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Objective: Antipsychotics remain the first‐line treatment for people diagnosed with psychotic disorders despite adverse effects which lead many people to stop their medication. Many stop without the support of the prescriber, who may fear relapse. The objective of this study is to better understand the process of withdrawal from antipsychotics, from the perspective of people taking antipsychotics. Design: Online survey. Methods: An international online survey elicited quantitative responses about pre‐withdrawal planning (560) and qualitative responses about what was helpful and unhelpful when withdrawing from antipsychotics (443). Responses came from users of antipsychotics in 29 countries. Results: Forty‐seven per cent did not consult their psychiatrist before discontinuing. Only 40% made preparations, most commonly making a plan, gathering information and informing family. The most frequently reported helpful factors were focussing on the benefits of getting off the drugs (including ending adverse effects and feeling more alive), information about withdrawal symptoms and how to withdraw safely, withdrawing slowly, and support from psychologists, counsellors and psychotherapists. The most common unhelpful factor was the psychiatrist/doctor, largely because of their lack of knowledge, refusal to support the patient's wishes and the threat or use of coercion. Conclusions: Evidence‐based, respectful, collaborative responses to patients' concerns about adverse effects and desires to withdraw would probably reduce relapse rates and improve long‐term outcomes. It would definitely help end pervasive breaching of the principle of informed consent and human rights legislation. [ABSTRACT FROM AUTHOR]

The management of sedation in critically ill adults poses a unique challenge to clinicians. Dexmedetomidine, an α2 agonist, has a unique mechanism and favorable pharmacokinetics, making it an attractive intravenous option for sedation and delirium in the intensive care unit. However, patients may be at risk for withdrawal with prolonged use, adding to the complexity of sedation and agitation management in this patient population. Enteral α2 agents have the benefit of cost savings and ease of administration, thus playing a role in the ability to decrease intravenous sedative use and prevent dexmedetomidine withdrawal. Clonidine and guanfacine are the two most common enteral α2 agents utilized for this purpose, however, there is a paucity of evidence regarding the comparative benefit between the two agents. The decision to use one vs the other agent should be determined based on their differing pharmacology, pharmacokinetics, and side effect profile. The most effective dosing strategy for these agents is also unknown. Ultimately, more robust literature is required to determine enteral α2 agonists place in therapy. This narrative review evaluates the currently available literature on the use of α2 agonists in critically ill adults with an emphasis on sedation, delirium, and withdrawal. [ABSTRACT FROM AUTHOR]

Objectives: The link between cannabis use and psychotic symptoms or disorders is well known. However, the relation between cannabis withdrawal and psychotic symptoms is less studied. Methods: To our knowledge, this is the first publication of an observational systematic report of cannabis-induced psychotic disorder with onset during withdrawal. Here, we review patients presenting to a major emergency room in Montreal between January 2020 and September 2023 in a context of psychotic symptoms following cannabis cessation. Results: In total, seven male and one female patients presented at the peak of cannabis withdrawal with acute psychotic symptoms, representing less than 1% of all emergency service admissions. Conclusions: We discuss current knowledge regarding the endocannabinoid system and dopamine homeostasis to formulate hypotheses regarding these observations. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to estimate health state utility values (HSUVs) for the key health states found in opioid use disorder (OUD) cost-effectiveness models in the published literature. Methods: Data obtained from six trials representing 1,777 individuals with OUD. We implemented mapping algorithms to harmonize data from different measures of quality of life (the SF-12 Versions 1 and 2 and the EQ-5D-3 L). We performed a regression analysis to quantify the relationship between HSUVs and the following variables: days of extra-medical opioid use in the past 30 days, injecting behaviors, treatment with medications for OUD, HIV status, and age. A secondary analysis explored the impact of opioid withdrawal symptoms. Results: There were statistically significant reductions in HSUVs associated with extra-medical opioid use (-0.002 (95% CI [-0.003,-0.0001]) to -0.003 (95% CI [-0.005,-0.002]) per additional day of heroin or other opiate use, respectively), drug injecting compared to not injecting (-0.043 (95% CI [-0.079,-0.006])), HIV-positive diagnosis compared to no diagnosis (-0.074 (95% CI [-0.143,-0.005])), and age (-0.001 per year (95% CI [-0.003,-0.0002])). Parameters associated with medications for OUD treatment were not statistically significant after controlling for extra-medical opioid use (0.0131 (95% CI [-0.0479,0.0769])), in line with prior studies. The secondary analysis revealed that withdrawal symptoms are a fundamental driver of HSUVs, with predictions of 0.817 (95% CI [0.768, 0.858]), 0.705 (95% CI [0.607, 0.786]), and 0.367 (95% CI [0.180, 0.575]) for moderate, severe, and worst level of symptoms, respectively. Conclusion: We observed HSUVs for OUD that were higher than those from previous studies that had been conducted without input from people living with the condition. Plain English Summary: Thus far, health-related quality of life estimates for patients with opioid use disorder in the United States are limited, and importantly, they were not generated from studies among people living with the condition. This study extracted data from six clinical trials providing data among 1,777 people with opioid use disorder, made publicly available by the National Institutes of Health, to produce estimates of health-related quality of life. Our study found higher health-related quality of life estimates as compared to previous studies, modest impact of medications for opioid use disorder and strong impact of withdrawal symptoms on this outcome. These higher values among people with opioid use disorder might reflect the very negative perception of this condition among members of the general population (among whom these estimates have been generated previously). However, these relatively high estimates could also reflect an adaptation to the condition or a lack of awareness of associated-health damage in the context of dependence. The low number of observations providing data on medications for opioid use disorder led to high uncertainty around related estimates of health-related quality of life, but our findings could also reflect real experiences by patients in the absence of the positive effects of non-medication opioids, which deserve more attention in clinical practice. Our study suggests that systematically measuring withdrawal symptoms and representing these in health economic models might provide a more accurate representation of health-related quality of life among people with opioid use disorder and therefore of the impact and cost-effectiveness of interventions. Clinical trial registration details: The information reported here results from secondary analyses of data from clinical trials conducted by the National Institute on Drug Abuse (NIDA). Specifically, data from NIDA-CTN-0001 (NCT00032955 and 'Buprenorphine/Naloxone versus Clonidine for Inpatient Opiate Detoxification'), NIDA-CTN-0002 (NCT00032968 and 'Buprenorphine/Naloxone versus Clonidine for Outpatient Opiate Detoxification'), NIDA-CTN-0009 (NCT00067158 and 'Smoking Cessation Treatment with Transdermal Nicotine Replacement Therapy in Substance Abuse Rehabilitation Programs'), NIDA-CTN-0030 (NCT00316277 and 'A Two-Phase Randomized Controlled Clinical Trial of Buprenorphine/Naloxone Treatment Plus Individual Drug Counseling for Opioid Analgesic Dependence'), NIDA-CTN-0049 (NCT01612169 and 'Project HOPE - Hospital Visit as Opportunity for Prevention and Engagement for HIV-Infected Drug Users'), NIDA-CTN-0051 (NCT02032433 and 'Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment') were included. NIDA databases and information are available at (https://datashare.nida.nih.gov). Additional observational data was used to equate different measures of health-related quality of life onto the same scale using psychometric methods. These data included the National Health Measurement Study (which is available at https://www.disc.wisc.edu/) and the Household Component files for the Medical Expenditure Panel Survey (which is available at https://meps.ahrq.gov/mepsweb/). [ABSTRACT FROM AUTHOR]

Background: Untreated pain is a source of significant physical and psychosocial distress in patients with cancer. While guidelines for prescribing opioids have improved the treatment of cancer-related pain, all patients who take opioids are at risk for developing opioid-induced respiratory depression (OIRD). The current treatment for OIRD is naloxone although guidelines are highly variable on initial dose and indication. Patients with cancer on chronic opioids are at risk for increased suffering due to naloxone-induced opioid withdrawal and loss of pain control. Aim: A review of the evidence for the safety and benefits of using buprenorphine instead of naloxone for reversal of OIRD in patients prescribed chronic opioids for cancer-related pain. Methods: A realist review of the literature was completed following the RAMSES Framework. An iterative literature search of electronic databases was used to identify appropriate literature relating to buprenorphine and naloxone safety and use as reversal agents in OIRD. Results: While naloxone does reverse OIRD it does have the risk of pulmonary edema and research has consistently shown that naloxone is usually given for the wrong indications and/or at an inappropriate dose for patients on chronic opioids for cancer-related pain. Buprenorphine has been shown to safely reverse OIRD with less incidence and severity of withdrawal and uncontrolled pain when compared to naloxone. Conclusions: Because of the potential for decreased opioid withdrawal-associated symptoms, this review argues that buprenorphine warrants additional study and consideration to replace naloxone as the first-line rescue medication for patients with cancer on chronic opioids who experience OIRD. [ABSTRACT FROM AUTHOR]

β‐Phenyl‐γ‐aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ‐aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online without a prescription. Increased public awareness of phenibut has led to a growing number of reports of acute intoxication and withdrawal. In this review, we describe the pharmacology of phenibut, the presentation and management of acute intoxication, and regulatory issues, placing particular emphasis on the treatment of acute withdrawal, for which there are no comparative studies. Among 29 cases of phenibut withdrawal, patients were successfully treated with baclofen, benzodiazepines, and phenobarbital, as individual agents or in various combinations. Ancillary medications included antipsychotics, dexmedetomidine, gabapentin, and pregabalin. After stabilization, a number of patients did well on baclofen tapers, whereas others were weaned off benzodiazepines or phenobarbital. Phenobarbital may be preferred over baclofen, or used as an added agent, in patients at risk for seizures. As long as phenibut remains legal, cases of phenibut intoxication and withdrawal are likely to increase. As urine or plasma drug screening for phenibut is not widely available, it is vital that clinicians obtain a detailed medication history in patients presenting to the emergency department with nonspecific symptoms that may represent phenibut intoxication or withdrawal. Further, clinicians may wish to consult an addiction specialist or toxicologist in these situations. [ABSTRACT FROM AUTHOR]

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal‐directed control over reward seeking. Specifically, morphine‐withdrawn rats were impaired in using current reward value to select actions both when relying on prior action‐outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal‐directed action selection. However, brief re‐exposure to morphine was sufficient to impair motivation and disrupt goal‐directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine‐paired context cues and in the absence of response‐contingent feedback. We suggest that these opioid‐withdrawal induced deficits in motivation and goal‐directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use. [ABSTRACT FROM AUTHOR]

Rates of neonatal opioid withdrawal syndrome (NOWS) have been increasing. Acute withdrawal symptoms are well characterized in NOWS infants, but environmental confounds and difficulties in conducting longitudinal studies make it challenging to elucidate potential long-term clinical effects. Preclinical animal models have great utility for studying the persisting consequences of perinatal opioid exposure and to address the mechanistic basis of these effects. Several preclinical perinatal opioid exposure models have been developed. Whereas early animal models primarily used the prototypical opioid, morphine, and a limited opioid exposure period, more recent models have been using various opioid types and different durations of perinatal opioid exposure. Behavioral phenotypes vary across models, reaffirming the importance of dosage, type of opioid, and duration of exposure for the development of specific phenotypes. Neonatal opioid withdrawal syndrome (NOWS) is a growing public health concern. The complexity of in utero opioid exposure in clinical studies makes it difficult to investigate underlying mechanisms that could ultimately inform early diagnosis and treatments. Clinical studies are unable to dissociate the influence of maternal polypharmacy or the environment from direct effects of in utero opioid exposure, highlighting the need for effective animal models. Early animal models of prenatal opioid exposure primarily used the prototypical opioid, morphine, and opioid exposure that was often limited to a narrow period during gestation. In recent years, the number of preclinical studies has grown rapidly. Newer models utilize both prescription and nonprescription opioids and vary the onset and duration of opioid exposure. In this review, we summarize novel prenatal opioid exposure models developed in recent years and attempt to reconcile results between studies while critically identifying gaps within the current literature. [ABSTRACT FROM AUTHOR]

Background: Morphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse. The morphine‐induced increases in neuroinflammation, brain oxidative stress, and alteration of glutamate levels in the hippocampus and nucleus accumbens have been associated with morphine dependence and a higher severity of withdrawal symptoms. Due to its rich content in potent anti‐inflammatory and antioxidant factors, secretome derived from human mesenchymal stem cells (hMSCs) is proposed as a preclinical therapeutic tool for the treatment of this complex neurological condition associated with neuroinflammation and brain oxidative stress. Methods: Two animal models of morphine dependence were used to evaluate the therapeutic efficacy of hMSC‐derived secretome in reducing morphine withdrawal signs. In the first model, rats were implanted subcutaneously with mini‐pumps which released morphine at a concentration of 10 mg/kg/day for seven days. Three days after pump implantation, animals were treated with a simultaneous intravenous and intranasal administration of hMSC‐derived secretome or vehicle, and withdrawal signs were precipitated on day seven by i.p. naloxone administration. In this model, brain alterations associated with withdrawal were also analyzed before withdrawal precipitation. In the second animal model, rats voluntarily consuming morphine for three weeks were intravenously and intranasally treated with hMSC‐derived secretome or vehicle, and withdrawal signs were induced by morphine deprivation. Results: In both animal models secretome administration induced a significant reduction of withdrawal signs, as shown by a reduction in a combined withdrawal score. Secretome administration also promoted a reduction in morphine‐induced neuroinflammation in the hippocampus and nucleus accumbens, while no changes were observed in extracellular glutamate levels in the nucleus accumbens. Conclusion: Data presented from two animal models of morphine dependence suggest that administration of secretome derived from hMSCs reduces the development of opioid withdrawal signs, which correlates with a reduction in neuroinflammation in the hippocampus and nucleus accumbens. [ABSTRACT FROM AUTHOR]

Introduction: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. Methods: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3–5. Results: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. Conclusions: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail. [ABSTRACT FROM AUTHOR]

Background: Crack heroin is a novel opiate derivative with highly addictive properties and unfamiliar health consequences. It causes a variety of brain dysfunctions that are mediated by neurochemical alterations and abnormal neuroplasticity. Brain-derived neurotrophic factor (BDNF) is a widely recognized biological marker implicated in the neuropathology of substance use during substance use disorder and withdrawal. Its involvement can significantly contribute to the severity of withdrawal symptoms. Hence, this study aimed to evaluate BDNF levels in crack heroin users before and after withdrawal. Methods: In this cross-sectional study, 148 male participants were recruited and divided into two groups: persons with crack heroin use disorder (n = 74) and the controls (n = 74). The BDNF serum levels were measured in both crack heroin users and control groups upon hospitalization and again after twenty-one days of withdrawal using the enzyme-linked immunosorbent assay. Results: The results demonstrated that BDNF levels in persons with crack heroin use disorder upon admission were significantly lower than the levels observed upon discharge and in the control group (p < 0.05). Additionally, a significant difference in BDNF levels was found between persons with crack heroin use disorder at admission and discharge (p = 0.038). Furthermore, BDNF levels showed an inverse correlation with the daily dose of substance use (r= -0.420, p = 0.03) and the duration of crack heroin use (r= -0.235, p = 0.001). Conclusions: A progressive increment in BDNF levels during early detoxification is associated with the daily amount of substance use and the duration of substance use. Our findings suggest that changes in BDNF serum levels during crack heroin use disorder and withdrawal could serve as potential biomarkers for assessing the intensity of withdrawal symptoms and substance use-related behaviors. [ABSTRACT FROM AUTHOR]

Detoxification is frequently recommended as a treatment for moderate to severe Cocaine Use Disorder (CUD). However, the response to detoxification varies among patients, and previous studies have focused mostly on patterns of drug use behavior to test associations with treatment outcomes, overlooking the potential impact of psychosocial factors, other clinical variables, and individual life experiences. In this study we comprehensively examined several variables aiming to find the most relevant predictors to classify patients with severe versus non-severe cocaine withdrawal symptoms at the end of detoxification. Methods: Data from 284 women with CUD who enrolled in a 3-week detoxification program was used in this longitudinal study. Psychosocial, clinical, and drug use behavior characteristics were evaluated, generating a dataset with 256 potential predictors. We tested six different machine learning classification algorithms. Results: The best classification algorithm achieved an average accuracy and ROC-AUC of approximately 70%. The 16 features selected as best predictors were the severity of psychiatric, family, and social problems and the level of exposure to childhood maltreatment. Features associated with drug-use behavior included days consuming drugs and having craving symptoms in the last month before treatment, number of previous drug/alcohol-related treatments, and a composite score of addiction severity. The level of cocaine withdrawal syndrome at the beginning of detoxification was also a key feature for classification. A network analysis revealed the pattern of association between predictors. Conclusion: These variables can be assessed in real-world clinical settings, potentially helping clinicians to identify individuals with severe cocaine withdrawal that is likely to be sustained over the course of detoxification. • Machine learning is a promising method to identify patients at high risk of severe withdrawal. • Almost seventy percent of accuracy was achieved by using machine learning. • The top features included drug use behavior, childhood maltreatment, and psychiatric problems. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This systematic review aims to synthesize and summarize the available evidence on the definitions of craving and withdrawal, the nature and presence of withdrawal symptoms, the duration of abstinence, the prevalence and nature of craving. RESULTS: A total of 29 studies met the inclusion criteria. Inconsistencies were revealed in definitions of craving and abstinence, as well as in the specific withdrawal symptoms that might be present among players. Furthermore, there is a predominance of exploration of affective symptoms compared to cognitive and physical symptoms. Mini meta-analyses indicate a significant difference in depression, anxiety, and craving between players with Internet Gaming Disorder (IGD) and regular players. Most studies typically used short-term abstinence, during which participants refrain from specific behaviours for periods ranging from a few days. A majority of studies did not provide information on the occurrence of craving. CONCLUSIONS: Emphasizing craving reduction may alleviate gaming-related withdrawal severity. Longitudinal and qualitative research is essential for understanding craving and withdrawal phenomenology. Bridging the empirical-clinical gap in gaming disorder requires interdisciplinary studies. Investigating prevalent withdrawal symptoms aids in comprehensive research and refined treatments. Prioritizing craving assessment before, during, and after abstinence is crucial. [ABSTRACT FROM AUTHOR]

Epidemiological studies and clinical observations suggest that nicotine, a major contributor of the global burden of disease, acts in a partially sex specific manner. Still, preclinical research has primarily been conducted in males. More research is thus required to define the effects displayed by nicotine on the female brain. To this end, female rats received 15 injections of either nicotine (0.36mg/kg) or saline, over a 3-week period and were then followed for up to 3 months. Behavioral effects of nicotine were assessed using locomotor activity measurements and elevated plus maze, while neurophysiological changes were monitored using ex vivo electrophysiological field potential recordings conducted in subregions of the dorsal and ventral striatum. Behavioral assessments demonstrated a robust sensitization to the locomotor stimulatory properties of nicotine, but monitored behaviors on the elevated plus maze were not affected during acute (24 h) or protracted (3 months) withdrawal. Electrophysiological recordings revealed a selective increase in excitatory neurotransmission in the nucleus accumbens shell and dorsomedial striatum during acute withdrawal. Importantly, accumbal neuroadaptations in nicotine-treated rats correlated with locomotor behavior, supporting a role for the nucleus accumbens in behavioral sensitization. While no sustained neuroadaptations were observed following 3 months withdrawal, there was an overall trend towards reduced inhibitory tone. Together, these findings suggest that nicotine produces selective transformations of striatal brain circuits that may drive specific behaviors associated with nicotine exposure. Furthermore, our observations suggest that sex-specificity should be considered when evaluating long-term effects by nicotine on the brain. [ABSTRACT FROM AUTHOR]

Introduction: Opioid withdrawal is one of the most critical complications of opioid use disorder. In this study, we aimed to examine the possible risk of ventricular arrhythmia and sudden cardiac death by calculating electrocardiography (ECG) changes, the markers of ventricular repolarization, in opioid withdrawal. Methods: A total of 90 patients diagnosed with opioid withdrawal who met the inclusion and exclusion criteria were included in the study. QT, QTc, TPe/QT, and TPe/QTc ratios of patients with a Clinical Opiate Withdrawal Scale (COWS) score higher than five and a Framingham heart risk score lower than 10% were measured in 12-lead ECG. Results: A significant difference was found between the patients' heart rate, QT, QTc, and TPe/QT values during withdrawal (entry-first) and after withdrawal (second) (p<0.05). Mean QT First Value (380.69±22.46) was significantly different and higher than Mean QT Second Value (372.82±19.998); Mean QTc First Value (435.41±16.22) was significantly different and higher than Mean QTc Second Value (418.03±17.79); Mean Tpe First Value (81.62±6.009) was significantly different and higher than Mean Tpe Second Value (79.93±5.524); and The Mean Tpe/QT First Value (0.221±0.005) was significantly different and higher than the Mean Tpe/ QT Second Value (0.213±0.004) (p<0.05). Conclusion: The findings of our study show that electrocardiographic QT, QTc, Tpe and Tpe/QTc values, which indicate the risk of sudden cardiac death and ventricular arrhythmia, are significantly higher during opioid withdrawal. In addition to the regulation of addiction treatment during opioid withdrawal, it should be considered that individuals may be at cardiac risk, and the patient should be monitored for cardiac arrhythmia during the withdrawal period. [ABSTRACT FROM AUTHOR]

Background: Anabolic–androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symptoms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post-cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objective evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms. Methods: An anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they experienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support. Results: The majority of respondents were white, aged 18–30 years old, and working in skilled manual work. 51.7% (n = 243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n = 306) of respondents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessation and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a concern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community. Conclusions: Our survey suggests that the majority of men stopping AAS use are using some form of PCT. Some self-reported symptoms of AAS-induced hypogonadism such as cravings to restart AAS use reduce by 60% and suicidal thoughts reduce by 50%. These individuals are concerned about the negative effect of AAS use and cessation. This study provides crucial information for planning future research to evaluate the effects of PCT on symptoms when men stop AAS use. [ABSTRACT FROM AUTHOR]

Opioid use disorder (OUD) is a critical problem in China and is accompanied by depression and deficits in cognitive control. In China, the most successful intervention for OUD is the community drug rehabilitation where methadone maintenance treatment (MMT) plays a key role. Even though methadone for the treatment of OUD can be helpful, it can cause severe somatic side‐effects, which limit its effectivity. Even worse, it can have detrimental effects on cognitive control, which is crucial to regain control over drug intake. Here, we consider the potential use of auricular transcutaneous vagus nerve stimulation (atVNS) as an addition to MMT for opioid withdrawal treatment. Compared to other non‐invasive brain stimulation methods, atVNS also targets the locus coeruleus (LC) important for noradrenaline (NA) synthesis. NA is an essential neurotransmitter impacted in opioid withdrawal and also critically involved in cognitive control processes. Its ADD‐ON to MMT might be a useful mean to improve mood and enhance cognitive control processes impacted in OUD. We discuss the translational advantages of atVNS in China such as the cultural acceptance of the modality of treatment similar to electroacupuncture. Additionally, the wearability of the ear electrode and at‐home self‐administration without intense medical supervision makes of atVNS a useful tool to enhance clinical and cognitive outcomes especially in everyday life situation. We discuss how atVNS can be integrated in tele‐medical health approaches allowing that innovative treatments can widely be disseminated and continued even in situations of restricted medical access. [ABSTRACT FROM AUTHOR]

The author comments on a review of researches which show a low level of precipitated withdrawal with buprenorphine induction to treat opioid use disorder (OUD) in 2025. Topics covered include synthetic fentanyl's involvement in overdose deaths, and the treatment of opioid withdrawal by buprenorphine and methadone. Also noted is the possible successful treatment of OUD when there is a low likelihood of precipitated withdrawal.

Introduction: Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Methods: Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). Results: CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-lβ and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R² = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). Discussion: The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. Trial registration: ClinicalTrials.gov, identifier: NCT# 00106106. [ABSTRACT FROM AUTHOR]

Cannabis use disorder (CUD) presents differently in men and women, particularly in symptoms of cannabis withdrawal. Novel pharmacotherapeutic interventions for CUD, such as those that target the endocannabinoid (eCB) system, must be developed in a manner consistent with these sex differences. The present pilot study sought to prospectively assess sex differences in cannabis withdrawal in a small sample of adults with moderate‐to‐severe CUD and to determine if withdrawal was associated with peripheral eCB and eCB congener tone. Men and women (n = 5/sex) completed 2 weeks of study participation separated by 1 month; in the latter week, participants abstained from cannabis use. Each week, participants attended in‐person laboratory visits during which blood was drawn repeatedly to assess plasma eCB and eCB congener tone. Participants also completed multiple daily ambulatory assessments to assess cannabis use and withdrawal symptoms. As anticipated, women reported a greater increase in withdrawal symptoms during the abstinent week [Δ = 9.4 (SE = 1.1); p < 0.001] than men [Δ = 1.2 (SE = 1.2); p = 0.35]. Sex differences in levels of the eCB N‐arachidonoylethanolamide (AEA), as well as the eCB congeners stearoylethanolamide (SEA) and linoleylethanolamide (LEA), were evident during abstinence at the morning time point only (p's < 0.05). LEA was associated with withdrawal symptom expression in both sexes [β = 0.16 (SE = 0.09)] and palmitoylethanolamide (PEA) [β = 0.22 (SE = 0.13)] and 2‐arachidonoylglycerol (2‐AG) [β = 0.32 (SE = 0.15)] were associated with withdrawal symptoms in women only. Pharmacotherapeutic development for CUD should consider evident sex differences in eCB and eCB congener tone during abstinence and their associations with cannabis withdrawal, as eCB‐based interventions may produce differential effects by sex. [ABSTRACT FROM AUTHOR]

As the accurate and sensitive measurement of withdrawal constitutes a crucial component of detoxification, there is a need to apply a recovery-oriented lens and critical review to substance withdrawal tools. Adhering to PRISMA guidelines and applying a recovery-oriented lens, I conducted a critical interpretive synthesis on articles that used substance withdrawal tools published in the Journal of Substance Use. I used a recovery-oriented lens to critically assess the strengths and limitations of the substance withdrawal tools. A total of 10 studies met eligibility criteria. These 10 studies used 13 different tools to measure withdrawal. Results of the analysis indicated that most tools were relatively brief, were substance-specific, did not contain subscales, and framed items in a negative manner. Perhaps most noteworthy, the tools were not created with input from service users. The diminutive number of studies measuring withdrawal is indicative of a consequential gap in the literature. While most withdrawal tools contained relatively few items, they should be substance-specific and contain subscales to assess multiple domains. There is a need for service user involvement in the design of withdrawal tools. Implications for clinical practice, limitations of the study, and suggestions for future research are provided. [ABSTRACT FROM AUTHOR]

Experts recommend using the lowest effective dose of naloxone to balance the reversal of opioid-induced respiratory depression and avoid precipitated opioid withdrawal, however, there is no established dosing standards within the emergency department (ED). The aim of this review was to determine current naloxone dosing practice in the ED and their association with adverse events. We conducted a systematic review by searching PubMed, Cochrane, Embase, and EBSCO from 2000–2021. Articles containing patient-level data for initial ED dose and patient outcome had data abstracted by two independent reviewers. Patients were divided into subgroups depending on the initial dose of i.v. naloxone: low dose ([LD], < 0.4 mg), standard dose ([SD], 0.4–2 mg), or high dose ([HD], > 2 mg). Our outcomes were the dose range administered and adverse events per dose. We compared groups using chi-squared difference of proportions or Fisher's exact test. The review included 13 articles with 209 patients in the results analysis: 111 patients in LD (0.04–0.1 mg), 95 in SD (0.4–2 mg), and 3 in HD (4–12 mg). At least one adverse event was reported in 37 SD patients (38.9%), compared with 14 in LD (12.6%, p < 0.0001) and 2 in HD (100.0%, p = 0.16). At least one additional dose was administered to 53 SD patients (55.8%), compared with 55 in LD (49.5%, p < 0.0001), and 3 in HD (100.0%, p = 0.48). Lower doses of naloxone in the ED may help reduce related adverse events without increasing the need for additional doses. Future studies should evaluate the effectiveness of lower doses of naloxone to reverse opioid-induced respiratory depression without causing precipitated opioid withdrawal. [ABSTRACT FROM AUTHOR]

Mitragyna speciosa or Kratom has been used in Thailand traditionally for its medicinal value. Despite case reports of kratom consumption causing adverse effects, research on its long-term health impact is limited. This study examines the long-term health impact of kratom use among people in Southern Thailand. Three community-based surveys were conducted from 2011 to 2015. In the first and second surveys (2011 and 2012) a total of 1,118 male respondents comprising 355 regular kratom users, 171 occasional kratom users, 66 ex-users, and 592 non-users aged 25 or above, were recruited from 40 villages. All respondents were followed up in this study. However, not all respondents were successfully followed up throughout the entire set of studies. Common health complaints were no more common among kratom users than ex- and non-users, but more regular than occasional users claimed kratom to be addictive. Those with high kratom dependence scores were more likely to experience intense withdrawal symptoms, which developed 1-12 h after the last kratom intake. Over half (57.9%) of regular users had experienced intoxication effects compared to only 29.3% of occasional users. Kratom users were less likely to have a history of chronic diseases such as diabetes, hypertension, dyslipidemia than ex- and non-users. Regular long-term chewing of fresh kratom leaves was not related to an increase in common health complaints, but may pose a drug dependence risk. Severe kratom dependents were more likely to suffer from intense withdrawal symptoms. Medical records revealed no death due to traditional kratom use, but the high prevalence of tobacco or/and hand rolled cigarette smoking among kratom users should be of concern. [ABSTRACT FROM AUTHOR]

To measure the association of baseline psychological symptoms (depressive symptoms and perceived stress) with withdrawal from a cohort study. Depressive symptoms and perceived stress were obtained using validated measures during the baseline computer-assisted telephonic interview for the REasons for Geographic and Racial Differences in Stroke study a national longitudinal cohort (≥45 years, 42% Black, 55% women) recruited between 2003 and 2007. Participants who completed follow-up after September 1, 2019, were considered active. Primary outcome was time to study withdrawal. The association of psychological symptoms and time-to-withdrawal was measured using Cox proportional hazard regression models with incremental adjustments by demographic and clinical factors. Out of 29,964 participants included in the analysis, 11,111 (37.1%) participants withdrew over the follow-up period (median: 11 years). Compared to participants with low depressive symptoms, those with moderate symptoms had 5% higher risk (aHR= 1.05; 95% CI= 1.00-1.10) and those with high level of depressive had 19% higher risk (aHR= 1.19; 95% CI= 1.11-1.27) of withdrawal in fully adjusted models. No significant association between perceived stress and withdrawal risk was observed. Depressive symptoms were significantly associated with withdrawal. Prevalence of depressive symptoms at baseline is an important indicator of participant retention in large prospective cohorts. [ABSTRACT FROM AUTHOR]

Introduction: Infants exposed to opioids in utero are at high risk of exhibiting Neonatal Opioid Withdrawal Syndrome (NOWS), a combination of somatic withdrawal symptoms including high pitched crying, sleeplessness, irritability, gastrointestinal distress, and in the worst cases, seizures. The heterogeneity of in utero opioid exposure, particularly exposure to polypharmacy, makes it difficult to investigate the underlying molecular mechanisms that could inform early diagnosis and treatment of NOWS, and challenging to investigate consequences later in life. Methods: To address these issues, we developed a mouse model of NOWS that includes gestational and post-natal morphine exposure that encompasses the developmental equivalent of all three human trimesters and assessed both behavior and transcriptome alterations. Results: Opioid exposure throughout all three human equivalent trimesters delayed developmental milestones and produced acute withdrawal phenotypes in mice reminiscent of those observed in infants. We also uncovered different patterns of gene expression depending on the duration and timing of opioid exposure (3-trimesters, in utero only, or the last trimester equivalent only). Opioid exposure and subsequent withdrawal affected social behavior and sleep in adulthood in a sex-dependent manner but did not affect adult behaviors related to anxiety, depression, or opioid response. Discussion: Despite marked withdrawal and delays in development, long-term deficits in behaviors typically associated with substance use disorders were modest. Remarkably, transcriptomic analysis revealed an enrichment for genes with altered expression in published datasets for Autism Spectrum Disorders, which correlate well with the deficits in social affiliation seen in our model. The number of differentially expressed genes between the NOWS and saline groups varied markedly based on exposure protocol and sex, but common pathways included synapse development, the GABAergic and myelin systems, and mitochondrial function. [ABSTRACT FROM AUTHOR]

The article addresses several issues regarding the treatment of phenibut withdrawal. Topics include the inaccuracy of statements about baclofen's safety in withdrawal management, the need for different treatment strategies for tapering versus abstinence, and concerns over the suggested dosing regimen for baclofen in comparison to phenibut.

It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non‐randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2–4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal. [ABSTRACT FROM AUTHOR]

Purpose: Fentanyl, a highly potent synthetic opioid used in cancer and non-cancer pain, is approved for various routes of administration. In Europe, fentanyl consumption increased substantially in the last decades but information on abuse, dependence and withdrawal associated with fentanyl is scarce, especially with respect to its different formulations. Methods: We analysed case characteristics of spontaneous reports of suspected fentanyl-associated abuse, dependence or withdrawal from European countries recorded in the EudraVigilance database up to 2018 with respect to the (designated) routes of administration and potential indications. Results: A total of 985 reports were included (mainly from France and Germany) with 43% of cases referring to transdermal fentanyl. Median age was 45 years (48.8% female) and 21.6% had musculoskeletal disorders. Only 12.6% of those using transdermal fentanyl had a cancer diagnosis compared to 40.2% and 26.8% of those using intranasal and oral transmucosal fentanyl, respectively. Depression was common (10.7%) and highest in cases with musculoskeletal disorders (24.9%) as was the use of benzodiazepines. Overall, 39.5% of reports resulted in a prolonged hospital stay and for 23.2% a fatal outcome was recorded. The respective proportions were especially high in cases with musculoskeletal disorders (56.3% with prolonged hospitalisation) and in those using transdermal fentanyl (35.2% fatalities). Conclusions: In suspected cases of abuse, dependence or withdrawal, fentanyl was mainly used for non-cancer pain indications and most often as transdermal formulations. Depression and prolonged hospitalisations were common, especially in patients with musculoskeletal disorders, indicating a vulnerable patient group and complex treatment situations. [ABSTRACT FROM AUTHOR]

Background: Withdrawal from addictive drugs can be reduced by administering placebo deceptively, but in the clinic it is unethical to deceive the patient. Open-label placebo effects have been observed across a range of psychophysiological phenomena, and may also apply to drug withdrawal. Method: 24-hour abstinent heavy coffee drinkers (N = 61) rated their caffeine withdrawal symptoms before being allocated to one of three groups. The Deceptive group was given decaffeinated coffee (decaf) and told it was caffeinated, the Open-Label group given decaf and told it was decaf and the Control group given water and told it was water. After 45 min, caffeine withdrawal was measured again. All participants rated their expectancies of withdrawal reduction from caffeinated coffee, decaf and water prior to being randomised and the end of the study. Results: There was a significant 9.5-point reduction in caffeine withdrawal in the Open-Label group (95% confidence interval (CI): 4.7, 14.3; p = 0.002), which was 8.6 points less than the Deceptive group (95%CI: 0.4, 16.8; p = 0.014) but 8.9 points greater than the Control group (95%CI: 0.6, 17.2; p = 0.012). Pre-randomisation, participants expected caffeinated coffee to reduce their withdrawal symptoms the most, followed by water and decaf, Pre-randomisation expectancy of withdrawal was only associated with amount of withdrawal reduction in the Deceptive group. Conclusion: It appears as if open-label placebo caffeine (i.e. decaf) can reduce caffeine withdrawal symptoms, even when people do not hold a conscious expectancy it will do so. There may be ways to integrate open-label placebo procedures into clinical interventions for drug dependence without violating informed consent. [ABSTRACT FROM AUTHOR]

• Standard dose naloxone is 0.4 mg intramuscular (IM) or ≤4 mg intranasal (IN). • high dose and long-acting opioid antagonists have no use in overdose response. • people who use drugs should be involved in opioid antagonist development. • harm reduction programs can teach rescue breathing to mitigate withdrawal risk. • withdrawal should be carefully considered in opioid antagonist product selection. High dose and long-acting opioid overdose reversal drugs can precipitate withdrawal in people who are opioid dependent. Products recently brought to market for community use in the United States (US) have drawn international concern because of their increased risk of withdrawal. At the March 18–19, 2024, Compassionate Overdose Response Summit & Naloxone Dosing Meeting, a panel of harm reduction experts issued the following call to action: 1) people who use drugs should be directly involved in decisions regarding the research, development, selection, and distribution of opioid overdose reversal products; 2) regulatory agencies and pharmaceutical manufacturers should carefully consider and communicate the risk and duration of withdrawal associated with higher dose and longer-acting opioid antagonists; 3) take-home naloxone kits should include at least two doses of an intramuscular (IM) product containing 0.4 mg or an intranasal (IN) product containing ≤4 mg; 4) At this time, high dose and long-acting opioid antagonists have no use in acute opioid overdose response; and, 5) overdose response educational materials, instructions on overdose response, and training should emphasize the restoration of breathing, avoiding withdrawal, and compassionate post-overdose support and care. High dose and long-acting opioid overdose reversal drugs were approved without testing for withdrawal and are often aggressively marketed despite decades of evidence from naloxone distribution programs worldwide that the ideal dose of naloxone is one that restores breathing without inducing withdrawal. Government agencies should direct resources to harm reduction programs to make standard dose take-home naloxone products widely available among people who use drugs. Lay bystanders, people who use drugs, their families, and professional first responders can learn and apply a compassionate approach to opioid overdose response. [ABSTRACT FROM AUTHOR]

Background: For patients with opioid use disorder, buprenorphine extended-release injection (BUP-XR) achieves sustained therapeutic plasma concentrations, controls craving and withdrawal symptoms, and improves patient outcomes. Given retention challenges during transmucosal buprenorphine (BUP-TM) induction, assessing methods to quickly achieve sustained buprenorphine concentrations is important. Objectives: This open-label, single-group, single-center pilot study (NCT03993392) evaluated safety and tolerability of initiating BUP-XR following a single BUP-TM 4 mg dose. Methods: Eligible participants abstained from short and long-acting opioids for 6 and 24 hours, respectively. If the Clinical Opiate Withdrawal Scale (COWS) was ≥8, BUP-TM 4 mg was administered. Participants not exhibiting hypersensitivity, precipitated opioid withdrawal (POW), or sedation symptoms within 1 hour received BUP-XR 300 mg (assessed as inpatients for 48 hours and outpatients to Day 29). Endpoints were COWS score increase ≥6, independent adjudication of POW, and opioid use. Results: Twenty-six participants (14 male) received BUP-TM, 24 received BUP-XR, and 20 completed the study. After injection, COWS scores decreased from pre-BUP-TM baseline of 14.6 ± 4.1 to 6.9 ± 4.1 at 6 hours and 4.2 ± 3.2 at 24 hours. Most participants (62.5%) experienced maximum COWS scores pre-BUP-XR; 2 experienced a COWS score increase ≥6, occurring at 1 and 2 hours post-BUP-XR. By adjudication, 2/24 participants experienced POW. Irritability, anxiety, nausea, and pain were the most frequent adverse events (AEs) with no serious AEs. Conclusions: Results support increased flexibility for initiating BUP-XR. Initiating BUP-XR 300 mg following a single BUP-TM 4 mg dose was well tolerated. Although some participants initially experienced withdrawal symptoms after injection, significant symptomatic improvement was observed in all participants within 24 hours. [ABSTRACT FROM AUTHOR]

Rationale: Regular consumption of gamma-hydroxybutyrate (GHB) may result in a dependence syndrome that can lead to withdrawal symptoms. There are limited data on medications to manage GHB withdrawal. Objectives: To examine characteristics associated with delirium and discharge against medical advice (DAMA), in the context of implementing a GHB withdrawal management protocol at an inner-city hospital in 2020. Methods: We retrospectively reviewed records (01 January 2017–31 March 2021), and included admissions that were ≥ 18 years of age, admitted for GHB withdrawal, and with documented recent GHB use. Admissions were assessed for demographics, medications administered, features of delirium, ICU admission, and DAMA. Exploratory analyses were conducted to examine factors associated (p < 0.2) with features of delirium and DAMA. Results: We identified 135 admissions amongst 91 patients. Medications administered included diazepam (133 admissions, 98.5%), antipsychotics (olanzapine [70 admissions, 51.9%]), baclofen (114 admissions, 84%), and phenobarbital (8 admissions, 5.9%). Features of delirium were diagnosed in 21 (16%) admissions. Delirium was associated with higher daily GHB consumption prior to admission, while duration of GHB use, time from presentation to first dose of diazepam, and concomitant methamphetamine use were inversely associated with delirium. DAMA occurred amongst 41 (30%) admissions, and was associated with a longer time from presentation to first dose of baclofen, while being female and receiving a loading dose of diazepam were inversely associated. Conclusions: This study adds to the literature in support of the safety and feasibility of diazepam and baclofen for the management of GHB withdrawal. Prospective, randomised trials are required. [ABSTRACT FROM AUTHOR]

Issues: Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta‐analysis since 2008. Approach: MEDLINE (1966–2020), CINAHL (1982–2020), PsychINFO (1806–2020) and EMBASE (1947–2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta‐analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted. Key Findings: Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta‐analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD −0.49, 95% CI −0.80, −0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established. Conclusions: There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high‐quality trials. [ABSTRACT FROM AUTHOR]

Introduction: Alcoholism, also known as alcohol use disorder (AUD), is a broad term for any drinking of alcohol that results in mental or physical health problems like anxiety, dependence and depression. This study was conducted with aim to determine association between alcohol dependence and depressive episode before and after treatment for alcohol dependence. Methods and Materials: An observational study was conducted among all diagnosed alcohol dependent and depressed adult patients attending to Psychiatry OPD of a Medical College in Kolkata for a period of one year. Baseline assessment was done during first visit with a semi structured questionnaire for socio-demographic profile and using AUDIT, CIWA and HAM-D 17 scale for their mental status and further assessments on day 14, day 30, after 2 months using same scales. Relationship between depression with alcohol dependence were determined by Pearson corelation test and presented with tabular form and scatter plot. Changes in mean score of different scales before and after treatment was assessed by paired t test considering confidence interval (CI) of 95% and p value = 0.05 as significant. Result: Out of 70 patients, almost 90% of them were below the age 45 years with male preponderance (94.3%). Paired t test result showed, association of mean scores of different scales, before and after treatment of dependence was statistically significant (p=0.00). Mean AUDIT score, mean CIWA score and mean HAM score for the patients were found to be decreased with advancement of treatment. Pearson correlation test revealed, moderate relationship between AUDIT score and HAMD17 score (0.522) and strong relationship between AUDIT score and CIWA score (0.789). Conclusion: If alcohol dependence is treated properly there will be automatically decreased prevalence of alcohol withdrawal and alcohol induced depressive episodes. [ABSTRACT FROM AUTHOR]

Alcoholism affects about 2 billion people worldwide. Withdrawal causes a neuroinflammatory response that increases anxiety. α-tocopherol is the most important antioxidant that has its in vivo action currently known. Therefore, this study aimed to evaluate the effect of α-tocopherol on the neuroinflammatory process in brain regions involved in anxiety and its anxiolytic potential during alcohol withdrawal. For this, male Wistar rats were divided into four groups and submitted to a procedure of forced and chronic self-administration of liquid diet containing 6% and 8% ethanol for 15 days, followed by abrupt interruption of treatment. Animals in the control group received the liquid diet without ethanol. Twenty-four or 48 h after ethanol discontinuation, and 30 min after the last administration of α-tocopherol or saline, animals were evaluated in the elevated plus maze, light/dark box, and open field tests. At the end of the tests, each experimental group underwent brain tissue collection for analysis of cytokine levels. The results showed that: alcohol induces the neuroinflammatory process and anxiety; the stress generated by withdrawal can induce oxidative stress, which alters the production of inflammatory cytokines in the amygdaloid nuclei (AN) and medial hypothalamic nucleus (mHN); α-tocopherol exhibited anxiolytic and anti-inflammatory activity, attenuating the anxious behavior of abstinent animals and reducing neuroinflammation in AN and mHN; and the intensity of the anxiolytic and anti-inflammatory effect of α-tocopherol is dose-dependent. These results identify α-tocopherol as a potential therapeutic target supporting the fight against relapse during alcohol withdrawal. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) do not discriminate. Anyone can be affected regardless of age, sex, ethnicity, socioeconomic status, or profession. Nurses with SUDs present serious risks to both their patients and the nursing profession. Frontline nurses' responsibility to provide patients with safe, high-quality care may be too great a challenge for those with SUDs, resulting in adverse consequences. Early recognition and treatment of nurses with SUDs promotes patient safety and retention in the profession. For this reason, all nurses and other health care professionals should be able to recognize behaviors associated with SUDs and should be familiar with the available treatment modalities. A guide to early recognition, diagnosis, and treatment of substance-related disorders among colleagues in the workplace. [ABSTRACT FROM AUTHOR]

A qualitative descriptive study was conducted concurrent with a larger study investigating the effects of hyperbaric oxygen treatment on withdrawal symptoms for adults receiving daily methadone for opioid use disorder. The aims of this study were to (a) evaluate the perceptions of withdrawal symptoms and sleep characteristics of study participants and (b) explore the experiences of participation in the parent trial of hyperbaric oxygen treatment. Adults with opioid use disorder can experience distressing symptoms related to withdrawal as well as co-occurring symptoms; sleep impairment is frequently reported. Few studies have examined how adults who receive medication for opioid use disorder experience sleep. A preliminary study of adults receiving daily methadone found that withdrawal symptoms were improved after hyperbaric oxygen treatment. This study explores the narrative of opioid users who report their overall experiences with withdrawal and sleep as well as their experiences of hyperbaric therapy. A convenience sample of six participants was recruited, who represented a small subgroup of participants who completed the larger hyperbaric treatment study. Data were collected via semistructured interviews. Data were analyzed using the qualitative content analysis guidelines proposed by Schreier (2012). All participants described poor overall sleep hygiene and disturbed sleep. More than half of the respondents reported improved or eliminated withdrawal symptoms, and all reported improvement in sleep quality after participation in the sleep study. This companion study confirms that subjective sleep disturbance may be prevalent for adults with opioid use disorder. Participants felt the experience of hyperbaric oxygen treatment produced a positive effect on sleep. [ABSTRACT FROM AUTHOR]

Background: Cannabis-related medical consultations are increasing worldwide, a non-negligible public health issue; patients presenting to acute care traditionally complain of abdominal pain and vomiting. Often recurrent, these frequent consultations add to the congestion of already chronically saturated emergency department(s) (ED). In order to curb this phenomenon, a specific approach for these patients is key, to enable appropriate treatment and long-term follow-up. Objectives: This study reviews cannabinoid hyperemesis syndrome (CHS) and cannabis withdrawal syndrome (CWS), in a bid to help promote better understanding and handling of pathologies associated with chronic cannabis use. Following a literature review, we present a novel therapeutic algorithm aimed at guiding clinicians, in a bid to improve long-term outcomes and prevent recurrences. Methods: Using the keywords "Cannabis," "Hyperemesis," "Syndrome," "Withdrawal," and "Emergency Medicine," we completed a literature review of three different electronic databases (PubMed®, Google scholar®, and Cochrane®), up to November 2021. Results: Although often presenting with similar symptoms such as abdominal pain and vomiting, cannabinoid hyperemesis syndrome (CHS) and cannabis withdrawal syndrome (CWS) are the result of two differing pathophysiological processes. Distinguishing between these two syndromes is essential to provide appropriate symptomatic options. Conclusion: The correct identification of the underlying cannabis-related syndrome, and subsequent therapeutic choice, may help decrease ED presentations. Our study emphasizes the importance of both acute care and long-term outpatient follow-up, as key processes in cannabis-related disorder treatment. [ABSTRACT FROM AUTHOR]

Maternal opioid use is a well-known cause of neonatal opioid withdrawal syndrome (NOWS). Pregnant women may seek non-opioid alternatives to manage opioid dependence to avoid NOWS. Kratom is a psychoactive herbal supplement with opioid activity and is marketed as a non-opioid remedy for opioid withdrawal. Many health care professionals are still unaware of kratom use and availability. Kratom is undetectable by standard drug screens. Neonates are withdrawing and developing NOWS when their mother's history is positive for kratom use. We present two NOWS cases secondary to maternal kratom exposure. Both neonates developed withdrawal signs and symptoms within the first 36 hours of life. Subsequently, they were successfully treated with methadone. Awareness of the effects of maternal use of kratom is essential for better care for neonates by both pregnant women and healthcare providers. [ABSTRACT FROM AUTHOR]

The assessment of opioid withdrawal symptoms is common in both clinical and research settings. The Clinical Opiate Withdrawal Scale (COWS) is among the most frequently used instruments for the assessment of signs and symptoms associated with opioid withdrawal. The COWS is a validated, clinician-administered instrument initially developed and validated for English-speaking populations. To date, however, the COWS has yet to be linguistically and culturally adapted for French-Canadian populations. Objective: The main objective of the present study was to develop a French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) for the assessment of opioid withdrawal symptoms in clinical and research settings. Methods: The French-Canadian translation and cultural adaptation of the COWS was performed following guidelines for the translation and cross-cultural adaptation of self-report measures. The steps consisted of (1) initial translation from English to French, (2) synthesis of the translation, (3) back-translation from French to English, (4) expert committee meeting, (5) test of the prefinal version among healthcare professionals and (6) review of final version by the expert committee. The expert committee considered four major areas where the French-Canadian version should achieve equivalence with the original English-version of the COWS. These areas were (1) semantic equivalence; (2) idiomatic equivalence; (3) experiential equivalence and (4) conceptual equivalence. Results: Rigorous steps based on the guidelines for the translation and cultural adaptation of assessment tools were followed, which led to a semantically equivalent version of the COWS. After a pretest among healthcare professionals, members from the expert committee agreed upon slight modifications to the French-Canadian version of the COWS to yield a final COWS-FC version. Conclusions: A French-Canadian translation and adaptation of the COWS (i.e., the COWS-FC) was developed. The COWS-FC could be used for the assessment of opioid withdrawal symptoms in clinical and research settings. [ABSTRACT FROM AUTHOR]

SUMMARY: We now recognise that withdrawal symptoms from antidepressants are common, and can be severe and long-lasting in some people. Many withdrawal symptoms overlap with symptoms of anxiety or depression, making it difficult to distinguish withdrawal from relapse. We describe how their onset soon after dose reduction, the association of psychological with physical symptoms, their prompt response to reinstatement, and their typical 'wave' pattern of onset, peak and resolution can help distinguish withdrawal symptoms from relapse. We also examine evidence that suggests that antidepressant withdrawal symptoms are misdiagnosed as relapse in discontinuation studies aimed at demonstrating the ability of antidepressants to prevent future relapse (relapse prevention properties). In these discontinuation studies people have their antidepressants stopped abruptly, or rapidly, making withdrawal symptoms very likely, and little effort is made to measure withdrawal symptoms or distinguish them from relapse. We conclude that there is currently no robust evidence for the relapse prevention properties of antidepressants, and current guidance might need to be re-evaluated. [ABSTRACT FROM AUTHOR]

The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan for dose adjustment is usually done as per drug information recommendations from the licensing bodies, but there are no clear guidelines with regards to the best practice regarding the tapering off schedule given sudden dose reductions of drugs such as dopamine agonists may have serious adverse consequences. A systematic literature search was, therefore, performed to derive recommendations and the data show that there are no controlled studies or evidence-based recommendations how to taper or discontinue PD medication in a systematic manner. Most of the data were available on the dopamine agonist withdrawal syndrome (DAWS) and we found only two instructions on how to reduce pramipexole and rotigotine published by the EMA. We suggest that based on the available data, levodopa, dopamine agonists (DA), and amantadine should not be discontinued abruptly. Abrupt or sudden reduction of DA or amantadine in particular can lead to severe life-threatening withdrawal symptoms. Tapering off levodopa, COMT inhibitors, and MAO-B inhibitors may worsen motor and non-motor symptoms. Based on our clinical experience, we have proposed how to reduce PD medication and this work will form the basis of a future Delphi panel to define the recommendations in a consensus. [ABSTRACT FROM AUTHOR]

Infective endocarditis is a potentially fatal infection of the endocardium or valves that can result from IV drug abuse. This article describes a patient with infective endocarditis masked by opioid abuse withdrawal symptoms. This challenging presentation brings to the forefront the need for clinicians to be aware of and understand the changing risk factors and demographics of patients with nonspecific infective endocarditis. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the potential effect of vitamin B 12 (Vit B 12) on cognition impairment caused by nicotine (Nic) cessation in adolescent male rats. Adolescent male rats were categorized into two main groups as vehicle (normal saline, intraperitoneally), and Nic group in which received Nic (2 mg/kg) from 21 to 42 days of ages and then the Nic group were divided into three groups as withdrawal (the animals returned to regular diet without treatment), second and third groups received bupropion (20 mg/kg), and Vit B 12 at three different doses including 0.5,1, and 1.5 mg/kg by oral gavage as treatments to attenuate Nic withdrawal symptoms. The last group including normal animals received the highest doses of Vit B 12 just in the Nic abstinence period to compare the effect of that with vehicle. In MWM, Vit B 12 and bupropion increased the time spent in the target quadrant that is strongly associated with spatial memory as well as the more time spent with the NORT. Vit B 12 and bupropion modulated both oxidant/antioxidant and inflammatory/anti-inflammatory balance, alongside inhibitory effect on AChE, and GFAP. However, BDNF and amyloid-B showed insignificant difference as compared to Vit B 12 and bupropion. Considering the present results and similar related studies, Vit B 12 can be introduced as a strong anti-oxidant, and anti-inflammatory agent by which probably improved memory impairment caused by Nic addiction accompanied by withdrawal. Further, other mechanisms including activity reduction of AChE, and GFAP should be considered; however, it needs further investigation and larger-scale evidences. [Display omitted] [ABSTRACT FROM AUTHOR]

Patients with opioid use disorder (OUD) are commonly admitted to various inpatient services where treatment can be started. The typical initiation of buprenorphine involves delay of treatment until withdrawal symptoms occur, however, those symptoms may interfere with other medical therapy. The purpose of this study was to evaluate the safety and efficacy of initiation of buprenorphine for inpatients with OUD. We reviewed the charts of 99 patients for whom the inpatient addiction medicine consult service was contacted over a 15-month period from January 2020 to identify those patients started on buprenorphine. We abstracted data on toxicology results, prior use of buprenorphine, and Clinical Opioid Withdrawal Scale (COWS) and pain scores before and after the administration of buprenorphine. There was no significant difference in COWS classification post treatment based on ancillary or non use of full agonist therapy. There was no significant change in COWS scores based on prior buprenorphine or methadone use. 5% of patients developed moderate withdrawal (COWS score 12–24) after the initiation of buprenorphine. Twenty of the study patients (20%) developed a 2-point increase in pain scores after the initiation of buprenorphine. The initiation of buprenorphine for inpatients rarely results in a significant increase in withdrawal symptoms. A larger percent of patients may have an increase in pain scores which would need to be managed. Further prospective work on this subject is warranted. [ABSTRACT FROM AUTHOR]

Statement of the Problem: As a stimulant drug of the central nervous system, methamphetamine reduces salivary secretion by stimulating inhibitory α2-receptors in the sympathetic system. The acidity of this substance reduces the salivary pH and causes severe dental caries and erosion in the cervical region of teeth, appearing as "meth mouth". Purpose: This study aimed to determine the effects of methamphetamine withdrawal on the volume and pH of stimulated saliva in patients under treatment at rehabilitation centers. Materials and Method: This descriptive cross-sectional study was conducted on a total of 20 individuals at the rehabilitation centers of Gorgan, Iran. The volume and pH of stimulated saliva were measured at three intervals: before withdrawal, four days after withdrawal, and 30 days after withdrawal. Data analysis was performed using ANOVA test in SPSS. Results: The results showed a significant difference in the mean volume of saliva before and after withdrawal (p< 0.05). Thirty days after withdrawal, the mean volume of saliva was significantly different from the mean volume after four days (p< 0.05). Moreover, the mean pH of saliva after withdrawal was significantly different from the mean pH before withdrawal (p< 0.001). On the other hand, the mean salivary pH at 30 days after withdrawal was not significantly different from the mean pH on the fourth day after withdrawal (p> 0.05). Conclusion: It seems that methamphetamine withdrawal influences the volume and pH of stimulated saliva in patients under treatment at rehabilitation centers. [ABSTRACT FROM AUTHOR]

Benzodiazepines continue to be prescribed widely in the management of patients with insomnia or anxiety disorders, despite the availability and acceptability of alternative pharmacological and psychological treatments. Many patients will experience adverse effects during treatment and considerable distress when the dosage is reduced and stopped. Management of benzodiazepine withdrawal includes measures to prevent the development of dependence, careful attention to underlying medical conditions, medication consolidation and gradual dosage reduction, accompanying psychological interventions, occasional prescription of concomitant medication, and relapse prevention with on‐going support to address psychosocial stressors. There are needs for easier patient access to services with refined expertise and for further research to optimise strategies for preventing dependence and facilitating withdrawal. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11–50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p's < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis. [ABSTRACT FROM AUTHOR]

Craving and withdrawal can contribute to the development and maintenance of substance use disorder (SUD), relapse, and overdose. Although music therapy can positively impact craving and withdrawal in adults with SUD on a detoxification unit, there is a lack of randomized research comparing different music therapy interventions as well as studies measuring within-session changes in these critical constructs. The purpose of this effectiveness study was to compare motivational-educational songwriting (MESW) and recreational music therapy (RMT) via measures of craving and withdrawal in adults with SUD on a detoxification unit using a two-group pre- and posttest design. Participants (N = 134) were cluster-randomized to a single group MESW or RMT condition. Established craving and withdrawal psychometric instruments were used as pre- and posttests to determine potential within- and between-group differences. There were significant within-group differences in craving subscales of urges and coping as well as withdrawal, all p <.001. Within-group effect sizes ranged from.244 to.456 with favorable changes from pre- to posttest. There was no between-group difference among the MESW and RMT conditions, all p >.05. Although the specific music therapy intervention did not impact craving or withdrawal, a single MESW or RMT session can have an immediate and significant positive impact on craving and withdrawal in adults with SUD on a detoxification unit. As the MESW condition also addressed motivational and educational aspects of recovery, perhaps MESW interventions are ideal in detoxification settings. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) may represent a promising therapeutic tool for treating opioid use disorder (OUD). This study was aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous heroin withdrawal. Thirty hours after cessation of 8-day heroin treatment (5, 10, 20 and 40 mg·kg-1 /12 h; s.c.), spontaneous heroin withdrawal was evaluated in CD1 male mice. The effects of CBD (5, 10 and 20 mg·kg-1 ; i.p.) on withdrawal-related behaviour were evaluated by measuring anxiety-like behaviour, motor activity and somatic signs. Furthermore, gene expression changes of mu-opioid receptor (Oprm1), proopiomelanocortin (Pomc), cannabinoid CB1 (Cnr1) and CB2 (Cnr2) receptors in the nucleus accumbens (NAcc) and tyrosine hydroxylase (TH) and Pomc in the ventral tegmental area (VTA) were also evaluated by real-time PCR. Anxiety-like behaviour, motor activity and withdrawal-related somatic signs were significantly increased in heroin-treated mice compared to the control group. Interestingly, CBD treatment significantly reduced these behavioural impairments and normalized gene expression of Cnr1 and Pomc in the NAcc and TH in the VTA of mice exposed to spontaneous heroin withdrawal. Also, CBD induced an up-regulation of Cnr2, whereas it did not change the increased gene expression of Oprm1 in the NAcc of abstinent animals. The results suggest that CBD alleviates spontaneous heroin withdrawal and normalizes the associated gene expression changes. Future studies are needed to determine the relevance of CBD as a potential therapeutic tool for the treatment of heroin withdrawal. [ABSTRACT FROM AUTHOR]