use medications that affect my mood or the way I think.

Current alcohol or other substance use disorder, including cannabis (as assessed with the SCID)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Test Sessions

Participants undergo four counterbalanced test sessions involving driving simulation and cognitive tests before and after smoking different combinations of cannabis and tobacco.

4 sessions

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the test sessions, including assessments of mood, cognition, and THC levels.

4-5 hours post each session

Treatment Details

Interventions

• Cannabis
• Combined and Separate Effects of Cannabis and Tobacco: Psychomotor, Subjective and Physiological Outcomes
• Placebo
• Tobacco

Trial Overview The study investigates how smoking cannabis alone or with tobacco affects driving skills using a simulator, cognition, subjective feelings of 'liking', and THC levels in blood. Participants will attend four test sessions where they'll smoke: only cannabis; only tobacco; both; or placebo.

Participant Groups

Group I: Tobacco and cannabis Experimental Treatment 1 Intervention

A cigarette with active cannabis and active tobacco

Group II: Tobacco Experimental Treatment 1 Intervention

A cigarette with placebo cannabis and active tobacco

Group III: Placebo Experimental Treatment 1 Intervention

A cigarette containing placebo cannabis and placebo tobacco

Group IV: Cannabis Experimental Treatment 1 Intervention

A cigarette with active cannabis and placebo tobacco

Cannabis is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Cannabis for:

• Chronic pain
• Nausea and vomiting associated with chemotherapy
• Spasticity associated with multiple sclerosis

Approved in United States as Cannabis for:

• Seizures associated with Lennox-Gastaut syndrome and Dravet syndrome
• Nausea and vomiting associated with chemotherapy

Approved in European Union as Cannabis for:

• Spasticity associated with multiple sclerosis
• Chronic pain

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Findings from Research

Integrating a tobacco intervention with treatment for cannabis use disorders (CUD) was feasible for 32 participants over 12 weeks, showing that it can positively impact tobacco use without harming cannabis abstinence outcomes.

Participants achieved an average of 3.6 consecutive weeks of cannabis abstinence, similar to a historical control group, and over half initiated tobacco quit attempts, indicating that targeting both substances may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes from a computer-assisted intervention simultaneously targeting cannabis and tobacco use. Lee, DC., Budney, AJ., Brunette, MF., et al.[2022]

In a study of 6,134 cannabis users in Norway, 76% of those with THC in their blood also had CBD, indicating that many users consume cannabis with both cannabinoids present.

While higher concentrations of both THC and CBD were linked to impairment in a clinical test, only THC levels were significantly associated with impairment, suggesting that CBD does not mitigate THC's effects on driving ability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

THC and CBD in blood samples and seizures in Norway: Does CBD affect THC-induced impairment in apprehended subjects? Havig, SM., Høiseth, G., Strand, MC., et al.[2018]

Reducing the number of days individuals use cannabis is linked to improvements in their overall functioning, suggesting that this could be a valuable outcome measure in treatment trials for cannabis use disorder (CUD).

While reductions in the amount of cannabis used showed inconsistent links to functional improvements, biologically-confirmed reductions in usage frequency may serve as a reliable endpoint for future clinical trials, highlighting the need for further research on quantifying cannabis reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring Within-Individual Cannabis Reduction in Clinical Trials: A Review of the Methodological Challenges. Tomko, RL., Gray, KM., Huestis, MA., et al.[2022]

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 72 controlled clinical trials indicates that cannabinoids have significant therapeutic potential for various conditions, including as antiemetics, appetite stimulants, and analgesics.

Cannabinoids may be beneficial in treating debilitating diseases such as cancer and AIDS, as well as neurological disorders like multiple sclerosis and epilepsy, highlighting their diverse applications in medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. Ben Amar, M.[2022]

A significant portion of cannabis products (58.5%) lacked information on CBD content, and most products (72-100%) with CBD fell into the highly intoxicating THC:CBD ratio category (≥1:1), suggesting that patients may experience enhanced acute effects and intoxication.

Medical and recreational cannabis products are largely similar, posing a risk for patients seeking therapeutic benefits, as they may inadvertently consume high-potency products that lead to unwanted side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potency and Therapeutic THC and CBD Ratios: U.S. Cannabis Markets Overshoot. Pennypacker, SD., Cunnane, K., Cash, MC., et al.[2022]

Nearly 50% of CBD users experienced adverse drug events (ADEs), with common issues including elevated liver enzymes, sedation, and sleep disturbances, indicating a significant safety concern.

CBD has a high potential for drug-drug interactions (DDIs) due to its effects on drug metabolism, particularly with enzymes like CYP3A4 and CYP2C19, suggesting that careful monitoring and dose adjustments may be necessary for patients on multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. Brown, JD., Winterstein, AG.[2020]

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]

Cannabis use is increasing due to decriminalization and legalization, but its adverse effects, including cardiovascular and pulmonary issues, as well as links to malignancy and neuropsychiatric disorders, are becoming more evident despite limited research.

The rise in cannabis use among minors has led to more cases of overdose and toxicity, highlighting concerns about its safety, particularly regarding impaired driving and motor vehicle accidents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Impact of Cannabis on Human Health. Chandy, M., Nishiga, M., Wei, TT., et al.[2023]

Laboratory studies indicate that marijuana can significantly impair driving abilities, but real-world studies have produced mixed results regarding its impact on crash risk, suggesting a need for better data analysis.

The study highlights that the Fatality Analysis Reporting System (FARS) has limitations that can lead to biased conclusions about drugged driving, recommending it should not be used for precise risk estimates but may be useful under specific conditions for comparing drug-related crash risks to alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marijuana and the Risk of Fatal Car Crashes: What Can We Learn from FARS and NRS Data? Romano, E., Torres-Saavedra, P., Voas, RB., et al.[2018]

Both tobacco and marijuana smoking activate the cytochrome P450 (CYP) 1A2 enzyme, which can lead to increased metabolism of certain drugs, necessitating dose adjustments after smoking cessation to avoid toxicity.

Δ9-tetrahydrocannabinol (Δ9THC) and cannabidiol (CBD) are primarily metabolized by the CYP3A4 enzyme, indicating that interactions with other drugs affecting CYP3A4 could significantly alter their effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. Anderson, GD., Chan, LN.[2023]

A study of 531 confiscated cannabis samples established classification thresholds for THC-rich and CBD-rich cannabis, helping to differentiate between products based on their THC and CBD content.

Despite CBD-cannabis being legal and generally not resulting in positive drug tests, trace amounts of THC can still elevate blood THC levels above legal driving limits, posing potential legal risks for consumers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoid concentrations in confiscated cannabis samples and in whole blood and urine after smoking CBD-rich cannabis as a "tobacco substitute". Hädener, M., Gelmi, TJ., Martin-Fabritius, M., et al.[2021]

Cannabidiol (CBD), a significant component of Cannabis sativa, is believed to have potential medical benefits, including anti-convulsant and anti-psychotic properties, but remains unapproved by the FDA for medical use, classifying it as a Schedule I drug.

Two e-cigarette products claiming to contain CBD were found to have higher concentrations than labeled, raising concerns about the regulation, quality control, and safety of these unregulated products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes. Peace, MR., Butler, KE., Wolf, CE., et al.[2020]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Outcomes from a computer-assisted intervention simultaneously targeting cannabis and tobacco use. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

THC and CBD in blood samples and seizures in Norway: Does CBD affect THC-induced impairment in apprehended subjects? [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Measuring Within-Individual Cannabis Reduction in Clinical Trials: A Review of the Methodological Challenges. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

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

5. Ireland pubmed.ncbi.nlm.nih.gov

Cannabinoids in medicine: A review of their therapeutic potential. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Potency and Therapeutic THC and CBD Ratios: U.S. Cannabis Markets Overshoot. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use. [2020]

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

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

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

Adverse Impact of Cannabis on Human Health. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Marijuana and the Risk of Fatal Car Crashes: What Can We Learn from FARS and NRS Data? [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Drug Interactions with Tobacco, Cannabinoids and Smoking Cessation Products. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

Cannabinoid concentrations in confiscated cannabis samples and in whole blood and urine after smoking CBD-rich cannabis as a "tobacco substitute". [2021]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Two Commercially Available Cannabidiol Formulations for Use in Electronic Cigarettes. [2020]