hydrocodone and Substance-Withdrawal-Syndrome

Hyperalgesia has been demonstrated to be a cardinal sign of physical withdrawal from opioids in preclinical models for more than 30 years, although few empirical data exist to support its occurrence in humans. In this preliminary study we used the acute opioid physical dependence (APD) model to test for the presence of hyperalgesia to experimental cold-pressor pain in 4 healthy non-opioid-dependent men via 3 different pretreatment opioid administration protocols previously demonstrated to induce APD (morphine 18 mg/70 kg intramuscular, morphine 10 mg/70 kg intravenous, hydromorphone 2 mg/70 kg intravenous), repeated on 2 separate occasions, and placebo. Cold-pressor pain threshold and tolerance were examined before opioid administration and 5 and 15 minutes after precipitated withdrawal with naloxone 10 mg/70 kg intravenous. Paired t tests comparing change scores between the opioid pretreatments and placebo showed that pain threshold and tolerance to the cold-pressor uniformly decreased across all APD induction methods, and the effect size was large (approximately 70% of baseline) and reproducible. These findings provide initial support for the existence of opioid-induced hyperalgesia, which has been conceptualized as a coexisting opponent process to opioid-induced analgesia and proposed to be an alternative explanation for the development of analgesic tolerance to opioids.

Topics: Acute Disease; Adult; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Hemodynamics; Humans; Hydrocodone; Hyperalgesia; Infusions, Intravenous; Male; Morphine; Naloxone; Narcotic Antagonists; Pain Measurement; Substance Withdrawal Syndrome

Prescription opioids are often used during pregnancy even though they are associated with neonatal opioid withdrawal syndrome (NOWS). Most studies of adverse outcomes of opioid use for pain have assessed only the class-wide outcome despite the pharmacodynamic and pharmacokinetic heterogeneity across opioid medications.. To compare the risk of NOWS across common types of opioids when prescribed as monotherapy during the last 3 months of pregnancy.. This cohort study analyzed administrative claims data of Medicaid-insured mothers and newborns in 46 states and Washington DC from January 1, 2000, through December 31, 2014. Participants were mothers with 2 or more dispensed opioid prescriptions within 90 days before delivery and their eligible live-born neonates. Data were analyzed from February 2020 to March 2021.. Different types of opioid medications were compared by agonist strength (strong vs weak) and half-life (medium vs short and long vs short) of the opioid active ingredient.. The primary outcome was NOWS, which was identified using an International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code in the 30 days after delivery. Relative risks (RRs) were adjusted for an exposure propensity score, including demographic characteristics, comorbidities, other medication use, and opioid treatment characteristics (including morphine milligram equivalents), using fine stratification.. The cohort comprised 48 202 opioid-exposed pregnancies with live newborns. A total of 1069 neonates (2.2%) had NOWS and 559 (1.2%) had severe NOWS. Opioid exposure during pregnancy included 16 202 pregnancies exposed to codeine, 4540 to oxycodone, 1244 to tramadol, 260 to methadone (dispensed for pain), 90 to hydromorphone, and 63 to morphine compared with 25 710 exposed to hydrocodone. Demographic characteristics varied across opioids, with tramadol, oxycodone, methadone, hydromorphone, and morphine being more commonly dispensed at older maternal age (≥35 years). Compared with hydrocodone, codeine had a lower adjusted RR of NOWS (0.57; 95% CI, 0.46-0.70), with a similar adjusted RR for tramadol (RR, 1.06; 95% CI, 0.73-1.56), and 2- to 3-fold higher adjusted RRs for oxycodone (1.87; 95% CI, 1.66-2.11), morphine (2.84; 95% CI, 1.30-6.22), methadone (3.02; 95% CI, 2.45-3.73), and hydromorphone (2.03; 95% CI, 1.09-3.78). Strong agonists were associated with a higher risk of NOWS than weak agonists (RR, 1.97; 95% CI, 1.78-2.17), and long half-life opioids were associated with an increased risk compared with short half-life products (RR, 1.33; 95% CI, 1.12-1.56). Findings were consistent across sensitivity and subgroup analyses.. Results of this study show higher risk of NOWS and severe NOWS among neonates with in utero exposure to strong agonists and long half-life prescription opioids. Information on the opioid-specific risk of NOWS may help prescribers select opioids for pain management in late stages of pregnancy.

Topics: Adult; Analgesics, Opioid; Codeine; Cohort Studies; Female; Humans; Hydrocodone; Hydromorphone; Infant, Newborn; Infant, Newborn, Diseases; Methadone; Morphine; Neonatal Abstinence Syndrome; Oxycodone; Pain; Pregnancy; Prescriptions; Substance Withdrawal Syndrome; Tramadol; United States

Illicit use of buprenorphine has increased in the U.S., but our understanding of its use remains limited. This study aims to explore Web-forum discussions about the use of buprenorphine to self-treat opioid withdrawal symptoms.. PREDOSE, a novel Semantic Web platform, was used to extract relevant posts from a Web-forum that allows free discussions on illicit drugs. First, we extract information about the total number of buprenorphine-related posts per year between 2005 and 2013. Second, PREDOSE was used to identify all posts that potentially contained discussions about buprenorphine and opioid withdrawal. A total number of 1,217 posts that contained these terms were extracted and entered into NVivo data base. A random sample of 404 (33%) posts was selected and content analyzed.. Buprenorphine-related posts increased over time, peaking in 2011. The posts were about equally divided between those that expressed positive and negative views about the effectiveness of buprenorphine in relieving withdrawal symptoms. Web-forum participants emphasized that buprenorphine's effectiveness may become compromised because of the "size of a person habit," and/or when users repeatedly switch back and forth between buprenorphine and other illicit opioids. Most posts reported use of significantly lower amounts of buprenorphine (≤2 mg) than doses used in standard treatment. Concomitant use of other psychoactive substances was also commonly reported, which may present significant health risks.. Our findings highlight the usefulness of Web-based data in drug abuse research and add new information about lay beliefs about buprenorphine that may help inform prevention and policy measures.

Topics: Adult; Attitude to Health; Buprenorphine, Naloxone Drug Combination; Cross-Sectional Studies; Female; Health Surveys; Humans; Hydrocodone; Internet; Middle Aged; Opioid-Related Disorders; Oxycodone; Self Medication; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Adolescent; Adolescent Behavior; Behavior Therapy; Buprenorphine; Humans; Hydrocodone; Naltrexone; Opioid-Related Disorders; Patient Compliance; Substance Withdrawal Syndrome; Treatment Outcome; United States

Topics: Alprazolam; Benzodiazepines; Drug Administration Schedule; Female; Humans; Hydrocodone; Methadone; Middle Aged; Opioid-Related Disorders; Psychoses, Substance-Induced; Substance Withdrawal Syndrome; Time Factors

A series of 8-alkyl-3-methoxy-17-methylmorphinan-6-ones (3C) and -isomorphinan-6-ones (3T) were prepared by conjugate addition of lithium dialkylcuprates to the corresponding 7,8-didehydro-6-ones 2C and 2T. These 17-methyl compounds were potent analgesics and were converted to mixed narcotic agonists-antagonists 7-10, by replacement of the 17-methyl groups with cycloalkylmethyl moieties. The 8 substituent modified the type of activity observed. One of these compounds, 17-(cyclobutylmethyl)-3-hydroxy-8 beta-methylmorphinan-6-one (10Ca), had an agonist-antagonist ratio of 0.1. Compound 10Ca did not support or cause dependence in rats. This compound, however, appeared to be a typical narcotic agent in morphine-dependent monkeys.

Topics: Acetates; Analgesics; Animals; Haplorhini; Humans; Mice; Morphinans; Morphine Dependence; Narcotic Antagonists; Rats; Reaction Time; Structure-Activity Relationship; Substance Withdrawal Syndrome; Substance-Related Disorders

3,6-Dimethoxy-7 beta, 17-dimethyl-4-hydroxy-5,6,8,14-tetradehydromorphinan (2) was converted to the 4-deoxy compound 4 and hydrolyzed to a mixture of the B/C-cis (C series) and B/C-trans (T series) isomers of 7,8-didehydromorphinan-6-one, 5. Hydrogenation of the separated isomers gave 7-methyl-6-oxo derivatives 6a. 7,8-Dimethyl-(6b) or 7-methyl-8-ethylmorphinan-6-one (6c) was prepared by reaction of 5 with lithium organocuprates. The analgesic N-methyl compounds 6 were converted to 17-(cyclopropylmethyl) or 17-(cyclobutylmethyl) derivatives 10--13. Some of these compounds had mixed profiles of narcotic agonist-antagonist effects. Studies with drug-dependent monkeys indicated that several of these compounds with an analgesic-antagonist ratio of less than 0.4 substitute for morphine.

Topics: Analgesics; Animals; Chemical Phenomena; Chemistry; Humans; Morphinans; Morphine Dependence; Narcotic Antagonists; Substance Withdrawal Syndrome