Dronabinol for Pain Management in Opioid Users

(THC Trial)

Overseen By Joao P. De Aquino, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must be taking: Methadone, Buprenorphine

Must not be taking: Cannabis, Opioids

Disqualifiers: Psychotic disorders, Neurological illness, others

Compensation: Varies

Number of Visits: 5

Duration: 3 sessions, each separated by at least 72 hours

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests dronabinol to determine if it can help manage pain for individuals with opioid use disorder who are on methadone or buprenorphine treatment. Researchers aim to discover whether dronabinol, a form of medical cannabis, can reduce pain sensitivity and improve mood and cognitive skills compared to a placebo. Individuals who have previously used cannabis, have opioid use disorder, and are stable on methadone or buprenorphine treatment might be suitable for this trial. As an Early Phase 1 trial, this research focuses on understanding how dronabinol works in people, offering participants a chance to contribute to groundbreaking knowledge.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications, but you must be on a stable dose of any psychoactive drugs that affect pain threshold or tolerance. If possible, take your morning dose after the study visit.

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

Research has shown that dronabinol, a substance from cannabis, has been studied for its safety in people. One study found that users of dronabinol experienced more minor side effects than non-users, but no major health problems were reported. This suggests that while mild side effects may occur, dronabinol is generally safe.

Another study examined the long-term use of dronabinol for pain relief and found it to be safe, with no signs of addiction or misuse. Participants did not develop dependency.

These findings suggest that dronabinol is relatively safe, particularly for managing pain, though it may cause mild side effects. It is important to consult a healthcare provider about any concerns before joining a study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Dronabinol is unique because it utilizes a cannabinoid, specifically a synthetic form of THC, to manage pain in opioid users. Unlike standard pain management treatments, which typically involve opioid medications that can risk dependency and other side effects, dronabinol offers a non-opioid alternative. Researchers are excited because dronabinol has the potential to alleviate pain by interacting with the body's endocannabinoid system, offering a different mechanism of action that might reduce reliance on opioids. Additionally, dronabinol's formulation in 2.5mg and 5mg doses allows for flexible dosing to tailor pain management to individual needs.

What evidence suggests that dronabinol could be an effective treatment for pain management in opioid users?

Research has shown that dronabinol, a substance found in cannabis, can help reduce pain. One study found that participants taking dronabinol reported less pain and more satisfaction compared to those taking a placebo, which contains no active medicine. This trial will compare different dosages of dronabinol (2.5mg and 5mg) to a placebo to evaluate its effectiveness in pain management for opioid users. Strong evidence also indicates that cannabis can effectively treat long-term pain in adults. Another study found that people using cannabis-based treatments experienced less pain and required fewer opioids, which are strong painkillers. Overall, these findings suggest that dronabinol may help manage pain, especially for those with ongoing pain conditions. ^{2 6 7 8 9}

Who Is on the Research Team?

Joao P. De Aquino, M.D.

Principal Investigator

VA healthcare System West Haven CT

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-70 with opioid use disorder (OUD) who are on stable methadone or buprenorphine treatment. Participants must not be pregnant, should use birth control, have recent cannabis exposure without a cannabis use disorder, and no major medical issues or other substance use disorders.

Inclusion Criteria

Cannabis use, with recent cannabis exposure confirmed by urine toxicology

I am currently receiving methadone or buprenorphine for opioid use disorder.

I can understand and sign the consent form in English.

Exclusion Criteria

My doctor says I'm taking medication that could affect how I feel pain.

Liver function tests (ALT or AST) greater than 3x normal

Serious medical or neurological illness or treatment for a medical disorder that could interfere with study participation as determined by principal investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive dronabinol (2.5 mg, 5 mg) or placebo prior to their daily methadone or buprenorphine dose, followed by laboratory testing of opioid-related outcomes.

3 sessions, each separated by at least 72 hours

3 visits (in-person)

Follow-up

Participants undergo urine toxicology testing and a safety evaluation one week after the last study medication dose.

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Dronabinol
• Placebo

Trial Overview The study tests the effects of Dronabinol versus placebo in patients maintained on opioids. It involves taking the study medication before their regular dose of methadone or buprenorphine and then undergoing pain sensitivity tests, attentional bias tasks, mood assessments, cognitive performance evaluations, and blood tests to measure cytokines.

How Is the Trial Designed?

Group I: Dronabinol 5mg Active Control 1 Intervention

Dronabinol 5mg

Group II: Dronabinol 2.5mg Active Control 1 Intervention

Dronabinol 2.5mg

Group III: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

US Department of Veterans Affairs

Collaborator

Trials

881

Recruited

502,000+

Published Research Related to This Trial

In a study of 2,112 adult patients with chronic pain, 92.5% reported improvement in their primary symptoms after using cannabis-based oral formulations, indicating high efficacy as an adjuvant treatment.

The majority of patients experienced minimal side effects, with 71.7% reporting none, and the most common mild side effects, such as somnolence and dizziness, tended to decrease over time, suggesting that these formulations are safe for chronic pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia. Moreno-Sanz, G., Madiedo, A., Hernandez, P., et al.[2022]

In a study involving 24 multiple sclerosis (MS) patients, dronabinol (delta-9-tetrahydrocannabinol) significantly reduced spontaneous pain intensity compared to a placebo, indicating its potential analgesic effect.

Although the reduction in pain was modest, the findings suggest that dronabinol could be a valuable option for managing central pain in MS patients, a condition that is often challenging to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis--secondary publication]. Svendsen, KB., Jensen, TS., Bach, FW.[2013]

In a study of 19 patients with refractory neuropathic pain, 75% of those who continued dronabinol treatment for over 3 months reported an improvement in their health, suggesting its potential efficacy as a pain management option.

However, 74% of patients experienced at least one adverse event, with six needing to discontinue treatment, highlighting the importance of careful monitoring and evaluation of the drug's safety and benefit-risk balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of dronabinol in the treatment of resistant neuropathic pain: Feedback from patients followed in a multidisciplinary pain center]. Richet, E., Ferret, L., Gaboriau, L., et al.[2023]

In a study of 674 patients with severe neuropathic pain, the oromucosal spray nabiximols (NBX) showed a 55.4% improvement in pain relief compared to a 40.5% improvement with oral dronabinol (DRO), indicating that NBX is more effective for this condition.

NBX also had a better safety profile, with significantly lower rates of treatment-related adverse events (21.1% for NBX vs. 35% for DRO) and fewer discontinuations due to side effects (5.9% for NBX vs. 14.8% for DRO), highlighting its tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Effectiveness and Tolerability of Nabiximols (THC:CBD) Oromucosal Spray versus Oral Dronabinol (THC) as Add-on Treatment for Severe Neuropathic Pain in Real-World Clinical Practice: Retrospective Analysis of the German Pain e-Registry. Ueberall, MA., Essner, U., Vila Silván, C., et al.[2022]

In a clinical trial involving 240 multiple sclerosis patients over 16 weeks, dronabinol reduced neuropathic pain intensity by 1.92 points, similar to the 1.81 points reduction seen with placebo, indicating no significant difference in pain relief between the two treatments.

Dronabinol was found to be a safe long-term treatment option, with a higher rate of adverse reactions compared to placebo (50% vs. 25.9%), but these reactions decreased to 26% during extended use, and there were no significant signs of drug abuse or dependency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. Schimrigk, S., Marziniak, M., Neubauer, C., et al.[2018]

In a meta-analysis of 16 trials, nabilone was associated with significantly higher rates of drowsiness, dizziness, and dry mouth compared to placebo, indicating a notable risk of these side effects.

Dronabinol also showed increased occurrences of dry mouth, dizziness, and headache compared to placebo, but the overall severity of adverse events was generally mild-to-moderate, suggesting that the benefits may outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. Bajtel, Á., Kiss, T., Tóth, B., et al.[2022]

Nabilone (Cesamet) has not been approved by the FDA for marketing, contrary to previous claims, while dronabinol (Marinol) is the synthetic cannabinoid that has received FDA approval.

Corrections were made regarding the authors' affiliation and inaccuracies in references from the original article, ensuring the integrity of the published information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erratum. [2010]

A systematic review of 18 randomized controlled trials found that cannabinoids, including smoked cannabis and extracts, significantly relieve chronic non-cancer pain, particularly in conditions like neuropathic pain, fibromyalgia, and rheumatoid arthritis.

Cannabinoids were generally safe, with no serious adverse effects reported, and most side effects were mild to moderate, indicating they could be a viable option for patients seeking pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Lynch, ME., Campbell, F.[2022]

In a study involving 30 patients on opioids for chronic pain, dronabinol (synthetic THC) was found to significantly reduce pain intensity and increase treatment satisfaction compared to a placebo, indicating its potential as an effective adjuvant treatment.

The extended Phase II trial showed that titrated doses of dronabinol provided significant pain relief and reduced pain bothersomeness, although side effects were dose-related, suggesting careful monitoring is needed when using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. Narang, S., Gibson, D., Wasan, AD., et al.[2013]

In a study of 1,145 patients with refractory chronic pain, adding Δ9-tetrahydrocannabinol (dronabinol) to their treatment significantly reduced average pain intensity from 46.3 to 26.8 mm on a visual analog scale over 12 weeks.

Dronabinol was well tolerated, with 46.8% of patients reporting mild drug-related adverse events, and many patients were able to reduce or stop other pain medications during the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Tolerability of Dronabinol Use in Patients with Chronic Pain: A Retrospective Analysis of 12-Week Open-Label Real-World Data Provided by the German Pain e-Registry. Ueberall, MA., Horlemann, J., Schuermann, N., et al.[2022]

In a 12-week trial involving 156 cannabis-dependent adults, dronabinol (a synthetic form of THC) did not significantly increase the rate of abstinence compared to placebo, with both groups showing similar reductions in marijuana use.

However, dronabinol improved treatment retention (77% vs. 61% for placebo) and resulted in fewer withdrawal symptoms, suggesting it may be a well-tolerated option for supporting individuals in cannabis dependence treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Levin, FR., Mariani, JJ., Brooks, DJ., et al.[2022]

In a Phase II study with 29 healthy adults, the combination of hydromorphone and a low dose of dronabinol (2.5 mg) modestly improved pain relief, while higher doses of dronabinol (5 mg and 10 mg) increased the risk of abuse and adverse effects.

The study found that the effects of the drug combinations varied based on individual opioid sensitivity, suggesting that some people may respond differently to these treatments, which highlights the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Within-subject, double-blinded, randomized, and placebo-controlled evaluation of the combined effects of the cannabinoid dronabinol and the opioid hydromorphone in a human laboratory pain model. Dunn, KE., Bergeria, CL., Huhn, AS., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1526590007009674

Efficacy of Dronabinol as an Adjuvant Treatment for ... Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK425767/

Therapeutic Effects of Cannabis and Cannabinoids - NCBI - NIH CONCLUSION 4-1 There is substantial evidence that cannabis is an effective treatment for chronic pain in adults. Go to: CANCER. Cancer is a broad term used to ...

3. canada.ca canada.ca/en/health-canada/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids.html

For health care professionals: Cannabis and cannabinoids The two primary outcomes of the study, pain and opioid use in the form of total morphine sulfate equivalents were reduced significantly in treated patients ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2338251

Cannabinoids for Medical Use: A Systematic Review and ... The average number of patients who reported a reduction in pain of at least 30% was greater with cannabinoids than with placebo (OR, 1.41 [95% CI, 0.99-2.00]; 8 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06454669?term=tetrahydrocannabinol&aggFilters=status:rec%20enr%20act&viewType=Table&rank=4

Dronabinol as an Adjunct for Reducing Pain Collectively, these data suggest that cannabinoids may be more effective for chronic rather than acute pain conditions. However, there have been few randomized, ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1526590015008378

Cannabis for the Management of Pain: Assessment ... The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5804828/

Dronabinol Is a Safe Long-Term Treatment Option for ... Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and ...

8. acog.org acog.org/clinical/clinical-guidance/clinical-consensus/articles/2024/07/the-use-of-cannabis-products-for-the-management-of-pain-associated-with-gynecologic-conditions

The Use of Cannabis Products for the Management of Pain ... More and better-quality data on the efficacy and safety of the use of cannabis products for the management of gynecologic pain, including menstrual phase– ...

9. fda.gov fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd

FDA Regulation of Cannabis and ... FDA's Cannabis Product Committee (CPC) develops and implements cross-Agency strategy and policy for the regulation of cannabis products.