Dataset Information

Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

ABSTRACT: The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delta-9-tetrahydrocannabinol (dronabinol), as well as their effects on physical and cognitive functioning, and human abuse potential (HAP) outcomes among individuals with knee osteoarthritis (KOA). This was a within-subject, double-blind, randomized, placebo-controlled study. Participants (N = 37; 65% women; mean age = 62) diagnosed with knee osteoarthritis of ≥3/10 average pain intensity were included. Participants received (1) placebo-placebo, (2) hydromorphone (4 mg)-placebo; (3) dronabinol (10 mg)-placebo, and (4) hydromorphone (4 mg)-dronabinol (10 mg). Clinical and experimentally-induced pain, physical and cognitive function, subjective drug effects, HAP, adverse events, and pharmacokinetics were evaluated. No significant analgesic effects were observed for clinical pain severity or physical functioning across all drug conditions. Little enhancement of hydromorphone analgesia by dronabinol was observed on evoked pain indices. While subjective drug effects and some HAP ratings were increased in the combined drug condition, these were not significantly increased over the dronabinol alone condition. No serious adverse events were reported; hydromorphone produced more mild adverse events than placebo, but hydromorphone + dronabinol produced more moderate adverse events than both placebo and hydromorphone alone. Only hydromorphone impaired cognitive performance. Consistent with laboratory studies on healthy adults, the present study shows minimal benefit of combining dronabinol (10 mg) and hydromorphone (4 mg) for analgesia and improving physical functioning in adults with KOA.

SUBMITTER: Campbell CM

PROVIDER: S-EPMC10516978 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

Campbell Claudia M CM Mun Chung Jung CJ Hamilton Katrina R KR Bergeria Cecilia L CL Huhn Andrew S AS Speed Traci J TJ Vandrey Ryan R Dunn Kelly E KE

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20230518 11

The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delta-9-tetrahydrocannabinol (dronabinol), as well as their effects on physical and cognitive functioning, and human abuse potential (HAP) outcomes among individuals with knee osteoart ...[more]

PMID: 37202479

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Project description:This Phase II study evaluated analgesia, abuse liability, and cognitive performance of hydromorphone and oral delta-9-tetrahydrocannabinol (THC; dronabinol) using a within-subject, double-blind, randomized, placebo-controlled, human laboratory trial. Healthy adults (N = 29) with no history of drug use disorder received combinations of placebo, hydromorphone (4 mg; oral), and dronabinol (2.5 mg, 5.0 mg, 10 mg; oral). Primary outcomes were quantitative sensory testing (QST) measures of acute (thermal, pressure pain; thermal, punctate probe temporal summation; cold pressor; conditioned pain modulation) and chronic pain (capsaicin 10% topical cream with thermal rekindling), measures of drug abuse liability, cognitive functioning, and adverse events. Subgroup analyses were conducted within opioid-responders (endorsed >20 on a Drug Effect visual analog scale during the hydromorphone-only condition) and nonresponders. A consistent dose-effect relationship of dronabinol on hydromorphone across all measures was not observed. Analgesia only improved in the hydromorphone + dronabinol 2.5 mg condition. Hydromorphone + dronabinol 2.5 mg showed the lowest and hydromorphone+dronabinol 5 mg showed the highest risk for abuse. Hydromorphone+dronabinol 10 mg produced a high rate of dysphoric effects, and hydromorphone+dronabinol 5 mg and hydromorphone + dronabinol 10 mg produced AEs. Subgroup analyses showed subjective effects and abuse risk was increased among opioid responders and largely absent among nonresponders. Overall, only hydromorphone+dronabinol 2.5 mg modestly enhanced hydromorphone-based analgesia and hydromorphone + dronabinol 5 mg and 10 mg increased risk for abuse and AEs. These data can help inform opioid-sparing efforts in clinical pain populations. Demonstration that potential opioid effects varied as a function of participant opioid sensitivity (e.g., responder status) is a novel finding that warrants additional research.

Project description:Background & aimsThe skeletal muscle anabolic effects of n-3 polyunsaturated fatty acids (n-3 PUFA) appear favoured towards women; a property that could be exploited in older women who typically exhibit poor muscle growth responses to resistance exercise training (RET). Here we sought to generate novel insights into the efficacy and mechanisms of n-3 PUFA alongside short-term RET in older women.MethodsWe recruited 16 healthy older women (Placebo n = 8 (PLA): 67±1y, n-3 PUFA n = 8: 64±1y) to a randomised double-blind placebo-controlled trial (n-3 PUFA; 3680 mg/day versus PLA) of 6 weeks fully-supervised progressive unilateral RET (i.e. 6 × 8 reps, 75% 1-RM, 3/wk-1). Strength was assessed by knee extensor 1-RM and isokinetic dynamometry ∼ every 10 d. Thigh fat free mass (TFFM) was measured by DXA at 0/3/6 weeks. Bilateral vastus lateralis (VL) biopsies at 0/2/4/6 weeks with deuterium oxide (D2O) dosing were used to determine MPS responses for 0-2 and 4-6 weeks. Further, fibre cross sectional area (CSA), myonuclei number and satellite cell (SC) number were assessed, alongside muscle anabolic/catabolic signalling via immunoblotting.ResultsRET increased 1-RM equally in the trained leg of both groups (+23 ± 5% n-3 PUFA vs. +25 ± 5% PLA (both P < 0.01)) with no significant increase in maximum voluntary contraction (MVC) (+10 ± 6% n-3 PUFA vs. +13 ± 5% PLA). Only the n-3 PUFA group increased TFFM (3774 ± 158 g to 3961 ± 151 g n-3 PUFA (P < 0.05) vs. 3406 ± 201 g to 3561 ± 170 PLA) and type II fibre CSA (3097 ± 339 μm2 to 4329 ± 264 μm2 n-3 PUFA (P < 0.05) vs. 2520 ± 316 μm2 to 3467 ± 303 μm2 in PL) with RET. Myonuclei number increased equally in n-3 PUFA and PLA in both type I and type II fibres, with no change in SC number. N-3 PUFA had no added benefit on muscle protein synthesis (MPS), however, during weeks 4-6 of RET, absolute synthesis rates (ASR) displayed a trend to increase with n-3 PUFA only (5.6 ± 0.3 g d-1 to 7.1 ± 0.5 g d-1 n-3 PUFA (P = 0.09) vs. 5.5 ± 0.5 g d-1 to 6.5 ± 0.5 g d-1 PLA). Further, the n-3 PUFA group displayed greater 4EBP1 activation after acute RE at 6 weeks.Conclusionn3-PUFA enhanced RET gains in muscle mass through type II fibre hypertrophy, with data suggesting a role for MPS rather than via SC recruitment. As such, the present study adds to a literature base illustrating the apparent enhancement of muscle hypertrophy with RET in older women fed adjuvant n3-PUFA.

Project description:BackgroundNabiximols is a cannabis-based drug to treat spasticity-associated symptoms currently approved for patients with multiple sclerosis only. Cannabinoids are useful in an increasing number of medical conditions but may bear an increased risk for cardiovascular events. SativexStroke is a double-blind randomized placebo-controlled crossover monocentric clinical trial investigating the efficacy and safety of nabiximols in patients with spasticity following stroke.MethodsPatients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Cardiovascular safety was assessed before and during the trial. Primary endpoints were changes in spasticity numeric rating scale scores and electromyographic recording of the stretch reflex in affected wrist flexors. Secondary outcome measures were numeric rating scale scores for pain, sleep and bladder function, the number of daily spasms and clinical assessment of spasticity with the modified Ashworth scale. The study was registered with the EudraCT number 2016-001034-10.ResultsBetween May 2, 2018, and February 20, 2020, 41 patients entered the study. Seven patients did not complete the study, so 34 were included in the analysis. Two serious adverse events occurred, but none related to cardiovascular function. Primary and secondary efficacy outcome measures did not change from baseline during nabiximols treatment relative to placebo.ConclusionThis study suggests that nabiximols use is probably safe in stroke patients, therefore cannabinoid usefulness may be further investigated. The lack of nabiximols effect could be related to low pain levels in recruited patients or different spasticity mechanisms between post-stroke and multiple sclerosis patients. Similarly, a beneficial effect of nabiximols could have emerged if more patients with a higher level of spasticity at baseline were recruited.Clinical trial registrationhttps://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001034-10/IT.

Project description:BackgroundMulticentre trials investigating food allergies by double blind placebo controlled food challenges (DBPCFC) need standardized procedures, challenge meals and evaluation criteria. We aimed at developing a standardized approach for identifying patients with birch related soy allergy by means of DBPCFC to soy, including determination of threshold levels, in a multicentre setting.MethodsMicrobiologically stable soy challenge meals were composed of protein isolate with consistent Gly m 4 levels. Patients sensitized to main birch allergen Bet v 1 and concomitant sensitization to its soy homologue Gly m 4 underwent DBPCFC. Outcome was defined according to presence and/or absence of ten objective signs and intensity of eight subjective symptoms as measured by visual analogue scale (VAS).Results138 adult subjects (63.8% female, mean age 38 years) underwent DBPCFC. Challenge meals and defined evaluation criteria showed good applicability in all centres involved. 45.7% presented with objective signs and 65.2% with subjective symptoms at soy challenge. Placebo challenge meals elicited non-cardiovascular objective signs in 11.6%. In 82 (59.4%) subjects DBPCFC was judged as positive. 70.7% of DPBCFC+ showed objective signs and 85.4% subjective symptoms at soy challenge. Subjective symptoms to soy challenge meal in DBPCFC+ subjects started at significantly lower dose levels than objective signs (p < 0.001). Median cumulative eliciting doses for first objective signs in DBPCFC+ subjects were 4.7 g [0.7-24.7] and 0.7 g [0.2-4.7] total soy protein for first subjective symptoms (p = 0.01).ConclusionsWe present the hitherto largest group of adults with Bet v 1 and Gly m 4 sensitization being investigated by DBPCFC. In this type of food allergy evaluation of DBPCFC outcome should not only include monitoring of objective signs but also scoring of subjective symptoms. Our data may contribute to standardize DBPCFC in pollen-related food allergy in multicentre settings.Trial registrationEudraCT: 2009-011737-27.

Dataset Information

Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

Publications

Within-subject, double-blind, randomized, placebo-controlled evaluation of combining the cannabinoid dronabinol and the opioid hydromorphone in adults with chronic pain.

Similar Datasets

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