Opiate Withdrawal Symptoms Research Articles

A Comparative Clinical Study on Efficacy of Ahiphenmochanadi Vati and Sameeragaja Kesari Rasa in Opiate Withdrawal Symptoms

ABSTRACT Background: Ahiphen Vyasan (opium and its derivatives addicts) is a common addiction in Rajasthan, Punjab, and Haryana. The main symptoms of opiate withdrawal are Nadimandata (resting pulse rate), Swed Pravrutti (sweating), Arti (restlessness), Netratarak Vispharana (dialeted pupil size), Asthi or Sandhi Shoola (bone and joint pain), Nasasrava or Ashrusrava (running nose or tearing), Agnibaishamya (gastrointestinal upset), Kampa (Tramor), Jrimbha (Yawning), Vishada (feeling of unhappiness – depression), and Romanch (horripilation). Kuchla (Strychnos nux-vomica) has been mentioned as antidote for opium. Aim and Objective: The intention or aim here is to combat the opiate withdrawal effects by using opium in tapering method along with S. nux-vomica. For which the study refers to evaluate the efficacy of Ahiphenmochnadi Vati and Sameer Gaja Kesari Rasa in opium withdrawal symptoms. Material and Method: Open-labeled randomized clinical trial of thirty patients of either sex. Intervention: Group A (15 patients) was given Ahiphenmochnadi Vati, whereas Group B (15 patients) treated with Sameer Gaja Kesari Rasa. Duration: 1 month. Intragroup comparison of group A and Group B were found statistically extremely significant. Result: Intergroup comparison of Group A and B were found statistically significant. Conclusion: The present study supports the use of Ahiphenmochnadi Vati and Sameer Gaja Kesari Rasa in treating Ahiphen Vyasan with good acceptance by all treated patients.

Psychometric Characteristics of the Persian Version of the Opiate Dosage Adequacy Scale (ODAS).

The opiate dosage adequacy scale (ODAS) is one of the most common assessment tools in studies on substance use disorders, which evaluates the "adequacy" of opiate medication doses in individuals recruited in maintenance approaches. There is no investigation on the Persian version of this questionnaire in Iran. This research validated a Persian version of the ODAS. The Persian version of the ODAS was translated and revised based on the original scale presented by González-Saiz et al. The psychometric characteristics of the ODAS were assessed via direct interviews. Three trained interviewers questioned 250 patients treated in methadone maintenance clinics in Mazandaran Province (Northern Iran) for more than three months. Internal consistency and factor analysis were conducted using SPSS software, version 24. The internal consistency of ODAS was satisfactory (Cronbach's α=0.81). Across all items, considerable inter-rater reliability was discovered (kappa values between 0.90 and 1). A four-component structure was produced by the factor analysis that accounted for 77.5% of the total variance. Cronbach's α coefficients of the four components of Heroin craving and overmedication, Consumption, objective opiate withdrawal symptoms, and subjective opiate withdrawal symptoms were 0.84, 0.91, 0.83, and 0.74, respectively. The reliability and validity of the Persian version of the ODAS were satisfactory in a sample of methadone maintenance subjects. The opiate dosage adequacy scale (ODAS) is a clinical tool for measuring the adequacy of methadone dosesThe Persian version of ODAS has good validity, internal consistency, and inter-rater reliability;The Persian version of the ODAS, as a valid and reliable tool, can be used for the Iranian people under methadone maintenance. In Iran, opioids are among the most common forms of illicit drugs. In opioid maintenance programs, the adequacy of methadone doses has an important effect on treatment outcomes. Clinicians typically assess the adequacy of doses based on the patient's response to the medication. Different tools are used in clinical studies to evaluate it. One of these tools is the ODAS, developed by González-Saiz et al. In the present study, we validated the Persian version of the ODAS for Iranian patients receiving methadone maintenance programs. The results confirmed the four-factor structure of the Persian ODAS and showed its good internal consistency and inter-rater reliability.

Prospective Study of Masimo NSS-2 BRIDGE; as a Non-Pharmacological Treatment for Acute Opioid Withdrawal Symptoms

PurposeOpioids are commonly employed for treatment of acute and chronic pain. However, continued opioid use can lead to opioid use disorder. Opioid withdrawal symptoms can be severe, and avoidance of the discomfort is a key barrier to voluntary discontinuation. The NSS-2 BRIDGE™ (Masimo Corporation, Irvine, CA) is a percutaneous nerve field stimulator that can decrease symptoms of acute opiate withdrawal. The device fits behind the ear and stimulates branches of Cranial Nerves V, VII, IX, X, and periauricular occipital nerves, which synapse with nuclei involved in processing perception of pain and pleasure, as well as in addiction. The objective of this prospective study was to investigate the effects of NSS-2 BRIDGE™ on outpatients experiencing acute opioid withdrawal symptoms. We hypothesized that participants using the active NSS-2-BRIDGE™ device would have a reduction in Clinical Opioid Withdrawal Scale (COWS) scores compared to those using the sham device, when monitored at 30-minute intervals. MethodsAdult patients (≥18 years old) who voluntarily presented to the Zephyr outpatient clinic (Santa Anna, CA) were enrolled in the study and fitted with the NSS-2 BRIDGE™ device. Initial COWS scores were recorded at baseline and at 30 minutes intervals, up to 120 minutes. ResultsThe study included 16 participants, 8 subjects in each group. The mean COWS score of the active group decreased from 17.125 at baseline to 5.75 at 30 minutes, a mean decrease of 11.375 (P<0.001). The mean COWS score of the sham group decreased from 16.25 at baseline to 12.875 at 30 minutes, a mean decrease of 3.375 (P=0.186). ConclusionThe active device group showed a statistically and clinically significant mean drop in COWS score compared to the sham group. This study demonstrated that NSS-2 BRIDGE™ can assist in opioid withdrawal and may increase initial treatment retention.

Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice

The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAcBLA) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAcPVT) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAcBLA neurons impairs reward seeking behavior, while silencing of NAcPVT or NAcPVT→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.

Pharmacological characterization of kratom alkaloids at opiate receptors: binding affinities, in vitro and in vivo functional assessments

Kratom (Mitragyna speciosa) is consumed by 10‐15 million individuals in the US for its mood‐elevating effects, as an alternative to traditional opiates for pain relief and to attenuate opiate withdrawal symptoms. Complex natural products, such as kratom, contain a variety of chemicals whose combined effects can only be understood by the meticulous identification and characterization of the individual chemicals and their effects in preclinical model systems. Twenty‐five indole and oxindole kratom alkaloids were evaluated for mu (MOR), delta (DOR) and kappa (KOR) opiate receptors binding affinities, opiate receptor mediated G‐protein activation, inhibition of forskolin stimulated cAMP accumulation and b‐arrestin2 recruitment. Several indole and oxindole alkaloids exhibited partial agonism at the MOR (7‐hydroxymitragynine, corynoxine A &gt; epiallo‐isopaynantheine, isospeciofoline, speciociliatine, corynoxine B &gt; mitragynine, 3‐epicorynoxine B &gt; paynantheine and speciogynine) – all of which also exhibited strong G protein bias. Mitraciliatine and isopaynantheine were weak MOR antagonists. Speciophylline exhibited positive allosteric modulatory activity at the MOR as evidenced by increased affinity of DAMGO binding and potentiation of [met]‐enkephalin‐induced inhibition of forskolin stimulated cAMP activity in the absence of intrinsic activity. Corynoxine A induced displayed similar affinity at the mu opiate receptor as 7 hydroxymitragynine but was less potent in the nociceptive hot plate assay and the mechanical allodynia von Frey test. Corynoxine did not significantly alter respiration or heart rate or induce a conditioned place preference. Results demonstrate the pharmacological complexity of kratom alkaloids and have important implications for determining the combined effects of less abundant indole and oxindole alkaloids with regard to the therapeutic as well as potential harmful effects of kratom.

Ascorbic Acid Effect on Morphine Withdrawal Symptoms in Rats

Introduction: Today, drug addiction is an important healthcare issue. Any helps to drug withdrawal may decrease its prevalence in the society. Ascorbic acid is a component, which can affect neurotransmitter systems as a regulator along with its cofactor role. Noradrenergic and dopaminergic systems are two important neurotransmitter systems in the opiate withdrawal syndrome. It seems that ascorbic acid can decrease the symptoms of opiate withdrawal through regulating the related systems. In this regard, the current study aimed to evaluate the effect of ascorbic acid on the symptoms of morphine withdrawal in Syrian mice. Materials and Methods: Male Syrian mice in eight experimental groups received incremental doses of morphine as 10, 20, 30 and 40 mg/kg within the first, second, third, and fourth days of the experiment, respectively, through intraperitoneal injection, twice a day, and the control group received and equal amount of saline. On the fifth day, six groups of morphine addicts received ascorbic acid with six doses of 10, 50, 100, 200,400 and 800 mg/kg through intraperitoneal injection. Then, naloxone 2 mg/kg was injected to all groups including morphine alone and morphine with acute does of ascorbic acid. Then, withdrawal symptoms were evaluated for 30 minutes. Results: Administration of an acute dose of ascorbic acid reduced dose dependent withdrawal symptoms in such a way that 10, 50, and 100 mg/kg doses of ascorbic acid reduced “writhing” symptom, 200 mg/kg reduced “jumping” symptom, and 400 and 800 mg/kg reduced “climbing, jumping, and standing” symptoms. Conclusion: It seems that ascorbic acid administration can improve the symptoms of opiate withdrawal syndrome. More studies on human population can also indicate the therapeutic effect of ascorbic acid on drug withdrawal.

Percutaneous electrical nerve field stimulation to reduce clincial opiate withdrawal: a case series

ABSTRACT Background Medication-assisted treatment can reduce mortality and withdrawal symptoms, yet treatments can have side effects and are cost ineffective. Research has supported alternative approaches to withdrawal symptoms, specifically percutaneous nerve field stimulator (PNFS); yet, to date, there is a lack of understanding of the initial acceptability within treatment programs. Methods A retrospective case series evaluated PNFS to reduce opioid withdrawal symptoms for five adult patients participating in an in-home withdrawal management program. The device was worn for five consecutive days, in which a licensed practical nurses monitored their care. Evaluation included the clinical opiate withdrawal scale (COWS) and clinical reviews based on self-report and clinician interview. Results Significant reductions were noted for all five participants, with the average COWS score for Day 1 at 19.1 reducing to 2.6 at Day 5. In addition, 2-day post-COWS scores demonstrated a continual reduction to 1.4. Qualitative feedback from the patients was recorded, and generalized themes were recorded and addressed. Conclusions Future controlled, prospective studies should investigate the possibility that PNFS can significantly reduce negative symptoms of opiate withdrawal symptoms, along with providing alternatives to medication-assisted treatments for those who are suffering from opiate use disorder.

Use of clonidine in the management of opiate withdrawal in community patients

AimsClonidine has been used to alleviate symptoms of opiate withdrawal. No validated prescribing schedules exist for the use of Clonidine in opiate detoxification in community patients. We have devised a Clonidine prescribing schedule for adult outpatients seeking opiate detoxification.BackgroundOpiate cessation following prolonged use produces a central noradrenergic (NA) response in the locus coeruleus (LC), causing symptoms that can result in reinstatement of use. Pharmacotherapies for withdrawal are thought to work through decreased NA release in the LC by agonising pre-synaptic alpha-2 adrenoceptors. Clonidine has been used since the 1970s. However, it is off-license in the UK, and superseded by Lofexidine. Though both cause hypotension, this is less marked with Lofexidine, which may be anxiolytic and considered better tolerated. Lofexidine is no longer available in the UK. Specialists may need to resort to Clonidine for those seeking opiate detoxification.MethodWe performed a feasibility study with the primary outcome being tolerability of an outpatient clonidine schedule. Patients (n = 7) were aged between 18 and 65 years (mean 32). Six were prescribed buprenorphine as opiate substitution (OST), and one methadone.Exclusion criteria were in keeping with BNF contraindications.An ECG was obtained for each patient before treatment. A urine drug screen and Clinical Opiate Withdrawal Scale were taken to confirm opiate dependence and withdrawal. Patients self-monitored withdrawal using the Subjective Opiate Withdrawal Scale and daily blood pressure measurements. Standard adjuvants for withdrawal were prescribed.A test dose of 100mcg Clonidine was given to assess for hypotension. If tolerant they received 100mcg QDS, reducing over eight days.Patients were contacted by their recovery worker twice during the period.ResultFive of the seven completed the course, two dropped out due to hypotension. No other adverse effects warranting discontinuation were encountered. Patients reported fatigue and light-headedness as their most troublesome side-effects. Of 3 patients who returned SOWS scores, 2 reported decline by 21/64 and 14/64 respectively. One reported an increase of 49/64 over 8 days. 3 of the 5 subjects who completed the course were not abstinent at completion, citing opiate withdrawal symptoms as causative.ConclusionThere is scope for the safe use of clonidine in the community for motivated individuals. Adequate monitoring of heart rate and blood pressure is required. Starting doses at 100mcg QDS appear well tolerated. Prescribers may wish to reduce this over a longer period to encourage completion and improve tolerability. Further research is needed.

Loperamide toxicity: a case report of turning bowels and twisting points

Introduction: Loperamide is a synthetic mu-receptor agonist used for the treatment of diarrhea however it has recently been illicitly used for a euphoric high or to diminish opiate withdrawal symptoms. In case reports, loperamide abuse has been associated with varied cardiac arrhythmias, most notably ventricular tachycardia and torsades de pointes, presumably related to prolongation of the QTc. Clinical Findings: A 32-year-old male with known prior opioid use disorder presented unresponsive, found to have polymorphic ventricular tachycardia, torsades de pointes, prolonged QTc and QRS, and transient left ventricular (LV) dysfunction. Diagnosis, interventions, and outcomes: When his mental status cleared, the patient reported taking up to 40 pills of loperamide daily with the intent of alleviating opiate withdrawal symptoms. This was felt to be the cause of his QTc prolongation, leading to cardiac toxicity and subsequent dysrhythmia. Patient initially required temporary pacing wire, which was removed hospital day three. He was discharged with suboxone and duloxetine and connected with substance use disorder specialists. Conclusions: We describe a patient with cardiac toxicity associated with loperamide misuse. In the wake of the current opioid epidemic, it is possible that occurrences of loperamide toxicity will increase. It is important for physicians to understand and identify the life-threatening effects of loperamide toxicity in order for proper diagnosis and management.

The Effects of Vitamin D Supplementation on Withdrawal Symptoms and the Expression of Inflammatory Cytokines and Insulin in Patients Under Methadone Maintenance Treatment: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Hypovitaminosis D may be related to some metabolic vulnerable, including metabolic disorders associated with inflammatory cytokines and insulin resistance in subjects undergoing methadone maintenance treatment (MMT). Objectives: This study aimed to determine the impact of vitamin D intake on withdrawal symptoms and genetic response related to inflammatory cytokines and insulin in patients treated with MMT. Methods: This investigation was performed on 40 subjects under MMT to consume either 50,000 IU vitamin D supplements (n = 20) or placebo (n = 20) every 2 weeks for 12 weeks, between April and June 2017 in Kashan, Iran. The clinical opiate withdrawal symptoms (COWS) were evaluated to examine withdrawal scale and gene expression at baseline and after the a 3-month intervention. Statistical analysis of the data was performed using SPSS 18 with Fisher's exact test, t-test, chi-square, and ANCOVA. Also, P values < 0.05 were considered statistically significant. Results: The results of our study showed that compared with the placebo, taking vitamin D downregulated interleukin-1 (IL-1) expression (P = 0.01) in peripheral blood mononuclear cells (PBMCs) of patients under MMT. In addition, consuming vitamin D increased peroxisome proliferator-activated receptor gamma (PPAR-I³) expression (P = 0.01). Administration of vitamin D did not change COWS and IL-8 and tumor necrosis factor-alpha (TNF-I±) expression. Conclusions: According to the results of the present study, vitamin D can be recommended as an adjunct to MMT which may elevate the quality of life and decrease methadone side effects. Copyright © 2020, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Rate and Predictors of Severe Withdrawal Symptoms in an Accelerated Opioid Detoxification Program

Background: Opioid addicts usually quit treatment due to the severe withdrawal symptoms associated with it. Accelerated opioid detoxification programs were launched with the aim of making the detoxification process easier to complete for opioid patients and to improve compliance to the treatment. However, there is limited information on the prevalence of severe withdrawal symptoms and on the risk factors which may lead to such symptoms in accelerated opioid detoxification. The objective of this study, therefore, is to determine the frequency of severe withdrawal symptoms in accelerated detoxification programs and the factors responsible for this. Methods: A total of 191 participants were included in the study. All the participants had been diagnosed with opioid addiction and admitted to Moodist Hospital, where they underwent the Accelerated Detoxification Program (ADP) between November 2018 – July 2019. A naltrexone implant was applied to the participants subsequent to the treatment. The Addiction Profile Index Clinic Form (API-CF) and the Clinical Opiate Withdrawal Symptoms Scale (COWS) were administered to participants during the study process. Results: The Naltrexone implant was applied to all participants at the end of the detoxification treatment. It was found that 9.4% of the people in the ADP treatment process had severe withdrawal symptoms. Furthermore, the presence of severe withdrawal symptoms on the first day was seen to be a factor determining the severity of withdrawal symptoms in the following days. The mean COWS scores and standard deviation of the participants who experienced severe withdrawal symptoms subsequent to the first, second, third, fourth and fifth days of the treatment were 6.64±2.53, 5.47±2.99, 8.14±5.51, 6.13±3.52 and 6.27±2.08, respectively. Another factor that was shown to affect severe withdrawal symptoms was previous outpatient treatments, that is, 80% of the participants who had undergone outpatient treatment before experienced severe withdrawal symptoms, whereas 46% of the participants who had never undergone outpatient treatment before had severe withdrawal symptoms. The mean anxiety score was found to be another factor having an influence on severe withdrawal symptoms. Participants who experienced severe withdrawal symptoms had higher mean anxiety scores; the average anxiety score of those without severe withdrawal symptoms was 0.68, while for those participants with severe withdrawal symptoms, it was 1.07. Conclusions: The rate of completion of the accelerated detoxification program was very high in the study. The higher completion rate takes on particular importance considering the fact that the treatment program was only 5 days. The low rate of confusion, which is one of the major complications associated with accelerated programs, is significant insofar as it demonstrates the aptness of such programs.

Toxicity of agents used for opioid withdrawal: a case-based approach.

Toxicity of agents used for opioid withdrawal: a case-based approach.

Could genetic variations explain variability in neonatal opiate withdrawal syndrome?

Over the past decade, increased use and misuse of opioids during pregnancy have resulted in more than a 5-fold increase in neonatal opioid withdrawal syndrome (NOWS). In 2014, more than 8 out of every 1000 births were affected by maternal opioid abuse, which has created an urgent need for methods to accurately detect, monitor, and treat symptoms of neonatal opiate withdrawal. Current methods of NOWS assessment are based on behavioral findings of irritability, tachypnea, crying, and hyperphagia, and are inherently subjective. In addition, it remains unclear why some infants appear to be severely affected by NOWS and difficult to adequately treat. In this volume of The Journal, Yen et al evaluated salivary gene expression profiles in 100 infants; 50 with neonatal opiate withdrawal and a positive maternal toxicology screen and 50 without antenatal opiate exposure. Male infants with NOWS were more likely to require pharmacotherapy, and these male infants had elevated expression of dopamine receptor type 2 (DRD2), a hypothalamic and reward gene that governs feeding behavior in infants. Moreover, although prenatal opioid exposure upregulated DRD2 in males, it downregulated expression in females. This intriguing finding could explain why a higher proportion of males vs females with NOWS have high feeding intakes that drive the need for pharmacotherapy and suggests symptoms of NOWS may be different in male vs female infants. Opioid-mediated changes in DRD2 expression could help explain why men are more prone than women to substance use disorders as adults. Although this study included a small population, it suggests the possibility that treatment for NOWS may eventually be informed by noninvasive genetic testing and personalized care. Article page 60▸ Sex-Dependent Gene Expression in Infants with Neonatal Opioid Withdrawal SyndromeThe Journal of PediatricsVol. 214PreviewTo evaluate salivary biomarkers that elucidate the molecular mechanisms by which in utero opioid exposure exerts sex-specific effects on select hypothalamic and reward genes driving hyperphagia, a hallmark symptom of infants suffering from neonatal opioid withdrawal syndrome (NOWS). Full-Text PDF

Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients

ABSTRACTBackground: The combination of rilpivirine with methadone may result in complex interactions secondary to the induction of oxidative metabolism by rilpivirine.Research design and methods: TMC278IFD4007 was a single-center, prospective, open-label, multiple-dose study with 12 HIV-infected Chinese participants. The objective was to evaluate the potential effect of rilpivirine on the pharmacokinetics of methadone. The participants received a daily dose of 25 mg rilpivirine for 11 days with individualized methadone ranging from 25 to 100 mg. Pharmacokinetic studies of methadone were conducted on day 1 and 11. Opiate withdrawal symptoms were evaluated.Results: A large inter-subject variability was noted in methadone pharmacokinetics. Rilpivirine increased methadone minimum and maximum plasma concentrations (Cmin; Cmax) and area under the plasma concentration-time curve versus methadone alone (least-square mean ratio; 90% confidence interval) by 5% (1.05; 0.46, 2.39), 5% (1.05; 0.73, 1.52), and 6% (0.75; 0.74, 1.50) as measured in S-methadone, and 5% (1.05; 0.50, 2.22), 5% (1.05; 0.74, 1.50), and 5% (1.05; 0.76, 1.46) as measured in R-methadone, respectively. No opioid withdrawal symptoms or methadone dose adjustments were reported. Co-administration was well tolerated without serious adverse effects or discontinuations.Conclusion: Concomitant administration of rilpivirine was unlikely to have significant effects on the pharmacokinetics of methadone.Trial registration: Chinese Clinical Trial Registry identifier: ChiCTR-TRC-14004908.

Buprenorphine/samidorphan combination for the adjunctive treatment of major depressive disorder: results of a phase III clinical trial (FORWARD-3).

BackgroundThe endogenous opioid system is a fundamental regulator of mood in humans. Previously reported clinical trials have demonstrated the efficacy of the investigational agent buprenorphine/samidorphan (BUP/SAM) combination, an opioid-system modulator, for the adjunctive treatment of major depressive disorder. We present here a third phase III study of different design.MethodsAdult patients with major depressive disorder and inadequate response to antidepressant therapy were enrolled in this double-blind, placebo-controlled, placebo run-in study to evaluate the efficacy, safety, and tolerability of adjunctive BUP/SAM 2 mg/2 mg. Patients with baseline Hamilton Depression Rating Scale score $20 received double-blind placebo in addition to background antidepressant therapy for 4 weeks. Nonresponders were randomized to receive adjunctive BUP/SAM 2 mg/2 mg or placebo for 6 weeks. The primary end point was change in Montgomery–Åsberg Depression Rating Scale (MADRS)-10 total score from randomization at baseline to the end of the 6-week treatment period.ResultsLeast-squares mean change in MADRS-10 score at end of treatment was -4.8 (SE 0.67) in the BUP/SAM 2 mg/2 mg group and -4.6 (SE 0.66) in the placebo group (mean difference -0.3 [SE 0.95], P=0.782). There were no differences in MADRS-based response or remission rates. Overall, 42.9% of the BUP/SAM 2 mg/2 mg group and 34.5% of the placebo group experienced at least one treatment-emergent adverse event during the 6-week treatment period, most of which were mild or moderate in severity. There were no clinically important changes in laboratory parameters, weight, or vital signs and no evidence of abuse potential during treatment or opiate-withdrawal symptoms post treatment.ConclusionEfficacy results in FORWARD-3 measured by change in MADRS-10 score did not meet the primary end point, but postbaseline improvement in MADRS-10 in the BUP/SAM 2 mg/2 mg group was consistent with that seen in previously reported trials. BUP/SAM 2 mg/2 mg was well tolerated.

Comparison of Buprenorphine and Buprenorphine/naloxone in Detoxification of Opioid-dependent Men.

BackgroundBuprenorphine sublingual tablets are now available in Iran for opioid detoxification in clinics. Aim of the present study was to compare the efficiency of buprenorphine with buprenorphine/naloxone in short-term detoxification in a group of Iranian male opioid-dependent patients.MethodsA double-blind trial was carried out on a group of male opioid dependent patients in a psychiatric hospital in Kerman, Iran, during year 2017. A group of 100 men who met the diagnostic criteria for opiate dependence were included in the study from individuals who had referred for detoxification. They were allocated to the two groups receiving either buprenorphine (n = 51) or buprenorphine/naloxone (n = 49). Severity of withdrawal symptoms and signs were evaluated by Clinical Opiate Withdrawal Scale (COWS) and Adjective Rating Scale for Withdrawal (ARSW).FindingsThe mean scores of COWS and ARSW in the two groups treated with buprenorphine and buprenorphine/naloxone significantly reduced from the first day to the fifth day of detoxification (P < 0.050). Moreover, there was no significant difference between the two groups in terms of objective and subjective symptom reduction (P > 0.050).ConclusionBuprenorphine/naloxone is as effective as buprenorphine in controlling opiate withdrawal symptoms.

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.

Kratom, an Emerging Drug of Abuse: A Case Report of Overdose and Management of Withdrawal.

Kratom is an herb indigenous to Southeast Asia with psychoactive opioid compounds, often used as a treatment for chronic pain or opiate withdrawal symptoms. It is legally and readily available via Internet sales and has been identified as an emerging drug of abuse in the United States. Kratom use has been associated with psychosis, seizures, and even death. At lower doses, kratom acts as a stimulant, while at higher doses, it produces analgesia and euphoria. Here, we describe the successful management of kratom overdose and withdrawal in a young man with negative toxicology screens.

Considering Ketamine for Treatment of Comorbid Pain, Depression, and Substance Use Disorders

The use of ketamine for treatment of comorbid pain, depression, and substance use disorders (SUDs) is becoming an option of increasing interest, as multiple clinical studies demonstrate its efficacy. Ketamine's efficacy in this diagnostically complex population is mechanistically based on a wide array of affected brain areas in addition to presynaptic neurons of the spine. Efficacy has been shown in both depressive and pain disorders with durability lasting 3 to 4 weeks after discontinuation of ketamine. Although ketamine itself is a drug of potential abuse when used recreationally, its lasting effects without repeated daily use have also shown promise for patients with SUDs. Assisted psychotherapy concurrent with ketamine treatment can help dependent patients cultivate new perceptions and ideals consistent with sobriety. Decreased opiate cravings in patients with SUDs may be related to ketamine's effects on reducing opiate-induced hyperalgesia. Given this and additional properties, ketamine can help reduce opiate medication burden, augment opiates in the hospice setting, or acutely alleviate symptoms of opiate withdrawal. [ Psychiatr Ann. 2018;48(4):180–183.]

Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine using In Vitro High Throughput Assays.

Mitragynine, a major active alkaloid of Mitragyna speciosa, acts as an agonist on µ-opioid receptors, producing effects similar to morphine and other opioids. It has been traditionally utilized to alleviate opiate withdrawal symptoms. Besides consideration about potency and selectivity, a good drug must possess a suitable pharmacokinetic profile, with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) profile, in order to have a high chance of success in clinical trials. The purity of mitragynine in a Mitragyna speciosa alkaloid extract (MSAE) was determined using Ultra-Fast Liquid Chromatography (UFLC). In vitro high throughput ADMETox studies such as aqueous solubility, plasma protein binding, metabolic stability, permeability and cytotoxicity tests were carried out to analyze the physicochemical properties of MSAE and mitragynine. The UFLC quantification revealed that the purity of mitragynine in the MSAE was 40.9%. MSAE and mitragynine are highly soluble in aqueous solution at pH 4.0 but less soluble at pH 7.4. A parallel artificial membrane permeability assay demonstrated that it is extensively absorbed through the semi-permeable membrane at pH 7.4 but very poorly at pH 4.0. Both are relatively highly bound to plasma proteins (> 85 % bound) and are metabolically stable to liver microsomes (> 84 % remained unchanged). In comparison to MSAE, mitragynine showed higher cytotoxicity against WRL 68, HepG2 and Clone 9 hepatocytes after 72 h treatment. The obtained ADME and cytotoxicity data demonstrated that both MSAE and mitragynine have poor bioavailability and have the potential to be significantly cytotoxic.