Establishing a research agenda for the study and assessment of opioid withdrawal.

The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period. We posit that underinvestment has occurred in part due to an underdeveloped understanding of opioid withdrawal syndrome. This Personal View summarises substantial gaps in our understanding of opioid withdrawal that are likely to continue to limit major advancements in its treatment. There is no firm consensus in the field as to how withdrawal should be precisely defined; 10-550 symptoms of withdrawal can be measured on 18 scales. The imprecise understanding of withdrawal is likely to result in overestimating or underestimating the severity of an individual's withdrawal syndrome or potential therapeutic effects of different candidate medications. The severity of the opioid crisis is not remitting, and an international research agenda for the study and assessment of opioid withdrawal is necessary to support transformational changes in withdrawal management and treatment of opioid use disorder. Nine actionable targets are delineated here: develop a consensus definition of opioid withdrawal; understand withdrawal symptomatology after exposure to different opioids (particularly fentanyl); understand precipitated opioid withdrawal; understand how co-exposure of other drugs (eg, xylazine and stimulants) influences withdrawal expression; examine individual variation in withdrawal phenotypes; precisely characterise the protracted withdrawal syndrome; identify biomarkers of opioid withdrawal severity; identify predictors of opioid withdrawal severity; and understand which symptoms are most closely associated with treatment attrition or relapse. The US Food and Drug Administration recently established a formal indication for opioid withdrawal that has invigorated interest in drug development for opioid withdrawal management. Action is now needed to support these interests and help industry identify new classes of medications so that real change can be achieved for people with opioid use disorder.

[Assessment of alcohol withdrawal syndrome: new perspectives]. / Az alkoholmegvonásos szindróma ellátása: új perspektívák.

Alcohol withdrawal syndrome is one of the most important consequences of alcohol use disorder, a complex neuropsychiatric disorder, which is firstly treated in non-specific and secondly in psychiatric/addictive in- or outpatient units. On the other hand, alcohol withdrawal syndrome is one of the most important outcomes of the severity of alcohol use disorder, further, it can lead to the development of alcohol-related seizure and delirium tremens. Hence, early recognition and optimal treatment of alcohol withdrawal syndrome have a critical importance. Therefore, the main goal of the present review was - by systematically summarizing the scientific data published during the past two decades - to form a unique diagnostic and therapeutic algorithm. During the recognition and the course of alcohol withdrawal syndrome, the Clinical Institute Withdrawal Assessment for Alcohol, Revised scale, while in the risk assessment the Prediction of Alcohol Withdrawal Severity Scale are the recommended psychometric tools. Benzodiazepines are the key elements of the pharmacotherapy of alcohol withdrawal syndrome. Many studies have evaluated that diazepam, chlordiazepoxide, lorazepam and oxazepam with distinct indications have sufficient evidence in the treatment of alcohol withdrawal syndrome. However, in the past few years some authors have recommended the importance of non-benzodiazepine medications. The efficacy of propofol, phenobarbital, carbamazepin, oxcarbamazepin and alpha-2 receptor agonists in the treatment of alcohol withdrawal syndrome have been revealed. Furthermore, it has been evaluated that benzodiazepines are recommended in the treatment of alcohol-related seizure and delirium tremens. In the present review, our aim was to construct a unique, up-to-date diagnostic and therapeutic algorithm by summarizing the related papers published during the past two decades. Hence this scheme may be useful in the optimal treatment of patients diagnosed with alcohol use disorder and it could help to conduct further clinical researches. Orv Hetil. 2023; 164(38): 1487-1496.

Assessment of a modified MINDS-based protocol for management of alcohol withdrawal syndrome on an inpatient medical service.

OBJECTIVE: To determine if a novel symptom-based alcohol withdrawal syndrome (AWS) protocol in a US Veterans cohort leads to significant clinical improvements in patient outcomes and safety. BACKGROUND: Prior studies of AWS management, oftentimes using the revised version of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) index, have demonstrated the effectiveness of symptom-triggered therapy for AWS. The Minnesota Detoxification Scale (MINDS) is an alternative to the CIWA-Ar index but remains unevaluated outside of the intensive care unit (ICU) setting. This study assesses outcomes in AWS management prior to and after the implementation of a novel MINDS-based AWS protocol (SDAWP) utilizing a revised MINDS index (MINDS-rev) in an inpatient medical ward setting. METHODS: Retrospective cohort study including encounters prior to (n = 342) and after (n = 338) the implementation of the protocol. Pre- and post-protocol encounters were selected by combinations of diagnostic codes and charting elements. Outcome measures of AWS management were obtained in both groups. The primary endpoint was median total benzodiazepine exposure. Secondary outcomes included median length of hospitalization, median duration of benzodiazepine administration, and the incidence of complications. RESULTS: The median total benzodiazepine exposure in the post-SDAWP group was significantly lower than the pre-SDAWP group (21.2 vs. 12.0 mg, p < 0.0001) and for a significantly shorter median duration of time (4.0 vs. 3.0 days, p < 0.0001). There was no significant difference in the median length of stay (4.0 vs. 4.0 days, p = 0.50). The incidence of delirium tremens (21 vs. 7, p = 0.01) and need for transfer to a higher level of care (33 vs. 12, p = 0.002) was significantly lower in the post-SDAWP group. CONCLUSION: The SDAWP has provided significant improvements in AWS management in our institution and may potentially serve as a template for wider use in other inpatient settings.

Working Toward a Gold Standard: The Severity of Ethanol Withdrawal Scale (SEWS) Versus the Clinical Institute Withdrawal Assessment Alcohol Scale (CIWA-Ar).

AIM: Proving the Severity of Ethanol Withdrawal Scale (SEWS) significantly reduces Alcohol Withdrawal Syndrome (AWS) treatment Time on Medication Protocol (TOMP). METHOD: Head-to-head Quality Assurance outcome compared separate cohorts of SEWS or Clinical Institute Withdrawal Assessment Alcohol Scale, Revised (CIWA-Ar) data using Student's t and Wilcoxon tests. RESULTS: SEWS-driven treatment (n = 244) reduced TOMP to 2.2 days versus 3.4 days for CIWA-Ar (n = 137); P < 0.0001. CONCLUSION: The SEWS is the superior measure of AWS symptoms.

Assessment of abuse potential of carfentanil.

Carfentanil, as a fentanyl analogue, is a potent synthetic opioid. It has been controlled in many countries, and its emergence has been highlighted by many recent reports. However, although discriminative stimulus effects of carfentanil in rats had been reported, its abuse potential has not been fully evaluated. In this study, we evaluated the abuse potential of carfentanil via the tests of conditioned place preference (CPP), drug self-administration and naloxone-precipitated opioid withdrawal assay, compared with fentanyl and heroin. Carfentanil exhibited significant place preference at a minimum dose of 1 µg/kg in mice, whereas fentanyl and heroin induced significant place preference at the minimum doses of 100 µg/kg and 1000 µg/kg, respectively. In the drug-substitution test in heroin self-administered rats (50 µg/kg/infusion), carfentanil and fentanyl acquired significant self-administrations above saline levels from 0.05-0.1 and 0.1-10.0 µg/kg/infusion, respectively. Carfentanil induced the maximum number of infusions at 0.1 µg/kg, whereas fentanyl and heroin at 1 and 25 µg/kg, respectively. In short, carfentanil showed the highest potency to induce CPP and self-administration. Furthermore, repeated treatment with escalating doses of carfentanil, fentanyl or heroin induced typical withdrawal symptoms in mice, including a greater number of jumping and weight loss than saline group. This indicated that carfentanil could produce physical dependence similar to fentanyl and heroin. Taken together, the present study demonstrated the higher abuse potential of carfentanil compared with fentanyl and heroin. The rank order of abuse potential for these compounds is carfentanil > fentanyl > heroin.

Correlation Between and Nursing Satisfaction With CIWA-Ar, mMINDS, and SEWS Scoring Tools for the Assessment of Severe Alcohol Withdrawal Syndrome in ICU Patients.

BACKGROUND: Management of alcohol withdrawal syndrome (AWS) requires bedside assessments of symptom severity to guide therapies. Commonly used assessment tools are the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the modified Minnesota Detoxification Scale (mMINDS) and the Severity of Ethanol Withdrawal Scale (SEWS). OBJECTIVE: To determine strength of correlation between the CIWA-Ar, mMINDS, and SEWS for bedside assessment of severe AWS and to survey nurses regarding ease of use of each tool. METHODS: A single-center prospective correlation study of the three assessment tools performed by bedside nurses on patients with AWS followed by a questionnaire assessing ease of use of each tool (1 being the easiest and 9 being the hardest). RESULTS: A total of 66 correlation assessments were performed by 49 nurses in 21 patients with AWS. Bedside CIWA-Ar, mMINDS, and SEWS were 14 ± 8.3, 13.9 ± 6.5, and 10.1 ± 4.5, respectively. The Pearson correlation coefficients were 0.814 (95% CI, 0.714-0.881) between CIWA-Ar and mMINDS; 0.722 (95% CI, 0.585-0.820) between CIWA-Ar and SEWS; and 0.658 (95% CI, 0.498-0.775) between SEWS and mMINDS. Nurse ratings for ease of use were 4 ± 2.3 for CIWA-Ar, 2.9 ± 2 for mMINDS (p=0.0044 vs. CIWA-Ar), and 4.8 ± 2.1 for SEWS (p=0.036 vs. CIWA-Ar, p<0.0001 vs. mMINDS). Forty-six (69.7%) respondents preferred mMINDS versus 14 (21.2%) and 6 (9.1%) respondents favored CIWA-Ar and SEWS, respectively. CONCLUSION: Correlations between the three scoring tools in severe AWS are robust. Only mMINDS was considered easy to use by nurses. It was the preferred tool.

Assessment of Kratom Use Disorder and Withdrawal Among an Online Convenience Sample of US Adults.

INTRODUCTION: Since 2007, kratom use in the United States has increased, centered around nonmedical self-treatment of pain, psychiatric, and substance use disorder symptoms. Reports of kratom withdrawal have emerged amidst description of therapeutic effects, yet we know little about disordered use. Our objective was to assess Diagnostic and Statistical Manual-5 substance use disorder for kratom ("kratom use disorder," KUD) and examine kratom withdrawal symptoms among those who ever used regularly. We also sought to identify clinical characteristics of respondents who qualified for current, remitted, or never KUD. METHODS: Between April and May 2021, we re-recruited online respondents who reported lifetime kratom use on an unrelated survey into our cross-sectional kratom survey study, permitting a diverse sample of current and former kratom-using persons. RESULTS: A total of 129/289 (44.6%) evaluable surveys were obtained. Over half (52.7%) of respondents never met KUD diagnostic criteria; 17.8% were assessed remitted, and 29.5% met current (past-year) KUD threshold. For past-year KUD, severity was: 14.0% mild, 7.0% moderate, and 8.5% severe. Pain, psychiatric symptoms, and polydrug use were found across all groups. KUD symptoms reflected increased use, tolerance, withdrawal, unsuccessful quit attempts, and craving; 9.3% reported decreases in important social, occupational, or recreational activities because of use. Withdrawal symptoms were moderate and included gastrointestinal upset, restlessness, anxiety, irritability, fatigue/low energy, and craving. CONCLUSIONS: As assessed here, tolerance and withdrawal are primary KUD features rather than psychosocial impairments. As kratomis often used among persons with a myriad of health conditions, clinicians should be aware of and assess for kratom use and withdrawal.

Outcomes of Minnesota Detoxification Scale (MINDS) Assessment With High-Dose Front Loading Diazepam Treatment for Alcohol Withdrawal in Hospitalized Patients.

BACKGROUND: Benzodiazepines are the gold standard for alcohol withdrawal treatment but choice and dosing vary widely. In 2015, our institution implemented a Minnesota detoxification scale (MINDS) and single standardized high-dose diazepam based protocol for treatment of alcohol withdrawal to replace multiple Clinical Institute Withdrawal Assessment for Alcohol (CIWA) based protocols using lower dose benzodiazepines. We compared use of MINDS versus CIWA assessment protocols with high front loading diazepam treatment in care of patient experiencing alcohol withdrawal during hospitalization. METHODS: Retrospective cohort study of hospitalized patients experiencing alcohol withdrawal to statistically analyze difference in outcomes between CIWA based lower benzodiazepine dose protocols used in 2013-2015 versus the MINDS based high-dose front-loading diazepam protocol used in 2015-2017. RESULTS: Patients treated with MINDS based high dose diazepam protocol were less likely to have physical restraints used (AOR = 0.8, CI: 0.70-0.92), had a shorter hospital length of stay, and fewer days on benzodiazepines (p < 0.001). Patients were more likely to be readmitted to the hospital within 30 days (AOR = 1.13, CI: 1.03-1.26) in MINDS based diazepam treatment group. Total diazepam equivalent dosing was similar in both groups. Mortality rates and ICU use rates were similar between the groups. CONCLUSIONS: Higher dose front loading long acting benzodiazepine can be safely used with beneficial outcomes in hospitalized alcohol withdrawal patients.

The Spectrum of Alcohol Use: Epidemiology, Diagnosis, and Treatment.

In the United States, alcohol is the most common substance used and the spectrum of unhealthy alcohol use is highly prevalent. Complications of unhealthy alcohol use affect nearly every organ system. One of the most frequent and potentially life-threatening of these complications is alcohol withdrawal syndrome for which benzodiazepines remain first-line therapy. Pharmacologic treatment of alcohol use disorder, the most severe form of unhealthy alcohol use, is underutilized despite the availability of multiple effective medications. Although behavioral therapies are an important component of treatment, they are overemphasized at the expense of pharmacotherapy.

Evaluation of the course and treatment of Alcohol Withdrawal Syndrome with the Clinical Institute Withdrawal Assessment for Alcohol - Revised: A systematic review-based meta-analysis.

BACKGROUND: Although the Clinical Institute Withdrawal Assessment for Alcohol - Revised (CIWA-Ar) is a gold standard tool for the clinical evaluation of alcohol withdrawal syndrome (AWS), a systematic analysis using the total scores of the CIWA-Ar as a means of an objective follow-up of the course and treatment of AWS is missing. The aims of the present study were to systematically evaluate scientific data using the CIWA-Ar, to reveal whether the aggregated CIWA-Ar total scores follow the course of AWS and to compare benzodiazepine (BZD) and non-benzodiazepine (nBZD) therapies in AWS. METHODS: 1054 findings were identified with the keyword "ciwa" from four databases (PubMed, ScienceDirect, Web of Science, Cochrane Registry). Articles using CIWA-Ar in patients treated with AWS were incorporated and two measurement intervals (cumulative mean data of day 1-3 and day 4-9) of the CIWA-Ar total scores were compared. Subgroup analysis based on pharmacotherapy regimen was conducted to compare the effectiveness of BZD and nBZD treatments. RESULTS: The random effects analysis of 423 patients showed decreased CIWA-Ar scores between the two measurement intervals (BZD: d = -1.361; CI: -1.829 < δ < -0.893; nBZD: d = -0.858; CI: -1.073 < δ < -0.643). Sampling variances were calculated for the BZD (v1 = 0.215) and the nBZD (v2 = 0.106) groups, which indicated no significant group difference (z = -1.532). CONCLUSIONS: Our findings support that the CIWA-Ar follows the course of AWS. Furthermore, nBZD therapy has a similar effectiveness compared to BZD treatment based on the CIWA-Ar total scores.

Guidelines for the assessment and management of addiction in the hospitalized patient with opioid use disorder: a twenty-first century update.

While there have been many articles published on managing the medical sequelae of opioid use disorder in specific patient populations or settings, there is a dearth of literature on assessing and managing opioid use disorder in the acute hospital setting. In 1975, Fultz and Senay published proposed guidelines on the management of what they called the "hospitalized narcotic addict" Fultz and Senay (Ann Intern Med 82(6):815-818, 1975). Since then, many new developments in the treatment of opioid use disorder have occurred. In our experience, services in the acute inpatient hospital turn to psychiatric consultation teams for recommendations on how to manage these complicated and, sometimes, difficult patients. This article serves to provide the internal medicine physician a foundation of understanding how to address the main issues in hospitalized patients with opioid use disorder on a general medical or surgical floor.

Iatrogenic Opiate Withdrawal in Pediatric Patients: Implementation of a Standardized Methadone Weaning Protocol and Withdrawal Assessment Tool.

Methadone is frequently used to prevent withdrawal symptoms secondary to intended therapeutic opiate exposure. Absence of a standardized dose weaning strategy potentially results in increased exposure to narcotics and/or withdrawal symptoms. We sought to quantify the effect of implementing a standardized methadone weaning protocol and withdrawal assessment tool on methadone exposure and opiate withdrawal in pediatric patients receiving 5 or more days of continuous morphine or fentanyl infusions. The preintervention phase included patients weaned off of opiate infusions before implementation of a standardized weaning protocol and withdrawal symptom scoring tool. Patients in the postintervention phase were started on a standardized methadone wean based on total duration and dose of continuous opiate infusion exposure in the 24 hours preceding methadone initiation. Patients received either a 5- or 10-day wean, with the total daily methadone dose reduced by 20% daily or every other day, respectively. Patients in the postintervention phase were monitored for withdrawal using the withdrawal assessment tool (WAT-1). Postintervention patients were compared to preintervention patients treated with methadone. Total methadone duration decreased significantly from a median of 17 (13-22 interquartile range [IQR]) to 5 (5-10 IQR) days (P = .00001) after implementation of the methadone weaning protocol. Number of morphine boluses administered increased from a median of 3 (0-6 IQR) to 4 (0-5 IQR) doses per patient (P = .45). Demographic data were similar between both groups. Patients in the postintervention phase had significant reductions in methadone exposure after implementation of a standardized methadone weaning protocol and assessment tool.

Alcohol Withdrawal Syndrome in Neurocritical Care Unit: Assessment and Treatment Challenges.

Alcohol withdrawal syndrome (AWS) can range from mild jittery movements, nausea, sweating to more severe symptoms such as seizure and death. Severe AWS can worsen cognitive function, increase hospital length of stay, and in-hospital mortality and morbidity. Due to a lack of reliable history of present illness in many patients with neurological injury as well as similarities in clinical presentation of AWS and some commonly encountered neurological syndromes, the true incidence of AWS in neurocritical care patients remains unknown. This review discusses challenges in the assessment and treatment of AWS in patients with neurological injury, including the utility of different scoring systems such as the Clinical Institute Withdrawal Assessment and the Minnesota Detoxification Scale as well as the reliability of admission alcohol levels in predicting AWS. Treatment strategies such as symptom-based versus fixed dose benzodiazepine therapy and alternative agents such as baclofen, carbamazepine, dexmedetomidine, gabapentin, phenobarbital, ketamine, propofol, and valproic acid are also discussed. Finally, a treatment algorithm considering the neurocritical care patient is proposed to help guide therapy in this setting.

[Assessment and Treatment of Alcohol Withdrawal Syndrome].

Alcohol withdrawal syndrome (AWS) is the most common and well-known condition occurring after intentional or unintentional cessation or decreasing heavy drinking. Approximately 5-10% of these people are suffering from serious medical and psychiatric problems, withdrawal seizures, perceptual disturbances, and delirium tremens. Despite acute medical conditions with the high mortality of severe AWS, proper management could decrease the severity and mortality of AWS. The Clinical Institute withdrawal assessment for alcohol-revised version is a valid, reliable, and sensitive instrument for assessing the clinical course and the treatment monitoring of alcohol withdrawal. Benzodiazepine is the pharmacotherapy of choice for alcohol withdrawal. Diazepam or lorazepam treatment is best initiated early in the course of alcohol withdrawal to prevent progression to more severe withdrawal. There are three strategies for the pharmacotherapy of AWS. After the treatment of AWS, most patients should be managed or treated by the continuing care, including the psychosocial treatments, community-based management, and programs for preventing recurrence of AWS.

Evaluation of a Novel Protocol for Assessment and Treatment of Alcohol Withdrawal Syndrome in Psychiatric Inpatients.

BACKGROUND AND OBJECTIVES: Despite the high incidence of alcohol withdrawal syndrome (AWS) in psychiatric inpatients, standardized methods for assessing and treating AWS have been studied only once before in this population. We evaluated a novel AWS assessment and treatment protocol designed for psychiatric inpatients. METHODS: This retrospective cohort study evaluated outcomes before and after implementation of the protocol. We collected consecutive data on patients (N = 138) admitted to inpatient psychiatric units at a single center. Participants were patients admitted for nonsubstance-related psychiatric reasons, who were also at risk for developing AWS. Those who developed AWS were treated with either (a) treatment as usual (TAU) or (b) a novel standardized protocol. The primary outcome was duration of benzodiazepine treatment for symptoms of alcohol withdrawal. Secondary outcomes included cumulative benzodiazepine dose administered, treatment duration, and incidence of complications. RESULTS: Of 138 participants, 83 received TAU and 55 were assessed and treated with the novel protocol. Median duration of benzodiazepine treatment following protocol implementation was 19.7 hours (interquartile range [IQR], 0-46) prior to implementation (TAU) and 0 hours (IQR, 0-15) following protocol implementation (protocol group) (P < .0001). Median benzodiazepine dose (in diazepam equivalents) administered to participants was 30 mg (IQR, 0-65) for TAU and 5 mg (IQR, 0-30) for the protocol group (P < .001). Adverse events before and after implementation occurred in 4.8% and 0%, respectively (P = .15). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This study provides preliminary evidence for the efficacy and safety of a novel standardized AWS protocol for psychiatric inpatients. This is the first known study assessing an AWS assessment and treatment protocol designed for psychiatric inpatients. (Am J Addict 2020;29:500-507).

Assessment and treatment of the withdrawal syndrome in paediatric intensive care units: Systematic review.

BACKGROUND: Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and there is currently no gold standard method for diagnosis. In addition, the assessment scales validated in children are scarce. This paper aims to identify and describe both the paediatric diagnostic and assessment tools for the IWS and the treatments for the IWS in critically ill paediatric patients. METHODS: A systematic review was conducted according to the PRISMA guidelines. This review included descriptive and observational studies published since 2000 that analyzed paediatric scales for the evaluation of the iatrogenic withdrawal syndrome and its treatments. The eligibility criteria included neonates, newborns, infants, pre-schoolers, and adolescents, up to age 18, who were admitted to the paediatric intensive care units with continuous infusion of hypnotics and/or opioid analgesics, and who presented signs or symptoms of deprivation related to withdrawal and prolonged infusion of sedoanalgesia. RESULTS: Three assessment scales were identified: Withdrawal Assessment Tool-1, Sophia Observation Withdrawal Symptoms, and Opioid and Benzodiazepine Withdrawal Score. Dexmedetomidine, methadone and clonidine were revealed as options for the treatment and prevention of the iatrogenic withdrawal syndrome. Finally, the use of phenobarbital suppressed symptoms of deprivation that are resistant to other drugs. CONCLUSIONS: The reviewed scales facilitate the assessment of the iatrogenic withdrawal syndrome and have a high diagnostic quality. However, its clinical use is very rare. The treatments identified in this review prevent and effectively treat this syndrome. The use of validated iatrogenic withdrawal syndrome assessment scales in paediatrics clinical practice facilitates assessment, have a high diagnostic quality, and should be encouraged, also ensuring nurses' training in their usage.

Pharmacologic and clinical assessment of kratom: An update.

PURPOSE: This article presents updated information on kratom (Mitragyna speciosa), a natural opioid with stimulant properties that is currently sold in the United States without a prescription. SUMMARY: Kratom exerts opioid and alpha-2 agonistic effects, as well as anti-inflammatory and mild stimulant effects. Respiratory depression has not been commonly reported, but kratom does cause a host of adverse effects. While kratom may have a role in patients who are in chronic pain or dependent on opioid painkillers or heroin, this needs to be established in clinical trials. Kratom may have drug interactions as both a cytochrome P-450 system substrate and inhibitor. Kratom does not appear in normal drug screens and, especially when ingested with other substances of abuse, may not be recognized as an agent of harm. There are numerous cases of death in kratom users, but many involved polypharmaceutical ingestions. There are assessments where people have been unable to stop using kratom therapy and withdrawal signs/symptoms occurred in patients or their newborn babies after kratom cessation. Both banning and failure to ban kratom places people at risk; a middle-ground alternative, placing it behind the pharmacy counter, might be useful. CONCLUSION: Kratom has a unique pharmacologic profile that might offer advantages over other opioids, but its high abuse liability, potential for drug interactions and adverse events, and inadequate research into the balance of benefits to harm are concerning. There is mounting information on the adverse events associated with kratom use and potential treatments that can be useful to clinicians.

Comparative Assessment of the Effectiveness of Noncompetitive NMDA Receptor Antagonists Amantadine and Hemantane in Morphine Withdrawal Syndrome Model.

Activities of noncompetitive NMDA receptor antagonists (aminoadamantane derivatives) were assessed in random-bred rats with modeled morphine withdrawal syndrome. A single intraperitoneal injection of hemantane (10 or 20 mg/kg) significantly and dose-dependently moderated some behavioral symptoms (teeth-chattering, ptosis, and vocalization) and reduced total score of morphine withdrawal syndrome. In morphine-abstinent rats, hemantane partially prevented the decrease in the thresholds of tactile sensitivity, but had no effect on locomotor activity and body weight loss. Under conditions of morphine withdrawal, intraperitoneal injection of amantadine (10 or 20 mg/kg) decreased motor activity and promoted body weight loss in parallel with the development of mechanical allodynia, but had no effect on the total withdrawal score. Comparison of aminoadamantane derivatives by behavioral and physiological parameters demonstrated the advantage of hemantane during morphine abstinence indicating the need of its study as a promising anti-addiction remedy.

Synthetic cannabinoid use disorder: an update for general psychiatrists.

OBJECTIVE: Synthetic cannabinoid use disorder is emerging as a significant clinical issue. This article provides the general psychiatrist with an overview of the physical and psychiatric adverse effects of chronic synthetic cannabinoid use, as well as specific clinical responses. METHOD: We performed electronic searches of Ovid MEDLINE and Ovid Embase to identify key articles, of all methodological designs, published up to June 2018. RESULTS: The available evidence suggests that, compared to cannabis, use of synthetic cannabinoids is associated with the more rapid development of dependence, increased psychiatric risks and complex withdrawal, and serious physical adverse effects that include seizures, cardiotoxicity and death, denoting a potential need for more intensive management. CONCLUSION: When synthetic cannabinoid use is identified, along with management of acute physical and psychiatric adverse effects, psychotherapeutic strategies to reduce use and/or harm are recommended.