Treatment Of Opiate Withdrawal Research Articles

Current management of neonatal abstinence syndrome: a survey of practice in the UK and Ireland

ObjectiveTo study the current management practices of neonatal abstinence syndrome (NAS) throughout the UK and Ireland and identify changes in practice from the most recent survey in 2008.DesignPostal questionnaire to...

Mitragyna speciosa: Opioid Addiction Treatment and Risk of Use

<p>Kratom (<em>Mitragyna speciosa</em> (Korth.) Havil.) is a plant that originated from the rainforest in Southeast Asia, mainly grows in Thailand, Malaysia, and Indonesia. Kratom has been used traditionally as an herbal remedy for the treatment of various illnesses. Kratom gained notoriety due to its potential as an analgesic, opiate withdrawal treatment, anxiolytic, antidepressant, and antidiabetic with an unclear risk of addiction and toxicity fueled by a false sense of security due to its identity as a member of the coffee family. This article is a narrative review on kratom to highlight its pharmacological and toxicological properties, and the analytical method of Kratom, especially its potential as an opioid withdrawal therapy and its risk of abuse.</p>

Oleoyl alanine (HU595): a stable monomethylated oleoyl glycine interferes with acute naloxone precipitated morphine withdrawal in male rats.

Oleoyl glycine, a little studied fatty acid amide similar in structure to anandamide, interferes with nicotine addiction in mice and acute naloxone-precipitated morphine withdrawal (MWD) in rats. Because endogenous oleoyl glycine is subject to rapid enzymatic deactivation, we evaluated the potential of more stable analogs to interfere with opiate withdrawal. The potential of monomethylated oleoyl glycine (oleoyl alanine, HU595) to interfere with somatic and aversive effects of acute naloxone-precipitated MWD, its duration, and mechanism of action was assessed in male Sprague Dawley rats. The potential of dimethylated oleoyl glycine (HU596) to interfere with the aversive effects of naloxone-precipitated MWD was also investigated. Oleoyl alanine (HU595) interfered with somatic and aversive effects produced by naloxone-precipitated MWD at equivalent doses (1 and 5mg/kg, i.p.) as we have reported for oleoyl glycine; however, oleoyl alanine produced a longer lasting (60min) interference, yet did not produce rewarding or aversive effects on its own and did not modify locomotor activity. HU596 was not effective. The interference with aversive effects of naloxone-precipitated MWD by oleoyl alanine was prevented by both a PPARα antagonist and a CB1 receptor antagonist. Accordingly, the compound was found to inhibit FAAH and activate PPARα in vitro. Finally, oleoyl alanine also reduced acute naloxone-precipitated MWD anhedonia, as measured by decreased saccharin preference. Oleoyl alanine (also an endogenous fatty acid) may be a more stable and effective treatment for opiate withdrawal than oleoyl glycine.

Mitragynine Attenuates Morphine Withdrawal Effects in Rats-A Comparison With Methadone and Buprenorphine.

BackgroundOpiate addiction is a major health problem in many countries. A crucial component of the medical treatment is the management of highly aversive opiate withdrawal signs, which may otherwise lead to resumption of drug taking. In a medication-assisted treatment (MAT), methadone and buprenorphine have been implemented as substitution drugs. Despite MAT effectiveness, there are still limitations and side effects of using methadone and buprenorphine. Thus, other alternative therapies with less side effects, overdosing, and co-morbidities are desired. One of the potential pharmacotherapies may involve kratom's major indole alkaloid, mitragynine, since kratom (Mitragyna speciosa Korth.) preparations have been reported to alleviate opiate withdrawal signs in self-treatment in Malaysian opiate addicts.MethodsBased on the morphine withdrawal model, rats were morphine treated with increasing doses from 10 to 50 mg/kg twice daily over a period of 6 days. The treatment was discontinued on day 7 in order to induce a spontaneous morphine abstinence. The withdrawal signs were measured daily after 24 h of the last morphine administration over a period of 28 abstinence days. In rats that developed withdrawal signs, a drug replacement treatment was given using mitragynine, methadone, or buprenorphine and the global withdrawal score was evaluated.ResultsThe morphine withdrawal model induced profound withdrawal signs for 16 days. Mitragynine (5–30 mg/kg; i.p.) was able to attenuate acute withdrawal signs in morphine dependent rats. On the other hand, smaller doses of methadone (0.5–2 mg/kg; i.p.) and buprenorphine (0.4–1.6 mg/kg; i.p.) were necessary to mitigate these effects.ConclusionsThese data suggest that mitragynine may be a potential drug candidate for opiate withdrawal treatment.

Gabapentin, Pregabalin, and Placebo in Reducing Opioid Withdrawal Symptoms in Opioid-dependent Individuals: A Randomized-controlled Trial

Objective: The objective of this study was to compare the efficacy of pregabalin and gabapentin in patients undergoing outpatient treatment for opiate withdrawal. Materials and Methods: In a 4-week double-blinded, randomized, placebo-controlled trial of pregabalin and gabapentin in buprenorphine-assisted detoxification (BAD) in the Specialized Addictive Behaviors Unit, an outpatient unit for the treatment of patients with an addictive disorder serving the city of Isfahan (Iran), 50 outpatients, 45 male individuals and 5 female individuals, aged 20 to 60 years, who met DSM-V criteria for opiate dependence, were randomly assigned to receive adjunctive treatment with either pregabalin (450 mg/d), gabapentin (1600 mg/d), or placebo under double-blinded conditions. The severity of subjective withdrawal symptoms were measured using the Short Opioid Withdrawal Scale (SOWS) at 5 stages. Results: Despite the effect of pregabalin and gabapentin on controlling some of the withdrawal symptoms, no significant differences were reported among the 3 groups. Conclusions: Dosages of 450 mg/d of pregabalin and 1600 mg/d of gabapentin are not significantly superior to placebo in controlling opiate withdrawal symptoms.

Detoxification from methadone using low, repeated, and increasing doses of ibogaine: A case report

Background and aimsIbogaine is a natural alkaloid that has been used in the last decades as an adjuvant for the treatment of opiate withdrawal. Despite the beneficial results suggested by animal studies and case series, there is a lack of clinical trials to assess the safety and efficacy of ibogaine. Moreover, the majority of reports described cases of heroin-dependent individuals, with and without concomitant use of methadone, using high doses of ibogaine. Therefore, it is not clear if ibogaine at low doses could be used therapeutically in people on methadone maintenance treatments (MMT).MethodsCase report of a female on MMT for 17 years who performed a self-treatment with several low and cumulative doses of ibogaine over a 6-week period.ResultsThe patient successfully eliminated her withdrawals from methadone with ibogaine. Each administration of ibogaine attenuated the withdrawal symptoms for several hours, and reduced the tolerance to methadone until all signs of withdrawal symptoms disappeared at the...

Standard Care for Neonatal Opiate Withdrawal Treatment

To standardize care that is provided to newborns who are experiencing symptoms of neonatal opiate withdrawal (NOW) by instituting inter-rater reliability training for all nursing staff and implementing a standardized medical protocol. To change the nursing assessment practice of NOW symptoms from the use of an individual, subjective assessment to the use of the standardized Finnegan Scoring Tool using inter-rater reliability. The previous Morphine treatment protocol will be replaced by a Methadone or Subutex treatment protocol based on the fetal in-utero drug exposure. The inter-rater reliability training will occur in an 8-hour class required of all nursing staff. Additionally, each nurse will be observed by a inter-rater reliability trainer for three NOW scorings. The medical director created and implemented a protocol for the distribution of methadone and also created and implemented a protocol for the use of subutex in newborn. We are also currently investigating the use of phenobarbital and clonidine as adjunct treatments. A 50-item database has been created to look at various factors affecting newborns experiencing opiate withdrawal. The first outcome to be evaluated by nursing staff will be early recognition, reliable scoring, and standardized implementation of nonpharmacologic interventions for newborns demonstrating the NOW symptoms. The second outcome to be evaluated will be length of treatment and length of stay for the medical protocols. Nurses are actively participating in creating and establishing the evidence to standardized care that will improve outcomes for newborns experiencing NOW symptoms and for the families who are caring for these newborns.

Behavioural and Neurochemical Assessment of Heantos 4 on Preclinical Models of Morphine-Dependence

Objective: Opiate addiction is characterized by compulsive drug use and severe withdrawal symptoms during abstinence. Heantos 4, an herbal pharmacotherapy recently approved for opiate withdrawal treatment in Vietnam, has shown anti-craving properties. The present study is the first preclinical assessment of the effects of Heantos 4 on opiate withdrawal and the rewarding properties of morphine, along with its action on a critical neural substrate of addiction, the mesolimbic dopamine (DA) system. Methods: Rats received morphine treatments (10 mg/kg, i.p.) for seven days. On Day 8, Heantos 4 (100, 250 or 500 mg/kg, p.o.) was administered prior to naloxone (1 or 10 mg/kg, i.p.). Affective withdrawal symptoms were measured using conditioned place aversion (CPA) and somatic withdrawal symptoms were scored separately. The effect of Heantos 4 on morphine-induced (5 mg/kg, i.p.) conditioned place preference (CPP) was assessed by administering it prior to conditioning, expression or morphine-induced reinstatement. Additionally, the effect of Heantos 4 on the long-term maintenance of morphine-induced CPP was assessed bi-weekly for 6 weeks. Microdialysis studies assessed DA efflux in the nucleus accumbens of rats receiving one or seven repeated treatments of Heantos 4 (500 mg/kg, p.o.) and morphine, or receiving Heantos 4 and naloxone (10 mg/kg, i.p.). Results: Heantos 4 reduced somatic but not affective components of naloxone-precipitated opiate withdrawal. It attenuated acquisition but not expression or reinstatement of morphine-induced CPP. Long-term maintenance of morphine-induced CPP was also reduced. Heantos 4 by itself enhanced DA efflux but blunted morphine-evoked DA release on Day 1 and 7. Heantos 4 attenuated naloxone-induced decrease in DA in morphine-dependent rats. Conclusion: These findings demonstrate that Heantos 4 alleviates symptoms of somatic opiate withdrawal and indicate potential effects on incentive motivation. Moreover, Heantos 4 may modulate DA transmission that limits or antagonizes non-physiological fluctuations in mesolimbic DA activity induced by morphine and naloxone.

Tramadol vs. Buprenorphine for the Treatment of Opioid Dependence: A Comparative Study

Background: Tramadol is an atypical centrally acting synthetic analgesic and its o-demethylated metabolite, (+)-o-demethyltramadol (known as m1), has greater affinity for the mu-opioid receptor which makes it a candidate for opiate withdrawal treatment. , it appears to have low abuse potential and is a non-scheduled analgesic. Aim and Objective: to compare the effects and relative clinical utility of Tramadol and Buprenorphine in the treatment of heroine withdrawal in opioid dependant patients. Methods: Ina randomized open label parallel group design study, 70 patients with opioid dependence with daily heroine use equal to 1-10 mg, 10-20 mg, >20 mg methadone using stratified proportionate sampling were assigned into two treatment groups i.e. Tramadol and Buprenorphine. Flexible dosing schedule was followed and drug was titrated using (COWS) Clinical Opiate Withdrawal Scale and (CGI) Clinical Global Impression Results: There was statistically significant difference between the two groups in patients with moderate level of addiction with 78% of Tramadol group and 57% of the Buprenorphine group completed detoxification at the end of 12 weeks. Whereas patients with severe level of addiction had to be maintained on buprenorphine and detoxification could not be completed with high dropout rate in tramadol group Discussion: Tramadol has good efficacy in detoxification and relapse prevention in patients with moderate level of opioid dependence as compared to buprenorphine, Whereas Buprenorphine is better for maintenance treatment and is of higher clinical utility in severe level of opioid dependence where maintenance therapy is required.

Role of Medication and Background Variables in Dropout from Opiate Withdrawal Treatment – A Retrospective Chart Review

The present study aimed to examine whether retention in inpatient opiate detoxification was affected by the introduction of buprenorphine as a standard medication in opiate withdrawal, compared to older substances, when controlling for previous dropouts from detoxification, age, gender and current aftercare treatment planning. This chart review with a naturalistic design studied all inpatient opiate detoxifications in a detoxification unit during five years. In total, 375 patients with a total of 639 detoxification episodes were studied, with the withdrawal medication prescribed being buprenorphine, clonidine, dextropropoxyphene or methadone. In logistic regression, using buprenorphine as reference, completion of detoxification was unrelated to the choice of medication, but associated with the presence of an aftercare plan upon admission, older age and a lower number of previous dropouts. However, dropouts remained significantly longer until dropout with buprenorphine, compared to clonidine and dextropropoxyphene. While the longer time to dropout suggests a higher effectiveness in withdrawal treatment with buprenorphine, no overall effect was seen on actual dropout rates. Lack of an aftercare plan and previous dropouts may be risk factors of dropout in opiate detoxification.

Methadone at tapered doses for the management of opioid withdrawal.

The evidence of tapered methadone's efficacy in managing opioid withdrawal has been systematically evaluated in the previous version of this review that needs to be updated To evaluate the effectiveness of tapered methadone compared with other detoxification treatments and placebo in managing opioid withdrawal on completion of detoxification and relapse rate. We searched: Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 4), PubMed (January 1966 to May 2012), EMBASE (January 1988 to May 2012), CINAHL (2003- December 2007), PsycINFO (January 1985 to December 2004), reference lists of articles. All randomised controlled trials that focused on the use of tapered methadone versus all other pharmacological detoxification treatments or placebo for the treatment of opiate withdrawal. Two review authors assessed the included studies. Any doubts about how to rate the studies were resolved by discussion with a third review author. Study quality was assessed according to the criteria indicated in the Cochrane Handbook for Systematic Reviews of Interventions. Twenty-three trials involving 2467 people were included. Comparing methadone versus any other pharmacological treatment, we observed no clinical difference between the two treatments in terms of completion of treatment, 16 studies 1381 participants, risk ratio (RR) 1.08 (95% confidence interval (CI) 0.97 to 1.21); number of participants abstinent at follow-up, three studies, 386 participants RR 0.98 (95% CI 0.70 to 1.37); degree of discomfort for withdrawal symptoms and adverse events, although it was impossible to pool data for the last two outcomes. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (eight studies), anxiolytic (two studies), paiduyangsheng (one study). Comparing methadone with placebo (two studies) more severe withdrawal and more drop-outs were found in the placebo group. The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long- acting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.

Reduced Methadone Clearance During Aromatase Inhibition

Methadone is increasingly used in pain management and is a cornerstone in the treatment of opiate withdrawal. It is subject to highly variable clearance among patients. The complete metabolic disposition of methadone is likely to involve a number of enzymes, including specifically CYP2B6. Previous studies in vitro suggest that metabolism by aromatase may also contribute. Single-dose methadone pharmacokinetics (2 mg, intravenous) were studied in 15 healthy postmenopausal women in the presence and absence of a potent aromatase inhibitor, letrozole. A sequential design was used, involving a control period followed by treatment with letrozole (2.5 mg/d, 11 days), in which each subject served as her own control. On average, letrozole treatment reduced methadone systemic clearance by 22% (P = 0.001), increased methadone AUC by 23% (P = 0.007), and increased elimination half-life by 21% (P = 0.042). The plasma parent-to-metabolite ratio also increased (P = 0.009), and there was a linear relationship (R2 = 0.74) between change in this plasma ratio and change in methadone AUC0-∞. In contrast, there was no such association with change in apparent urinary methadone clearance. Letrozole did not change methadone distribution half-life or its volume of distribution. Overall, these data demonstrate a significant decrease in methadone clearance during coadministration of letrozole, consistent with decreased metabolism brought about by aromatase inhibition. An involvement of aromatase in the disposition of methadone may help explain the difficulty in methadone dosing and suggests a broader role for this catalyst of endogenous steroid metabolism in xenobiotic drug disposition.

The Mechanistic Basis for Noncompetitive Ibogaine Inhibition of Serotonin and Dopamine Transporters

Ibogaine, a hallucinogenic alkaloid proposed as a treatment for opiate withdrawal, has been shown to inhibit serotonin transporter (SERT) noncompetitively, in contrast to all other known inhibitors, which are competitive with substrate. Ibogaine binding to SERT increases accessibility in the permeation pathway connecting the substrate-binding site with the cytoplasm. Because of the structural similarity between ibogaine and serotonin, it had been suggested that ibogaine binds to the substrate site of SERT. The results presented here show that ibogaine binds to a distinct site, accessible from the cell exterior, to inhibit both serotonin transport and serotonin-induced ionic currents. Ibogaine noncompetitively inhibited transport by both SERT and the homologous dopamine transporter (DAT). Ibogaine blocked substrate-induced currents also in DAT and increased accessibility of the DAT cytoplasmic permeation pathway. When present on the cell exterior, ibogaine inhibited SERT substrate-induced currents, but not when it was introduced into the cytoplasm through the patch electrode. Similar to noncompetitive transport inhibition, the current block was not reversed by increasing substrate concentration. The kinetics of inhibitor binding and dissociation, as determined by their effect on SERT currents, indicated that ibogaine does not inhibit by forming a long-lived complex with SERT, but rather binds directly to the transporter in an inward-open conformation. A kinetic model for transport describing the noncompetitive action of ibogaine and the competitive action of cocaine accounts well for the results of the present study.

Tramadol versus Methadone for Treatment of Opiate Withdrawal: A Double-Blind, Randomized, Clinical Trial

The aim of this study was to compare the efficacy and safety of tramadol versus methadone for treatment of opiate withdrawal. Seventy patients randomly were assigned in two groups to receive either prescribed methadone (60 mg/day) or tramadol (600 mg/day). The withdrawal syndrome of patients was evaluated before and after rapid opiate detoxification using the Objective Opioid Withdrawal Scale (OOWS). No significant differences existed in overall OOWS scores between two groups (P = 0.11). Dropout rates were similar in both groups. Side effects in the tramadol group were as or less common than in the methadone group, with the exception of perspiration. Tramadol may be as effective as methadone in the control of withdrawal and could be considered as a potential substitute for methadone to manage opioids withdrawal.

Implicit and Explicit Cognition of Chinese Heroin Abusers

Sixty-five heroin abusers receiving Methadone Maintenance Treatment (MMT), 38 heroin abusers not receiving MMT, and 30 nonusers of drugs participated in this investigation of cognition in heroin and methadone users. Heroin users were measured for both implicit and explicit cognition, while the control group of nonusers was measured only for implicit cognition. The results demonstrate that implicit cognition can influence the development of addictive behaviors, and that implicit and explicit cognition of heroin were separate and independent constructs. Based on the results of Implicit Association Tests (IAT; Greenwald, McGhee, & Schwartz, 1998) MMT appears to be a valid method for opiate withdrawal treatment as it reverses the implicit desire for heroin in heroin abusers.

Opiate treatment for opiate withdrawal in newborn infants

Neonatal abstinence syndrome (NAS) due to opiate withdrawal may result in disruption of the mother-infant relationship, sleep-wake abnormalities, feeding difficulties, weight loss and seizures. To assess the effectiveness and safety of using an opiate compared to a sedative or non-pharmacological treatment for treatment of NAS due to withdrawal from opiates. The review was updated in 2010 with additional searches CENTRAL, MEDLINE and EMBASE supplemented by searches of conference abstracts and citation lists of published articles. Randomized or quasi-randomized controlled trials of opiate treatment in infants with NAS born to mothers with opiate dependence. Each author assessed study quality and extracted data independently. Nine studies enrolling 645 infants met inclusion criteria. There were substantial methodological concerns in all studies comparing an opiate with a sedative. Two small studies comparing different opiates were of good methodology.Opiate (morphine) versus supportive care (one study): A reduction in time to regain birth weight and duration of supportive care and a significant increase in hospital stay was noted.Opiate versus phenobarbitone (four studies): Meta-analysis found no significant difference in treatment failure. One study reported opiate treatment resulted in a significant reduction in treatment failure in infants of mothers using only opiates. One study reported a significant reduction in days treatment and admission to the nursery for infants receiving morphine. One study reported a reduction in seizures, of borderline statistical significance, with the use of opiate.Opiate versus diazepam (two studies): Meta-analysis found a significant reduction in treatment failure with the use of opiate.Different opiates (six studies): there is insufficient data to determine safety or efficacy of any specific opiate compared to another opiate. Opiates compared to supportive care may reduce time to regain birth weight and duration of supportive care but increase duration of hospital stay. When compared to phenobarbitone, opiates may reduce the incidence of seizures but there is no evidence of effect on treatment failure. One study reported a reduction in duration of treatment and nursery admission for infants on morphine. Compared to diazepam, opiates reduce the incidence of treatment failure. A post-hoc analysis generates the hypothesis that initial opiate treatment may be restricted to infants of mothers who used opiates only. In view of the methodologic limitations of the included studies the conclusions of this review should be treated with caution.

Acetyl-L-Carnitine in the Management of Pain During Methadone Withdrawal Syndrome

This study was designed to determine the short-term effect of acetyl-l-carnitine (ALC) on symptoms of withdrawal in opiate-dependent subjects and animals and, in particular, on pain, given the efficacy of ALC in other typologies of pain. The study consists of 2 branches: a clinical study and a preclinical one, both with a randomized placebo-controlled design. Thirty subjects meeting clinical criteria for methadone dependence were consecutively recruited and treated with ALC 2 g/d or placebo for a 3-week detoxification period. Withdrawal symptoms and pain were evaluated through the Short Opiate Withdrawal Syndrome scale, and the Huskisson's analogue scale for pain. In the preclinical study, mice previously received a pretreatment (saline solution or morphine), and subsequently, each group was randomly divided in 4 subgroups that received a treatment of saline, methadone, ALC, or amitriptyline, respectively. Hot plate test and Writhing test were used to evaluate pain intensity. Average Short Opiate Withdrawal Syndrome total scores during the first 5 days of treatment resulted significantly higher in controls than in the ALC group (P < 0.05). Pain scores in the Huskisson's analogue scale were considerably lower in the group of patients taking ALC than in the control group after 1 week of ALC treatment until the end of the study. Results of the preclinical study show that the administration of methadone for 7 days in morphine-tolerant mice did not produce any modification of the pain threshold. By contrast, the 7-day coadministration of methadone and ALC in morphine-tolerant mice induced an analgesic effect evaluated 3 hours after the last injection. Acetyl-L-carnitine acted as an effective antihyperalgesic agent for relieving opiate-withdrawal hyperalgesia in animals and displayed clinical efficacy on other withdrawal symptoms such as muscular tension, muscular cramps, and insomnia. Considering its tolerability, the excellent side effect profile, the absence of significant interactions, and the lack of abuse potential, ALC can be considered as a useful pharmacological adjunct in the treatment of opiate withdrawal.

Sublingual Buprenorphine for Treatment of Neonatal Abstinence Syndrome: A Randomized Trial

In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered. We conducted a randomized, open-label, active-control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to receive sublingual buprenorphine 13.2 to 39.0 mug/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system. Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/mL, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in the buprenorphine group. Treatment with buprenorphine was well tolerated. Buprenorphine administered via the sublingual route is feasible and apparently safe and may represent a novel treatment for neonatal abstinence syndrome.

Effect of add‐on gabapentin on opioid withdrawal symptoms in opium‐dependent patients

Evaluation of the efficacy of gabapentin in patients undergoing out-patient treatment for opiate withdrawal. A 3-week double-blind, randomized, placebo-controlled trial of adjunctive gabapentin in methadone-assisted detoxification (MAD). Specialized Addictive Behaviors Unit, an out-patient unit for the treatment of patients with an addictive disorder serving the city of Isfahan (Iran). Forty out-patients, 37 males and three females, aged 21-61 years, who met DSM-IV criteria for opiate dependence. Random assignment of subjects to receive adjunctive treatment with either gabapentin (900 mg/day) or placebo under double-blind conditions. Severity of subjective withdrawal symptoms using the Subjective Opiate Withdrawal Scale at six stages. Despite the superiority of gabapentin on controlling some of withdrawal symptoms, no significant differences were reported between two groups. Dosage of 900 mg/day of gabapentin is not significantly superior to placebo in controlling opiate withdrawal symptoms.

Effects of the NMDA receptor antagonist memantine on the expression and development of acute opiate dependence as assessed by withdrawal-potentiated startle and hyperalgesia

While the N-methyl-D: -aspartate (NMDA) glutamate receptor has been strongly implicated in chronic opiate dependence, relatively few studies have examined the effects of NMDA receptor antagonists on withdrawal from acute opiate exposure. The current study examined the effects of memantine, a well-tolerated NMDA receptor antagonist, on acute opiate dependence as assessed by elevations in rodent startle responding (i.e., "withdrawal-potentiated startle") and increased pain sensitivity (i.e., hyperalgesia). Administration of memantine either attenuated (5 mg/kg) or blocked (10 mg/kg) the expression of withdrawal-potentiated startle during naloxone (2.5 mg/kg)-precipitated withdrawal from a single dose of morphine sulfate (10 mg/kg). Pre-treatment with the NMDA receptor antagonist also inhibited the exacerbation of withdrawal-potentiated startle across repeated acute opiate exposures. Memantine blocked the expression of acute dependence, but was less effective in inhibiting its escalation, when hyperalgesia was used as a measure of withdrawal. These doses of memantine did not affect startle responding or nociception in otherwise drug-free animals. Data from additional control groups indicated that the effects of memantine on the expression of withdrawal were not influenced by nonspecific interactions between the NMDA antagonist and either morphine or naloxone. These findings suggest that the NMDA receptor may play a key role in the earliest stages of opiate dependence and provide further evidence that memantine may be useful for the treatment of opiate withdrawal.