Marijuana + Opioid Interaction for Substance Use Disorders

Overseen By Paul Nuzzo

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Shanna Babalonis, PhD

Disqualifiers: Significant medical complications, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the interaction between marijuana and opioids when used together, particularly how they might alter usage patterns. Researchers aim to understand how marijuana affects opioid use and vice versa, using varying doses of each drug. The trial includes two main groups: one receiving either marijuana or a placebo, and the other receiving either an opioid or a placebo, with participants unaware of which they receive. Individuals experienced in using both substances and able to stay at the University of Kentucky Hospital for about 6.5 weeks may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

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

Research has shown that both marijuana and opioids present safety concerns. Although many people consider marijuana low risk, it can still cause problems such as relationship issues and reduced success at work. Some individuals may also overuse it and develop a disorder.

Opioids, however, are known to be addictive and can lead to serious issues, including overdose. In 2017, more than 72,000 Americans died from drug overdoses, including those involving opioids, highlighting the need for caution with opioid use.

The study is in its early stages, so researchers are still learning about the safety of using both substances together. This phase typically involves a small number of participants to ensure no major risks before proceeding to further testing. Participants should consider these factors when deciding whether to join the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are exploring the combination of marijuana and opioids for treating substance use disorders because these treatments offer a fresh approach compared to traditional methods. Unlike standard treatments, which often involve opioid antagonists or behavioral therapies, this trial examines how marijuana might interact with opioids to potentially reduce dependency. The unique delivery methods, such as vaporized marijuana and intranasal opioids, provide new ways to administer these substances, which might enhance effectiveness or reduce side effects. By investigating these interactions, researchers hope to uncover novel ways to manage substance use disorders with potentially fewer risks and improved outcomes.

What evidence suggests that this trial's treatments could be effective for substance use disorders?

Research suggests that cannabis might help people with cannabis use disorder, but its effectiveness for other substance use disorders, such as opioid use disorder, remains unclear. About 10% of cannabis users may become addicted. For opioids, medications like buprenorphine and methadone can reduce overdose risk and the need for emergency care in individuals with opioid use disorder. However, strong evidence does not support the long-term use of opioids for chronic pain. This trial will explore how marijuana and opioids might influence each other's use. Participants will be assigned to either a double-blind marijuana/placebo administration arm or a double-blind opioid/placebo administration arm. Limited data exist on the effectiveness of these treatments when used together. ^{5 6 7 8 9}

Who Is on the Research Team?

Shanna Babalonis, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for adults aged 18-50 who have used marijuana and opioids before, are generally healthy, and can stay at the University of Kentucky Hospital research unit for about 6.5 weeks with meals provided. People with significant medical conditions cannot participate.

Inclusion Criteria

General good health

Experience with marijuana and opioids

Willing to live at the University of Kentucky Hospital (research unit) for approx. 6.5 weeks (meals are provided)

Exclusion Criteria

Significant medical complications/conditions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive double-blind administration of intranasal opioid agonist/placebo and vaporized marijuana/placebo to examine drug self-administration

8 weeks

Multiple sessions for drug administration and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Marijuana
• Opioid

Trial Overview

The study is looking into how marijuana affects the use of oxycodone (a type of opioid) and vice versa. Participants will be given different doses of each drug in a controlled environment to see how one influences the desire or effects of the other.

How Is the Trial Designed?

Group I: Double-blind opioid/placebo administration Experimental Treatment 2 Interventions

Participants will receive double-blind administration of intranasal opioid agonist/placebo

Group II: Double-blind marijuana/placebo administration Experimental Treatment 2 Interventions

Participants will receive double-blind administration of vaporized marijuana/placebo

Marijuana is already approved in United States for the following indications:

Approved in United States as Cannabis for:

• Nausea and vomiting caused by chemotherapy
• Loss of appetite and weight loss associated with HIV/AIDS
• Seizures and epilepsy (specifically Lennox-Gastaut syndrome and Dravet syndrome)

Approved in United States as Epidiolex for:

• Seizures and epilepsy (specifically Lennox-Gastaut syndrome and Dravet syndrome)

Approved in United States as Dronabinol (Marinol, Syndros) for:

• Nausea and vomiting caused by chemotherapy
• Loss of appetite and weight loss associated with HIV/AIDS

Approved in United States as Nabilone (Cesamet) for:

• Nausea and vomiting caused by chemotherapy

Who Is Running the Clinical Trial?

Shanna Babalonis, PhD

Lead Sponsor

Trials

5

Recruited

140+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Among older adults aged 50 and above, past-year marijuana use is significantly associated with a higher likelihood of nonmedical opioid dependence and use, with an adjusted odds ratio of 9.6 for opioid dependence and 6.4 for nonmedical opioid use.

The study found that illicit heroin was the most commonly misused opioid among marijuana users, highlighting a concerning trend that policymakers and healthcare providers should consider when addressing opioid misuse in older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marijuana users are likely to report opioid misuse among adults over 50 years in representative sample of the United States (2002-2014). Ramadan, MM., Banta, JE., Bahjri, K., et al.[2021]

In a study analyzing approximately 800,000 urine drug tests from pain management patients, the presence of THC-COOH, a marker for marijuana use, was linked to significantly lower levels of various opioids in urine samples.

This suggests that marijuana use may modulate opioid levels, potentially indicating a relationship where marijuana users have reduced opioid concentrations compared to non-users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced urinary opioid levels from pain management patients associated with marijuana use. Goggin, MM., Shahriar, BJ., Stead, A., et al.[2020]

Only 30% of patients with a new cannabis use disorder (CUD) diagnosis initiated treatment, and just 2.1% both initiated and engaged in treatment, indicating a significant gap in care for individuals with CUD.

Patients diagnosed in addiction treatment settings had the highest rates of treatment initiation (25%) and engagement (40.9%), suggesting that the setting of diagnosis plays a crucial role in treatment uptake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prevalence of Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement in treatment among patients with cannabis use disorders in 7 US health systems. Lapham, GT., Campbell, CI., Yarborough, BJH., et al.[2020]

In a study involving 152 opioid-dependent youth aged 15-21, cannabis use did not predict the level of opioid use during a 12-week treatment period, indicating that cannabis may not negatively impact opioid treatment outcomes.

Despite the prevalence of cannabis use among participants, with 50.3% reporting occasional use, the analysis found no significant association between cannabis use and opioid use levels, suggesting that cannabis use may not be a barrier to successful opioid treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of cannabis use with opioid outcomes among opioid-dependent youth. Hill, KP., Bennett, HE., Griffin, ML., et al.[2022]

In a study of 107 individuals undergoing treatment for opioid dependence, 66% were current marijuana users, and most continued using marijuana during treatment, indicating a high prevalence of co-use.

Marijuana use did not negatively impact treatment outcomes for opioid dependence, suggesting that patients may progress in their recovery without needing to abstain from marijuana.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marijuana use and treatment outcome among opioid-dependent patients. Budney, AJ., Bickel, WK., Amass, L.[2019]

In a long-term study of 615 individuals with heroin dependence, increased cannabis use after 24 months was linked to increased heroin use at 36 months, suggesting a potential risk factor for opioid use.

Conversely, higher heroin use at earlier time points was associated with decreased cannabis use later, indicating that the relationship between cannabis and heroin use is complex and not consistently bidirectional.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS). Wilson, J., Mills, KL., Sunderland, M., et al.[2023]

A review of 41 studies on cannabis use during medication-based treatment for opioid use disorder (MOUD) found that most studies showed no significant impact of cannabis on treatment outcomes like opioid use, adherence, or retention.

While some studies suggested potential benefits or harms of cannabis use, particularly in relation to cravings and withdrawal, overall, cannabis use does not appear to independently threaten the effectiveness of MOUD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relationship between cannabis use and patient outcomes in medication-based treatment of opioid use disorder: A systematic review. Lake, S., St Pierre, M.[2021]

THC, the main active ingredient in cannabis, can interact with other medications due to its metabolism by enzymes like CYP3A4 and CYP2C9, which may lead to adverse drug events, especially in patients with complex medical conditions.

Starting THC at low doses and carefully monitoring for interactions is recommended, as many drug-drug interactions can be unavoidable and may limit the effectiveness of THC-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug-Drug Interactions. Brown, JD.[2021]

Among 234,181 patients with drug use disorders, those with co-occurring opioid use disorder (OUD) and cannabis use disorder (CUD) had fewer opioid prescriptions compared to those with OUD only, suggesting a potential role of cannabis in reducing opioid use.

However, this group also faced higher risks of inpatient psychiatric admissions and homelessness, indicating that while cannabis may reduce opioid prescriptions, it does not necessarily lead to better overall outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Consequences of Co-Occurring Opioid Use Disorder and Cannabis Use Disorder Compared to Opioid Use Disorder Only. De Aquino, JP., Sofuoglu, M., Stefanovics, E., et al.[2022]

A systematic review and meta-analysis of six studies involving over 102,000 participants found that cannabis users are 2.76 times more likely to start using opioids compared to non-cannabis users.

Additionally, those with prior cannabis use are 2.52 times more likely to develop opioid use disorders, abuse, or dependence, although the overall evidence quality was low and should be interpreted cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weeding out the truth: a systematic review and meta-analysis on the transition from cannabis use to opioid use and opioid use disorders, abuse or dependence. Wilson, J., Mills, K., Freeman, TP., et al.[2023]

A study of 1,490 cannabinoid poisoning cases in Kentucky revealed that a significant portion (31.21%) involved other psychoactive substances, leading to increased hospital admissions and complications.

17.72% of patients experienced cardiac complications, highlighting the potential health risks associated with cannabinoid use, especially when combined with other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoid Poisoning-Related Emergency Department Visits and Inpatient Hospitalizations in Kentucky, 2017 to 2019. Britch, SC., Walsh, SL., Vickers-Smith, R., et al.[2023]

Cannabis can interact with important liver enzymes and transporters that affect the metabolism of various medications, particularly anticoagulants and antiplatelet agents, which are often prescribed to patients with heart conditions.

Specifically, cannabis may inhibit the metabolism of warfarin and clopidogrel, potentially leading to increased bleeding risk and reduced effectiveness of these medications, highlighting the need for caution in patients using cannabis alongside these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Cannabis and Interactions With Anticoagulant and Antiplatelet Agents. Greger, J., Bates, V., Mechtler, L., et al.[2021]

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