Dronabinol for Chronic Low Back Pain

(DARP Trial)

Recruiting at 1 trial location

Overseen By Adetola O Vaughan, MA

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Christopher D. Verrico

Must not be taking: Cannabinoids, Antiepileptics, Benzodiazepines, others

Disqualifiers: Cannabis use, Psychiatric illness, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

75 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires you to stop using cannabis, marijuana, and any cannabinoids, including over-the-counter CBD products. You also cannot use certain medications like antiepileptic drugs, barbiturates, benzodiazepines, and some antidepressants. If you're on a stable pain treatment for at least 3 months, you can continue with that.

What evidence supports the effectiveness of the drug dronabinol for chronic low back pain?

Research shows that dronabinol, a form of THC, can help reduce pain intensity and increase satisfaction in patients with chronic pain who are also taking opioids. This suggests it might be effective for chronic low back pain as well. ^{1 2 3 4 5}

Is dronabinol safe for treating chronic low back pain?

Dronabinol has been shown to be generally safe in humans, with common side effects including dry mouth, dizziness, and headache, which are usually mild to moderate and temporary. Long-term use in patients with neuropathic pain showed no signs of drug abuse and only one possible case of dependency, suggesting it is a safe option for managing chronic pain. ^{2 6 7 8 9}

How does the drug dronabinol differ from other treatments for chronic low back pain?

Dronabinol is unique because it is a synthetic form of delta-9-tetrahydrocannabinol (THC), a compound found in cannabis, and is used as an add-on treatment to enhance pain relief in patients already taking opioids. Unlike standard painkillers, it offers an alternative mechanism by interacting with the body's endocannabinoid system, which may provide additional pain relief and increased patient satisfaction. ^{1 3 4 10 11}

What is the purpose of this trial?

This exploratory, proof-of-concept study is a double-blind (participants and investigators will be blinded), placebo-controlled, randomized, two-arm clinical trial of Marinol \[dronabinol, synthetic Δ9-tetrahydrocannabinol (THC)\] for chronic low back pain (cLBP) with a 2:1 allocation ratio. Up to 75 subjects will be enrolled in this pilot study and randomized to receive doses of THC (up to 30 mg/day), orally, over 8 weeks. This study will be conducted at a single site; it does not include any stratifications, and there is no interim analysis planned. Notably, the goal is to determine whether there is enough evidence of the safety of THC to support the development of later-phase clinical trials. Thus, detailed developmental plans are contingent on the outcomes of this study.

Research Team

Christopher D Verrico, phD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for adults with chronic low back pain or a back injury. Participants must be willing to take oral medication and be available for the full 8-week study period. People who are pregnant, breastfeeding, have certain mental health conditions, or use substances that could interact with THC are not eligible.

Inclusion Criteria

I am willing and able to follow the study rules and attend all required visits.

My pain management treatment has been the same for the last 3 months.

For females of reproductive potential: currently practicing an effective form of two types of birth control for at least 1 month prior to screening and agrees to use such a method during study participation and for an additional 4 weeks after the end of study medication administration unless she is surgically sterile, partner is surgically sterile, or she is postmenopausal

Exclusion Criteria

Systolic blood pressure > 140 mm Hg, or diastolic blood pressure > 90 mm Hg

I currently use cannabis or CBD products and do not want to stop.

I am not allergic to cannabis, CBD, THC, or related substances.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dronabinol or placebo capsules, up to 15 mg, twice per day for 8 weeks

8 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dronabinol

Trial Overview The trial is testing Dronabinol (synthetic THC) against a placebo to see if it can help reduce chronic lower back pain. Participants will either receive up to 30 mg/day of Dronabinol or a placebo over an 8-week period in a blinded study where neither they nor the investigators know who's receiving the actual drug.

Participant Groups

Group I: Drug: Dronabinol Experimental Treatment 1 Intervention

Dronabinol capsules, over-encapsulated with filler to match the appearance of the placebo capsule, up to 15 mg, twice per day for 8 weeks.

Group II: Placebo Placebo Group 1 Intervention

Capsules with placebo (i.e., cellulose filler), twice per day for 8 weeks.

Who Is Running the Clinical Trial?

Christopher D. Verrico

Lead Sponsor

Trials

2

Recruited

120+

Findings from Research

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 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]

Current evidence does not support the effectiveness of cannabidiol (CBD) for treating acute low back pain, as a clinical trial showed no significant difference compared to placebo.

While there are indications that CBD may help relieve chronic low back pain, the overall evidence is still weak, highlighting the need for more rigorous randomized controlled trials to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can cannabidiol (CBD) help with low back pain? Kulesza, B., Mazurek, M., Kurzepa, J.[2023]

A study of 26 prescribers across France revealed that dronabinol is primarily prescribed for chronic pain related to multiple sclerosis (49.7%) and central neuropathic pain (36.6%), with an average treatment duration of 1 month to 6 years.

About 59% of patients reported a significant reduction in pain (30 to 50%), indicating that dronabinol may be an effective option for managing refractory chronic pain, but further research is needed to optimize its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol use in France between 2004 and 2017. Lejczak, S., Rousselot, H., Di Patrizio, P., et al.[2020]

In a study involving 20 chronic pain patients with fibromyalgia, inhaled cannabis did not show significant analgesic effects compared to placebo, although the Bediol variety led to a 30% decrease in pain scores for some patients.

Cannabis containing THC increased pressure pain thresholds, but the presence of CBD appeared to reduce the overall pain-relieving effects of THC, highlighting complex interactions between these cannabinoids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. van de Donk, T., Niesters, M., Kowal, MA., et al.[2022]

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]

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]

A systematic review of 43 randomized controlled trials involving 4436 participants found that current cannabinoid trials for chronic pain often fail to meet key safety reporting standards, with an average of 3 to 4 CONSORT guidelines not being followed.

Many trials lacked adequate assessment and reporting of adverse events, with 17 trials not detailing their methods for assessing adverse events and 14 trials failing to report serious adverse events, highlighting a significant gap in safety evaluation in cannabinoid research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to Consolidated Standards of Reporting Trials (CONSORT) Guidelines for Reporting Safety Outcomes in Trials of Medical Cannabis and Cannabis-based Medicines for Chronic Noncancer Pain: A Systematic Review. Mohiuddin, MM., Mizubuti, GB., Haroutounian, S., et al.[2021]

Dronabinol (Δ9-THC) shows potential as an analgesic for chronic pain, but its effectiveness varies due to different pain mechanisms, highlighting the need for a deeper understanding of how it works in the body.

The review emphasizes the importance of developing objective biomarkers to assess the effects of dronabinol on pain, which could help identify which patients are likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dronabinol and chronic pain: importance of mechanistic considerations. de Vries, M., van Rijckevorsel, DC., Wilder-Smith, OH., et al.[2018]

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 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]

References

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

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. [2013]

2. Switzerland 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. [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

Can cannabidiol (CBD) help with low back pain? [2023]

4. France pubmed.ncbi.nlm.nih.gov

Dronabinol use in France between 2004 and 2017. [2020]

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

An experimental randomized study on the analgesic effects of pharmaceutical-grade cannabis in chronic pain patients with fibromyalgia. [2022]

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

The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. [2022]

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

Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. [2018]

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

Adherence to Consolidated Standards of Reporting Trials (CONSORT) Guidelines for Reporting Safety Outcomes in Trials of Medical Cannabis and Cannabis-based Medicines for Chronic Noncancer Pain: A Systematic Review. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Dronabinol and chronic pain: importance of mechanistic considerations. [2018]

10. France pubmed.ncbi.nlm.nih.gov

[Use of dronabinol in the treatment of resistant neuropathic pain: Feedback from patients followed in a multidisciplinary pain center]. [2023]

11. England 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. [2022]