Cannabis and Alcohol for Impairment

Overseen By Tory Spindle, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive drugs

Disqualifiers: Significant medical condition, Psychiatric condition, Severe alcohol use disorder, others

Compensation: Varies

Number of Visits: 9

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This human laboratory study will use cognitive, behavioral, and subjective measures to characterize impairment associated with co-use of alcohol and vaporized cannabis. Participants (n=32) will complete 7 double-blind, double-dummy outpatient sessions in randomized order. In each session, participants will self-administer placebo (0 mg THC) or active vaporized cannabis (5 or 25 mg THC, via a handheld vaporizer called the Mighty Medic) and a placebo drink (BAC 0.0%) or alcohol drink calculated to produce a breath alcohol concentration (BAC) of 0.05%. Participants will also complete a positive control session in which the participant administers placebo cannabis and alcohol at a target BAC of 0.08% (the legal threshold for driving impairment in most U.S. states).

Will I have to stop taking my current medications?

The trial requires that participants do not use certain prescription medications that may interact with the study drugs. If you are taking medications like warfarin, cyclosporine, or amphotericin B, you may need to stop them to participate.

What data supports the effectiveness of the drug combination of cannabis and alcohol for impairment?

Research indicates that combining cannabis and alcohol can lead to greater impairment than using either drug alone, particularly affecting skills necessary for driving. This suggests that the combination has a significant impact on psychomotor performance, which is the ability to perform tasks that require both mental and physical activity. ^{1 2 3 4 5}

Is it safe to use cannabis and alcohol together?

Using cannabis and alcohol together can impair driving and other skills more than using either one alone, increasing the risk of accidents. While alcohol is a known risk factor for injury, the effects of cannabis are less clear, with some studies showing impairment and others suggesting a protective effect. It's important to be cautious and avoid combining these substances, especially if planning to drive. ^{1 3 5 6 7}

How does the drug combination of vaporized cannabis and alcohol differ from other treatments for impairment?

This treatment is unique because it involves the combination of vaporized cannabis and low-dose alcohol, which may produce synergistic effects that are different from using either substance alone. The method of administration (vaporization) and the combination of these two substances are not standard treatments for impairment, making this approach novel. ^{2 3 5 8 9}

Research Team

Tory Spindle, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for individuals who can safely consume alcohol and cannabis. Participants will be tested on how these substances, alone or together, affect their thinking, behavior, and feelings. They must be able to attend multiple sessions and have no health conditions that would make the study unsafe for them.

Inclusion Criteria

Report at least 1 lifetime instance of simultaneous alcohol and cannabis use

I have not donated blood in the last 30 days.

Have provided written informed consent

Exclusion Criteria

Meet criteria for severe alcohol use disorder (MINI for DSM-V)

Psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in the past month

CIWA-Ar score > 9

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Experimental Sessions

Participants complete 7 double-blind, double-dummy outpatient sessions with various combinations of vaporized cannabis and alcohol

7 sessions over 4-5 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the experimental sessions

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Alcohol
• Vaporized Cannabis

Trial Overview The study tests the effects of vaporized cannabis (with THC levels of either 0 mg as a placebo, 5 mg or 25 mg), combined with alcoholic or non-alcoholic drinks designed to reach specific blood alcohol concentrations. Each participant will try different combinations in a controlled setting over several visits.

Participant Groups

Group I: Placebo cannabis + low dose alcohol Experimental Treatment 2 Interventions

Participants administer vaporized cannabis containing 0mg THC in combination with an alcohol drink (0.05 percent BAC).

Group II: Placebo cannabis + high dose alcohol Experimental Treatment 2 Interventions

Participants administer vaporized cannabis containing 0mg THC in combination with an alcohol drink (0.08 percent BAC).

Group III: Low dose cannabis with placebo alcohol Experimental Treatment 2 Interventions

Participants administer vaporized cannabis containing 5mg THC in combination with a placebo alcohol drink.

Group IV: Low dose cannabis with low dose alcohol Experimental Treatment 2 Interventions

Participants administer vaporized cannabis containing 5mg THC in combination with an alcohol drink (0.05 percent BAC).

Group V: High dose cannabis with placebo alcohol Experimental Treatment 2 Interventions

Participants administer vaporized cannabis containing 25mg THC in combination with a placebo alcohol drink.

Group VI: High dose cannabis with low dose alcohol Experimental Treatment 2 Interventions

Participants administer vaporized cannabis containing 25mg THC in combination with an alcohol drink (0.05 percent BAC).

Group VII: Placebo cannabis + placebo alcohol Placebo Group 2 Interventions

Participants administer vaporized cannabis containing 0mg THC in combination with a placebo alcohol drink.

Alcohol is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Ethanol for:

• None (not approved as a therapeutic agent)

Approved in European Union as Ethanol for:

• None (not approved as a therapeutic agent)

Approved in Canada as Ethanol for:

• None (not approved as a therapeutic agent)

Approved in Japan as Ethanol for:

• None (not approved as a therapeutic agent)

Approved in China as Ethanol for:

• None (not approved as a therapeutic agent)

Approved in Switzerland as Ethanol for:

• None (not approved as a therapeutic agent)

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

In a study of injured drivers presenting to emergency departments in cannabis-legal states, 8% reported cannabis use within 8 hours before a motor vehicle collision (MVC), but biosample testing revealed a higher prevalence of 18%.

High-risk crash features were prevalent among drivers using cannabis, whether alone or with alcohol; however, seriously injured patients were less likely to report cannabis use compared to alcohol use, indicating potential differences in the impact of these substances on crash severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis presentations to the emergency department after MVC in the era of legalization for recreational use. Choo, EK., Nishijima, D., Trent, S., et al.[2022]

Vaporizing cannabis significantly increases blood levels of THC and its active metabolite 11-OH-THC, especially when combined with low-dose alcohol, which may lead to greater impairment in driving performance.

In a study of 32 adult cannabis smokers, those who consumed alcohol before vaporizing cannabis showed higher maximum blood concentrations of THC, suggesting that the combination of these substances could enhance impairment and should be carefully considered in driving-related regulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol. Hartman, RL., Brown, TL., Milavetz, G., et al.[2019]

In a study involving 11 healthy volunteers, very low doses of ethanol and THC were tested in combination, but the results showed no evidence of synergistic effects on cognitive performance or subjective responses.

The combined effects of these substances were not stronger than their individual effects, and in some cases, they were even less effective when taken together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers. Ballard, ME., de Wit, H.[2021]

The study found that combining ethanol and marihuana significantly worsened psychomotor performance, particularly skills needed for driving, indicating an additive or synergistic effect on impairment.

Interestingly, taking ethanol before smoking marihuana did not significantly affect subjective feelings of intoxication, heart rate, or THC levels in the blood, suggesting that the combination primarily impacts performance rather than subjective experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between marihuana and ethanol: effects on psychomotor performance. Perez-Reyes, M., Hicks, RE., Bumberry, J., et al.[2019]

Cannabis and alcohol both impair driving skills, but cannabis effects vary more between individuals due to factors like tolerance and smoking technique, while alcohol consistently increases crash risk.

Combining cannabis with alcohol significantly worsens driving impairment compared to using either substance alone, highlighting the need for caution and advising cannabis users to wait several hours before driving.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of cannabis compared with alcohol on driving. Sewell, RA., Poling, J., Sofuoglu, M.[2022]

This study will assess the effects of both oral and vaporized cannabis on driving performance, cognitive abilities, and field sobriety in healthy adults, involving 64 participants across two double-blind, placebo-controlled trials.

By examining the impact of cannabis alone and in combination with alcohol, the research aims to enhance understanding of impairment levels, which could influence public policy and law enforcement standards regarding cannabis and alcohol use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of oral and vaporized cannabis alone, and in combination with alcohol, on driving performance using the STISIM driving simulator: A two-part, double-blind, double-dummy, placebo-controlled, randomized crossover clinical laboratory protocol. Zamarripa, CA., Novak, MD., Weerts, EM., et al.[2023]

Alcohol use significantly increases the risk of injury, with a relative risk of 3.00 for those who consumed alcohol within six hours prior to injury, indicating a strong dose-response relationship.

Interestingly, cannabis use was associated with a lower risk of injury (relative risk of 0.33), suggesting a potential protective effect, although this finding should be interpreted cautiously due to the small number of cannabis users in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alcohol and cannabis use as risk factors for injury--a case-crossover analysis in a Swiss hospital emergency department. Gmel, G., Kuendig, H., Rehm, J., et al.[2022]

In a study with alcohol-preferring rats, combining ethanol and THC significantly impaired memory in an object recognition task, highlighting the risks of co-abusing these substances.

The memory impairment was linked to the activation of CB1 receptors, as a specific antagonist reversed the effects of THC, indicating a potential mechanism for the observed synergistic action between ethanol and THC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory impairment following combined exposure to delta(9)-tetrahydrocannabinol and ethanol in rats. Ciccocioppo, R., Antonelli, L., Biondini, M., et al.[2019]

Research indicates that the co-use of cannabis and alcohol among adolescents may have mixed effects, with some studies suggesting potential protective benefits for neuropsychological outcomes compared to alcohol-only use, while others link co-use to negative consequences like poorer academic performance and impaired driving.

The current understanding of how cannabis and alcohol affect adolescent brain development and behavior is complicated and inconsistent, highlighting the need for more comprehensive research to guide effective prevention and intervention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring Cannabis and Alcohol Co-Use in Adolescents: A Narrative Review of the Evidence. Karoly, HC., Ross, JM., Ellingson, JM., et al.[2021]

References

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

Cannabis presentations to the emergency department after MVC in the era of legalization for recreational use. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Controlled Cannabis Vaporizer Administration: Blood and Plasma Cannabinoids with and without Alcohol. [2019]

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

Combined effects of acute, very-low-dose ethanol and delta(9)-tetrahydrocannabinol in healthy human volunteers. [2021]

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

Interaction between marihuana and ethanol: effects on psychomotor performance. [2019]

5. England pubmed.ncbi.nlm.nih.gov

The effect of cannabis compared with alcohol on driving. [2022]

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

The effects of oral and vaporized cannabis alone, and in combination with alcohol, on driving performance using the STISIM driving simulator: A two-part, double-blind, double-dummy, placebo-controlled, randomized crossover clinical laboratory protocol. [2023]

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

Alcohol and cannabis use as risk factors for injury--a case-crossover analysis in a Swiss hospital emergency department. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Memory impairment following combined exposure to delta(9)-tetrahydrocannabinol and ethanol in rats. [2019]

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

Exploring Cannabis and Alcohol Co-Use in Adolescents: A Narrative Review of the Evidence. [2021]