Dronabinol for Knee Surgery Pain

Overseen By Vehniah K Tjong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Northwestern University

Must not be taking: Anticholinergics, Benzodiazepines, SSRIs, others

Disqualifiers: Pregnancy, Lactose intolerance, Mental health, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether dronabinol, a medication, can manage pain after knee surgery and reduce opioid use. The researchers aim to determine if it effectively reduces pain with minimal side effects. Individuals undergoing specific knee surgeries, such as meniscectomy or synovectomy, might be suitable candidates. Participants must avoid marijuana and alcohol during the study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking pain management solution.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, such as anticholinergic agents, benzodiazepines, and others listed in the trial's exclusion criteria. Additionally, you must avoid using marijuana products, CBD, and alcohol during the study.

Is there any evidence suggesting that dronabinol is likely to be safe for humans?

Research has shown that dronabinol, a synthetic version of THC, has been studied for pain relief. In one study, patients already using opioids for long-term pain experienced reduced pain with dronabinol. This finding suggests it might also help manage pain after knee surgery.

Another study examined dronabinol use after surgery and found it caused few negative side effects. Most patients tolerated it well, with few discontinuing due to side effects. This outcome was similar to that of patients taking a placebo, which contains no active drug.

While dronabinol is being tested for post-surgical pain, its use in other conditions supports its safety. Overall, current evidence suggests that dronabinol is generally well-tolerated with few major side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard pain management options for post-knee surgery, which typically include opioids and non-steroidal anti-inflammatory drugs, dronabinol is derived from cannabis. Researchers are excited about dronabinol because it targets the body's endocannabinoid system, potentially offering pain relief with fewer side effects than traditional opioids. This unique mechanism of action could lead to a safer alternative for managing pain, reducing the risk of addiction and other complications associated with current treatments.

What evidence suggests that dronabinol might be an effective treatment for knee surgery pain?

Research has shown that dronabinol, a synthetic form of THC (the active ingredient in cannabis), can help reduce pain. One study found that patients using dronabinol for long-term pain experienced significant relief and required fewer opioids. In this trial, some participants will receive dronabinol to assess its effectiveness in managing pain after knee surgery, potentially reducing opioid use. Although dronabinol has primarily been studied for long-term pain, its potential benefits for surgery-related pain appear promising. ^{1 2 3 5 6}

Who Is on the Research Team?

Vehniah K Tjong, MD

Principal Investigator

Northwestern Feinberg School of Medicine

Are You a Good Fit for This Trial?

Adults over 18 scheduled for knee arthroscopic surgery can join this trial. They must avoid alcohol, recreational or medical marijuana, CBD products, and certain medications during the study. Pregnant women, those breastfeeding or trying to conceive are excluded, as well as patients with allergies to study drugs, lactose intolerance, severe mental health conditions or substance abuse issues.

Inclusion Criteria

I am scheduled for a knee surgery that may include procedures like Meniscectomy or Chondroplasty.

Exclusion Criteria

I am unable to give consent for medical procedures.

I am under 18 years old.

I am having or have had an open surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dronabinol or placebo twice a day for 7 days in addition to standard pain medication protocol after arthroscopic knee surgery

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain behavior, pain interference, and physical function

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dronabinol
• Placebo

Trial Overview

The trial is testing if Dronabinol helps with pain after knee surgery compared to a placebo. It aims to see if it reduces the need for opioids and has minimal side effects. If successful in reducing postoperative pain without significant negative effects, the scope may broaden to other surgeries.

How Is the Trial Designed?

Group I: Dronabinol Experimental Treatment 1 Intervention

Patients will received dronabinol (5mg) twice a day for 7 days in addition to standard pain medication protocol after arthroscopic knee surgery

Group II: Placebo Placebo Group 1 Intervention

Patients will received placebo twice a day for 7 days in addition to standard pain medication protocol after arthroscopic knee surgery

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Published Research Related to This Trial

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 involving 40 women after abdominal hysterectomy, a single dose of 5 mg oral delta-9-THC did not show significant analgesic effects compared to a placebo, as measured by pain intensity scores at 6 hours post-administration.

While delta-9-THC did not provide pain relief, it was associated with increased awareness of surroundings in 40% of patients, compared to only 5% in the placebo group, indicating a potential psychoactive effect without analgesic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Buggy, DJ., Toogood, L., Maric, S., et al.[2019]

A systematic review of 36 studies involving 7217 participants found limited evidence supporting the efficacy of cannabinoids, cannabis, and cannabis-based medicines for pain management, with only short-term cannabis use showing a potential benefit.

Most studies had a high or uncertain risk of bias, and adverse events were more common with cannabinoid treatments compared to controls, leading to low confidence in the overall effectiveness and safety of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials. Fisher, E., Moore, RA., Fogarty, AE., et al.[2023]

In a study of 81 patients who received dronabinol after total joint arthroplasty, the average length of hospital stay was significantly shorter (2.3 days) compared to a matched control group (3.0 days), suggesting potential benefits in recovery time.

Patients taking dronabinol also consumed significantly fewer opioid morphine equivalents (252.5 mg) than those in the control group (313.3 mg), indicating that dronabinol may help reduce opioid use without reported side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should Cannabinoids Be Added to Multimodal Pain Regimens After Total Hip and Knee Arthroplasty? Hickernell, TR., Lakra, A., Berg, A., et al.[2019]

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 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 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 195 patients undergoing total hip and knee arthroplasty, 16.4% reported using CBD/THC products during the perioperative period, with higher usage in knee arthroplasty patients (22.6%) compared to hip arthroplasty patients (11.7%).

Despite the use of CBD/THC products, there was no significant difference in opioid consumption, pain scores, or length of hospital stay between users and non-users, suggesting that these products may not significantly impact post-operative opioid requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Tetrahydrocannabinol and Cannabidiol Products in the Perioperative Period Around Primary Unilateral Total Hip and Knee Arthroplasty. Runner, RP., Luu, AN., Nassif, NA., et al.[2021]

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 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]

Citations

1.

asra.com

asra.com/docs/default-source/events-education-documents/raapm24/abstract-5291.pdf?sfvrsn=ca613353_1

Effects of Perioperative Dronabinol Use in Total Knee ...

The primary outcome was opioid consumption (in morphine milligram equivalents) 24-48 hours after surgery. Additional secondary outcomes included cumulative ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05335252

NCT05335252 | Dronabinol After Arthroscopic Surgery

The investigators hypothesize that dronabinol will relieve pain, reduce opioid consumption and will result in few negative side effects. If this pilot study ...

3.

withpower.com

withpower.com/trial/phase-3-wounds-and-injuries-4-2022-ab68f

Dronabinol for Knee Surgery Pain

In a study involving 30 patients on opioids for chronic pain, dronabinol (synthetic THC) was found to significantly reduce pain intensity and increase treatment ...

4.

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, ...

5.

academic.oup.com

academic.oup.com/painmedicine/advance-article/doi/10.1093/pm/pnaf110/8238175

Cannabis and cannabidiol for postoperative pain ...

Cannabis users in surgical populations have often presented with higher preoperative pain and opioid use, though other studies have shown similar or even ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12472909/

Cannabinoids in Chronic Pain: Clinical Outcomes, Adverse ...

Quantitative data show that discontinuation rates range from 4.3% at low-dose CBD to 12.9% at high-dose CBD, compared with 3.5% on placebo, ...