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Very low dose naltrexone in opioid detoxification: a double-blind, randomized clinical trial of efficacy and safety.

ABSTRACT: Withdrawal syndrome is one of the initial focuses of opioid detoxification. Very low dose naltrexone (VLNTX) has been found to reduce opioid tolerance and dependence in animal and human clinical studies. The aim of this study was to determine the safety and efficacy of VLNTX during early stages of detoxification. In a multi-arm parallel, double-blind, randomized controlled trial, 63 opioid-dependent male participants referring to Imam Reza Rehabilitation Center were allocated to three equal groups using block randomization method. They received 0.125 mg, 0.250 mg of VLNTX or placebo daily for 10 days, together with the routine clonidine-based protocol. Self-reported and observer ratings of withdrawal severity and adverse events were measured on the 1st, 4th and 10th day of treatment. Runny eyes (p?=?0.006), anxiety (p?=?0.031) and dehydration (p?=?0.014) were reduced during the whole 10 days in the 0.125 mg VLNTX-treated group compared to placebo. Only drowsiness (p?=?0.043) and dysphoric mood (p?

SUBMITTER: Afshari R

PROVIDER: S-EPMC6990297 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Very low dose naltrexone in opioid detoxification: a double-blind, randomized clinical trial of efficacy and safety.

Afshari Reza R Khadem-Rezaiyan Majid M Khatibi Moghadam Hoda H Talebi Mahdi M

Toxicological research 20191121 1

Withdrawal syndrome is one of the initial focuses of opioid detoxification. Very low dose naltrexone (VLNTX) has been found to reduce opioid tolerance and dependence in animal and human clinical studies. The aim of this study was to determine the safety and efficacy of VLNTX during early stages of detoxification. In a multi-arm parallel, double-blind, randomized controlled trial, 63 opioid-dependent male participants referring to Imam Reza Rehabilitation Center were allocated to three equal grou ...[more]

PMID: 32042711

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Project description:BackgroundLow-dose naltrexone (LDN) is used widely as an off-label treatment for pain despite limited evidence for its effectiveness. A few small trials with a high risk of bias have investigated the effect of LDN on pain associated with fibromyalgia in women, but larger and more methodologically robust studies are needed. The primary aim of this randomized controlled trial is to investigate if 12 weeks of LDN treatment is superior to placebo in reducing the average pain intensity during the last 7 days in women with fibromyalgia.MethodsA single-center, permuted block randomized, double-blind, placebo-controlled, parallel-group trial will be performed in Denmark. Randomization comprises 100 women aged 18-64 years diagnosed with fibromyalgia who will be treated with either LDN or placebo for 12 weeks including a 4-week titration phase. The primary outcome is change in average pain intensity (during the last 7 days) from baseline to 12 weeks. Secondary outcomes are other fibromyalgia-related symptoms, i.e., tenderness, fatigue, sleep disturbance, stiffness, memory problems, depression, anxiety and measures of global assessment, physical function, impact of fibromyalgia, pain distribution, and health-related quality of life. Intention-to-treat analysis will be performed, and the number of responders with a more than 15%, 30%, and 50% improvement of pain after 12 weeks will be calculated for the LDN and placebo groups. Exploratory outcomes include measures of pain sensitivity, muscle performance, and biomarkers.DiscussionThis study will contribute with high-level evidence on the efficacy of low-dose naltrexone for the treatment of pain in women with fibromyalgia. Secondary outcomes include both disease-specific and generic components investigating whether LDN influences other symptoms than pain. Explorative outcomes are included to provide greater insight into the mechanism of action of LDN and possibly a better understanding of the underlying pathology in fibromyalgia.Trial registrationEudraCT 2019-000702-30. Registered on 12 July 2019. ClinicalTrials.gov NCT04270877. Registered on 17 February 2020.

Project description:Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive impairments. Naltrexone is a competitive antagonist of opioid receptors commonly used to treat opioid addiction; its oral use against agonists side effects is limited by the decrease of opioids-therapeutic efficacy and own adverse effects. The intranasal delivery of naltrexone could offer a quick and effective achievement of CNS based on extracellular mechanisms including perineural and perivascular transport. The aim of the study was to test the efficacy of intranasal low-dose naltrexone in reducing intraperitoneal morphine and oxycodone side effects in rodents. In mice, 1 μg naltrexone intranasally administered 30 min before opioids reduced cognitive impairments and motor alteration induced by 10 mg kg-1 morphine and 60 mg kg-1 oxycodone in the Passive avoidance and Rota rod tests, respectively. Moreover, naltrexone rebalanced opioid-induced reduction of the intestinal transit and latency of feces expulsion as well as food intake inhibition. Importantly, 1 μg naltrexone instillation did not block analgesia as demonstrated by the Hot plate test. In rats, intranasal naltrexone counteracted the opioid-induced pica phenomenon related to emesis and increased water and palatable food intake. The effects were comparable to that achieved by metoclopramide used as reference drug. Treatments did not influence body weight. Lastly, the safety of the intranasal delivery has been checked by hematoxylin-eosin staining that did not show histological alterations of the nasal cavity. In conclusion, intranasal low-dose naltrexone counteracted morphine and oxycodone induced gastrointestinal and CNS side effects without impairing opioid analgesia. It is a candidate to be a valid clinical strategy deserving deep analysis.

Project description:Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD). We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH. Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ² = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ² = 0.22, P = .64) of SODAS-MPH treatment. Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential. ClinicalTrials.gov identifier: NCT01673594.

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Very low dose naltrexone in opioid detoxification: a double-blind, randomized clinical trial of efficacy and safety.

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Very low dose naltrexone in opioid detoxification: a double-blind, randomized clinical trial of efficacy and safety.

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