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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how using alcohol and vaporized cannabis together affects cognitive and behavioral functions. Participants will try different combinations of cannabis and alcohol, including placebos (inactive substances), to measure how these substances impact impairment. This study could help inform safety guidelines for people who use both substances simultaneously. The trial seeks individuals who have experienced binge drinking at least once in the past three months and have used cannabis at least once in the past three years, along with a history of using both substances together.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking safety insights.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vaporized cannabis can have strong effects, especially at higher doses. Studies indicate that using cannabis with 25 mg of THC can lead to noticeable effects such as anxiety and memory problems. These effects tend to be stronger when vaping compared to smoking. At lower doses, vaping cannabis with 5 mg of THC is usually easier to handle, with fewer negative effects reported. People often experience shorter periods of impairment with lower THC doses.

This trial tests both high and low doses of cannabis. While high doses can cause more side effects, low doses are generally safer and cause fewer issues. However, since this trial is in an early phase, researchers are closely monitoring safety to understand how well participants tolerate the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore the combined effects of vaporized cannabis and alcohol on impairment. Unlike traditional impairment studies that might focus on substances separately, this study examines how different doses of THC, the active component in cannabis, interact with varying levels of alcohol. This approach could provide unique insights into real-world scenarios where both substances are used together, potentially leading to more informed guidelines on safety and consumption. Additionally, the use of vaporized cannabis offers a modern delivery method that might influence how quickly and intensely effects are felt, compared to other forms of cannabis consumption.

What evidence suggests that this trial's treatments could be effective for impairment?

This trial will explore the effects of different doses of vaporized cannabis and alcohol. Research has shown that high doses of vaporized cannabis, such as 25 mg of THC, can impair movement, reaction time, and decision-making, making activities like driving more dangerous. Studies have found that vaping these amounts has stronger effects than smoking, which might feel more intense for infrequent cannabis users.

In contrast, low doses of vaporized cannabis, such as 5 mg of THC, usually have little effect on thinking and decision-making. These effects are generally mild and dissipate within a couple of hours. Overall, low doses are well tolerated, and any negative effects are short-lived. Participants in this trial will be assigned to various treatment arms to assess these effects in combination with different alcohol doses or placebos. ^{3 6 7 8 9}

Who Is on the Research Team?

Tory Spindle, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. psychologytoday.com psychologytoday.com/us/blog/addiction-outlook/202412/the-many-risks-of-cannabis-and-high-dose-thc-use

The Many Risks of Cannabis and High-Dose THC Use THC impairs motor coordination, reaction time, and judgment, increasing risks for motor-vehicle and other accidents, and higher THC doses cause ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9361180/

Assessment of cognitive and psychomotor impairment ... Low oral/vaporized doses did not impair cognitive/psychomotor performance relative to placebo but produced positive subjective effects. High oral/vaporized ...

3. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2018/12/vaping-cannabis-produces-stronger-effects-than-smoking-cannabis-for-infrequent-users

Vaping Cannabis Produces Stronger Effects Than ... Those who vaped any dose of THC also reported higher levels of dry mouth and dry eyes than those who smoked it. For example, when vaping 25 ...

4. cannabisevidence.org cannabisevidence.org/clinician-resources/clinician-briefs/cannabis-and-cognition/

Cannabis and Cognition There is clear evidence that acute cannabis intoxication negatively impacts cognitive functioning in a variety of domains, especially learning, memory, and ...

5. samhsa.gov samhsa.gov/substance-use/learn/marijuana/risks

Know the Effects, Risks and Side Effects of Marijuana Research shows that people who use marijuana are more likely to have relationship problems, worse educational outcomes, lower career achievement, and reduced ...

6. samhsa.gov samhsa.gov/

Home | SAMHSA - Substance Abuse and Mental Health ... SAMHSA leads efforts to advance behavioral health across the U.S., offering resources for mental health, substance use, and community well-being.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6324384/

Acute Effects of Smoked and Vaporized Cannabis in Healthy ... Significant, sometimes adverse, drug effects can occur at relatively low THC doses in infrequent cannabis users, and accordingly these data ...

8. ncids.org ncids.org/2021/marijuana-impairment-faq/

Marijuana Impairment FAQ The main reasons for the disconnect between THC blood concentration and impairment is that impairment occurs in the brain, not the blood, and ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0953620521001527

“Is medical cannabis safe for my patients?” A practical ... We provide clear recommendations for patients being considered for cannabis (eg precautions, contraindications and drug interactions).