THC for Pain Relief in Older Adults
Recruiting in Palo Alto (17 mi)
Overseen byJoao P. De Aquino, M.D.
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Yale University
Must not be taking: Pain drugs, CYP2C9 inducers
Disqualifiers: Psychiatric disorders, Respiratory problems, Neurological conditions, others
Trial Summary
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.
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.
12345Is 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.
16789How 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.
123710Eligibility 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.
+14 more
Trial 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
Participant Groups
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.
5Treatment groups
Active Control
Placebo Group
Group I: Dronabinol 5mgActive Control1 Intervention
Dronabinol 5 mg
Group II: Vaporized THC 4mgActive Control1 Intervention
Vaporized THC 4 mg
Group III: Vaporized THC 2mgActive Control1 Intervention
Vaporized THC 2mg
Group IV: Dronabinol 10mgPlacebo Group1 Intervention
Dronabinol 10 mg
Group V: PlaceboPlacebo Group1 Intervention
Masked oral placebo or vaporized saline
Dronabinol is already approved in United States, United States, Australia, 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 Australia as Marinol 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
VA Connecticut Healthcare SystemWest Haven, CT
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
National Institute on Drug Abuse (NIDA)Collaborator
VA Connecticut Healthcare SystemCollaborator
References
Dronabinol and chronic pain: importance of mechanistic considerations. [2018]Although medicinal cannabis has been used for many centuries, the therapeutic potential of delta-9-tetrahydrocannabinol (Δ9-THC; international non-proprietary name = dronabinol) in current pain management remains unclear. Several pharmaceutical products with defined natural or synthesized Δ9-THC content have been developed, resulting in increasing numbers of clinical trials investigating the analgesic efficacy of dronabinol in various pain conditions. Different underlying pain mechanisms, including sensitization of nociceptive sensory pathways and alterations in cognitive and autonomic processing, might explain the varying analgesic effects of dronabinol in chronic pain states.
Tetrahydrocannabinol (Delta 9-THC) Treatment in Chronic Central Neuropathic Pain and Fibromyalgia Patients: Results of a Multicenter Survey. [2021]Central neuropathic pain is difficult to treat, but delta 9-Tetrahydrocannabinol (delta 9-THC) may be a promising therapeutic agent. We administered in 172 patients on average 7.5 mg delta 9-THC over 7 months. Of these, 48 patients prematurely withdrew due to side effects, insufficient analgesia, or expense of therapy. Thus, 124 patients were assessed retrospectively in a multicenter telephone survey. Reported changes in pain intensity, recorded on a numeric rating scale (NRS), Pain Disability Index (PDI), Medical Outcomes Short-Form (SF-12), Quality of Life Impairment by Pain (QLIP), Hospital Anxiety Depression Scale (HADS), and amount of concomitant pain medication were recorded. Psychometric parameters (PDI, SF-12, QLIP, HADS) and pain intensity improved significantly during delta 9-THC treatment. Opioid doses were reduced and patients perceived THC therapy as effective with tolerable side effects. About 25% of the patients, however, did not tolerate the treatment. Therapy success and tolerance can be assessed by a transient delta 9-THC titration and its maintained administration for several weeks. The present survey demonstrates its ameliorating potential for the treatment of chronic pain in central neuropathy and fibromyalgia. A supplemental delta 9-THC treatment as part of a broader pain management plan therefore may represent a promising coanalgesic therapeutic option.
Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy. [2013]We assessed the efficacy of dronabinol (Marinol capsules; Solvay Pharmaceuticals, Brussels, Belgium), a synthetic Delta(9)-THC (tetrahydrocannabinol), in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment. Phase I of this 2-phase study was a randomized, single-dose, double-blinded, placebo-controlled, crossover trial in which subjects were randomly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three, 8-hour visits. Baseline self-report measures, hourly ratings of pain intensity, pain relief, pain bothersomeness, treatment satisfaction, mood, side effects, and blood serum levels were obtained. Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids. Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo. No differences in benefit were found between the 20 mg and 10 mg doses. In the Phase II trial, titrated dronabinol contributed to significant relief of pain, reduced pain bothersomeness, and increased satisfaction compared with baseline. The incidence of side effects was dose-related. Overall, the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain.
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]To date, the therapeutic use of cannabinoids in chronic pain management remains controversial owing to the limited clinical evidence found in randomized clinical trials (RCTs), the heterogeneous nature of the clinical indication, and the broad range of cannabis-based medicinal products (CBMPs) used in both experimental and observational clinical studies. Here we evaluate patient-reported clinical outcomes (PROMS) in a cohort of adult patients, diagnosed with chronic pain of diverse etiology, who received adjuvant treatment with oral, cannabis-based, magistral formulations between May and September 2021 at the Latin American Institute of Neurology and Nervous System (ILANS-Zerenia) in Bogotá, Colombia. During this period, 2,112 patients completed a PROMS questionnaire aimed at capturing the degree of clinical improvement of their primary symptom and any potential side effects. Most participants were female (76.1%) with an average age of 58.7 years old, and 92.5% (1,955 patients) reported some improvement in their primary symptom (p < 0.001). Two monovarietal, full-spectrum, cannabis formulations containing either cannabidiol (CBD 30 mg/mL; THC <2 mg/mL) or a balanced composition (THC 12 mg/mL; CBD 14 mg/mL) accounted for more than 99% of all prescriptions (59.5 and 39.8%, respectively). The degree of improvement was similar between both formulations, although males reported less effectiveness in the first 4 weeks of treatment. Sex-specific differences were also found in prescription patterns, with male patients increasing the intake of the balanced chemotype overtime. For many patients (71.7%) there were no adverse side effects associated to the treatment and those most reported were mild, such as somnolence (13.0%), dizziness (8.1%) and dry mouth (4.2%), which also appeared to fade over time. Our results constitute the first real-world evidence on the clinical use of medicinal cannabis in Colombia and suggest that cannabis-based oral magistral formulations represent a safe and efficacious adjuvant therapeutic option in the management of chronic pain.
Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. [2022]Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabis based medicine, nabilone, dronabinol and a novel THC analogue. Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met the inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required.
The Safety of Dronabinol and Nabilone: A Systematic Review and Meta-Analysis of Clinical Trials. [2022]Dronabinol, a natural cannabinoid, and its semi-synthetic derivative, nabilone, are marketed as medicines in several countries. The aim of our work was to systematically evaluate the frequency of adverse events related to dronabinol or nabilone treatment compared to placebo. Scientific databases were searched for placebo-controlled clinical studies of patients receiving either dronabinol or nabilone therapy with placebo control groups. This meta-analysis was reported following the PRISMA guidelines using the PICO format, and it was registered with the PROSPERO register. There were 16 trials included in the meta-analysis. In the nabilone studies, drowsiness was more than 7 times as frequent in patients treated with nabilone than in the placebo group (OR: 7.25; 95% CI: 1.64-31.95), and the risk of dizziness (OR: 21.14; 95% CI: 2.92-152.75) and dry mouth was also higher (OR: 17.23; 95% CI: 4.33-68.55). The frequency of headache was not different in the two groups. In case of dronabinol, the frequency of dry mouth (OR: 5.58; 95% CI: 3.19-9.78), dizziness (OR: 4.60 95% CI: 2.39-8.83) and headache (OR: 2.90; 95% CI: 1.07-7.85) was significantly higher in the dronabinol groups, whereas in case of nausea, drowsiness and fatigue there was no difference. The severity of adverse events was typically mild-to-moderate and transient. In a risk-benefit assessment, these adverse effects are acceptable compared to the achievable benefit. However, considering the diversity of the adverse effects, more studies are needed to provide a more accurate assessment on the side effect profiles of these two compounds.
Safety and pharmacokinetics of oral delta-9-tetrahydrocannabinol in healthy older subjects: a randomized controlled trial. [2014]There is a great concern about the safety of THC-based drugs in older people (≥65 years), as most of THC-trials did not include such group. In this phase 1, randomized, double-blind, double-dummy, placebo-controlled, cross-over trial, we evaluated the safety and pharmacokinetics of three oral doses of Namisol(®), a novel THC in tablet form, in older subjects. Twelve healthy older subjects (6 male; mean age 72±5 years) randomly received a single oral dose of 3mg, 5mg, or 6.5mg of THC or matching placebo, in a crossover manner, on each intervention day. The data for 11 subjects were included in the analysis. The data of 1 subject were excluded due to non-compliance to study medication. THC was safe and well tolerated. The most frequently reported adverse events (AEs) were drowsiness (27%) and dry mouth (11%). Subjects reported more AEs with THC 6.5mg than with 3mg (p=0.048), 5mg (p=0.034) and placebo (p=0.013). There was a wide inter-individual variability in plasma concentrations of THC. Subjects for whom the Cmax fell within the sampling period (over 2h), Cmax was 1.42-4.57ng/mL and Tmax was 67-92min. The AUC0-2h (n=11) was 1.67-3.51ng/mL. Overall, the pharmacodynamic effects of THC were smaller than effects previously reported in young adults. In conclusion, THC appeared to be safe and well tolerated by healthy older individuals. Data on safety and effectiveness of THC in frail older persons are urgently required, as this population could benefit from the therapeutic applications of THC.
Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients. [2018]Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis (MS) is frequently insufficient. Yet, cannabis is still rarely offered for treatment of pain. This clinical trial aimed at showing the positive benefit-risk ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16-weeks placebo-controlled phase-III study followed by a 32-weeks open-label period. One hundred patients continued therapy for overall up to 119 weeks. Primary endpoint was change of pain intensity on the 11-point Numerical Rating Scale over a 16-weeks treatment period. Safety was assessed on the basis of adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16-weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points without significant difference in between (p = 0.676). Although the proportion of patients with ARs was higher under dronabinol compared to placebo (50.0 vs. 25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug abuse and only one possible case of dependency occurred. The trial results demonstrate that dronabinol is a safe long-term treatment option.
Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. [2018]About 30% of patients with chronic upper motor neuron syndrome (UMNS) suffer from disabling spasticity-related pain not sufficiently correctable by conventional treatment. Delta9-tetrahydrocannabinol (Delta(9)-THC) was reported to add benefit in the treatment of pain in patients with multiple sclerosis (MS). The question arose whether synthetic cannabinoids with lower potential for psychotropic side effects could be effective as well. To evaluate the safety and efficacy of low dose treatment with the synthetic cannabinoid Nabilone (1 mg per day) on spasticity-related pain a placebo-controlled double-blind crossover trial was performed.11 out of 13 included patients completed the study. The 11-Point-Box-Test showed a significant decrease of pain under Nabilone (p
Tetrahydrocannabinol Does Not Reduce Pain in Patients With Chronic Abdominal Pain in a Phase 2 Placebo-controlled Study. [2018]Delta-9-tetrahydrocannabinol (THC) is the most abundant cannabinoid from the plant Cannabis sativa. There is only equivocal evidence that THC has analgesic effects. We performed a phase 2 controlled trial to evaluate the analgesic efficacy, pharmacokinetics, safety, and tolerability of an oral tablet containing purified THC in patients with chronic abdominal pain.