THC for Pain Relief in Older Adults

Overseen By Julia Meyerovich, M.S.

Age: 65+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Pain drugs, CYP2C9 inducers

Disqualifiers: Psychiatric disorders, Respiratory problems, Neurological conditions, others

Compensation: Varies

Number of Visits: 6

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using any current medications that affect pain or interact with certain liver enzymes (like carbamazepine, valproate, fluvoxamine, and paroxetine).

What evidence supports the effectiveness of the drug THC for pain relief in older adults?

Research shows that dronabinol, a form of THC, can help reduce pain intensity and improve satisfaction in patients with chronic pain who are also taking opioids. Additionally, THC has been found to improve pain and quality of life in patients with chronic pain conditions like neuropathy and fibromyalgia, suggesting it may be a promising option for pain management. ^{1 2 3 4 5}

Is THC safe for older adults?

THC, including forms like dronabinol and Namisol, is generally safe and well-tolerated in older adults, though it may cause mild side effects like drowsiness and dry mouth. Long-term use of dronabinol has been shown to be safe, with no signs of drug abuse or dependency. ^{1 6 7 8 9}

How does the drug Dronabinol differ from other pain relief options for older adults?

Dronabinol, a synthetic form of THC, is unique because it targets pain through mechanisms involving the body's cannabinoid receptors, which may alter pain perception and reduce pain intensity. Unlike traditional pain medications, it can be used as an add-on to existing opioid therapy, potentially enhancing pain relief and reducing the need for higher opioid doses. ^{1 2 3 7 10}

What is the purpose of this trial?

The overarching goal of this double-blind, placebo-controlled, crossover study is to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) effects of the main analgesic and psychoactive constituent of cannabis, delta-9 tetrahydrocannabinol (THC), among older adults - the fastest growing population of cannabis consumers, and the most likely age cohort to use cannabinoids to relieve pain. The research will proceed with a sub-study, randomizing 20 men and women aged 65 years or older, to two doses focusing on oral THC administration and a sub-study randomizing 20 men and women aged 65 years or older, to two doses focusing on vaporized THC administration.

Research Team

Joao P. De Aquino, M.D.

Principal Investigator

Yale University

Eligibility Criteria

This trial is for healthy adults aged 65 or older who have used THC or cannabis at least once in the last decade. They must be able to consent and speak English. People with abnormal heart tests, psychiatric disorders, regular use of certain drugs affecting pain perception, serious medical conditions, allergies to sesame oil/THC/cannabis, neurological issues affecting pain response/balance, untreated high blood pressure, or major cognitive disorders cannot join.

Inclusion Criteria

I am 65 years old or older and in good health.

Prior exposure to THC or cannabis at least once in the last 10 years; 1-10 times in the last 20 years; or more than 20 times in their lifetime

I can understand and sign the consent form in English.

Exclusion Criteria

I have a condition like asthma or COPD that can cause breathing problems.

Major neurocognitive disorders precluding participation, evidenced by a clinical exam

I do not have major health issues like liver or kidney problems, immune system disorders, or a history of seizures or serious head injuries.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Oral THC Sub-Study

Participants receive two doses of oral THC (5 mg and 10 mg) across three 8-hour test sessions

3 sessions

3 visits (in-person)

Vaporized THC Sub-Study

Participants receive two doses of vaporized THC (2 mg and 4 mg) across three 8-hour test sessions

3 sessions

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dronabinol
• Placebo
• Purified THC in an ethanolic solution

Trial Overview The study is testing how different doses of THC (2mg and 4mg) taken orally or vaporized affect older adults compared to a placebo. It's looking at how quickly THC enters the bloodstream (PK) and its effects on pain tolerance and potential for abuse (PD). Participants will try each form under controlled conditions.

Participant Groups

Group I: Dronabinol 5mg Active Control 1 Intervention

Dronabinol 5 mg

Group II: Vaporized THC 4mg Active Control 1 Intervention

Vaporized THC 4 mg

Group III: Vaporized THC 2mg Active Control 1 Intervention

Vaporized THC 2mg

Group IV: Dronabinol 10mg Placebo Group 1 Intervention

Dronabinol 10 mg

Group V: Placebo Placebo Group 1 Intervention

Masked oral placebo or vaporized saline

Dronabinol is already approved in United States, Canada for the following indications:

Approved in United States as Marinol for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting
• Sleep apnea

Approved in United States as Syndros for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Approved in Canada as REDUVO for:

• HIV/AIDS-induced anorexia
• Chemotherapy-induced nausea and vomiting

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

VA Connecticut Healthcare System

Collaborator

Trials

86

Recruited

8,800+

Findings from Research

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 involving 172 patients over 7 months, delta 9-Tetrahydrocannabinol (delta 9-THC) significantly improved pain intensity and quality of life measures in those with central neuropathic pain, with many patients reporting reduced opioid use.

While delta 9-THC was generally perceived as effective with tolerable side effects, about 25% of patients experienced difficulties tolerating the treatment, highlighting the need for careful titration and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey. Weber, J., Schley, M., Casutt, M., et al.[2021]

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]

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 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 phase 1 trial involving 12 healthy older adults (average age 72), the THC-based drug Namisol(®) was found to be safe and well tolerated, with drowsiness and dry mouth being the most common side effects.

Higher doses of THC (6.5mg) led to more adverse events compared to lower doses (3mg and 5mg), indicating that while THC is generally safe, careful dosing is important for older individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: a randomized controlled trial. Ahmed, AI., van den Elsen, GA., Colbers, A., et al.[2014]

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 double-blind crossover trial involving 13 patients with chronic upper motor neuron syndrome, low-dose Nabilone (1 mg per day) significantly reduced spasticity-related pain compared to placebo, demonstrating its efficacy in this challenging condition.

Nabilone was found to be safe, with only mild side effects reported, making it a viable treatment option for patients who do not respond well to conventional pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. Wissel, J., Haydn, T., Müller, J., et al.[2018]

In a phase 2 trial involving 65 patients with chronic abdominal pain, THC tablets did not show a significant difference in pain relief compared to placebo, with both groups experiencing similar reductions in pain scores over 50-52 days.

THC was found to be safe and well-tolerated, although more patients in the THC group discontinued due to mild or moderate adverse events compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. de Vries, M., van Rijckevorsel, DCM., Vissers, KCP., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey. [2021]

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

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. [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. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: a randomized controlled trial. [2014]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. Germany pubmed.ncbi.nlm.nih.gov

Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. [2018]

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

Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. [2018]