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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 Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the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.

BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. METHODS: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. RESULTS: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. CONCLUSIONS: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients withdrawal experiences.

Cigarette smoking remains a leading cause of preventable disease and death worldwide. Due to the devastating negative health effects of smoking, many users attempt to quit, but few are successful in the long-term. Thus, there is a critical need for novel therapeutic approaches. In these investigations, we sought to examine whether cannabidiol (CBD) has the potential to be repurposed as a nicotine cessation therapeutic. In the first study, male and female mice were trained to respond for intravenous nicotine infusions at either a low or moderate nicotine dose and then were pretreated with CBD prior to their drug-taking session. We found that CBD produced a significant decrease in the number of nicotine rewards earned, and this effect was evidenced across CBD doses and with both the low and moderate levels of nicotine intake. These effects on drug intake were not due to general motor-related effects, since mice self-administering food pellets did not alter their behavior with CBD administration. The potential effects of CBD in mitigating nicotine withdrawal symptoms were then investigated. We found that CBD attenuated the somatic signs of nicotine withdrawal and prevented nicotine's hyperalgesia-inducing effects. Taken together, these results demonstrate that modulation of cannabinoid signaling may be a viable therapeutic option as a smoking cessation aid.

Introduction: Despite recommendations for ambulatory withdrawal programs appearing in many contemporary alcohol and other drug treatment guidelines, to date there have been few studies exploring such programs from client and service stakeholder perspectives. The aim of this study was to explore both individual and service stakeholder perceptions of a nurse practitioner‐led ambulatory withdrawal service on the Gold Coast, Queensland, Australia. Methods: Data were obtained from three groups: clinicians with knowledge of the service (n = 6); relatives of clients who had used the service (n = 2); and clients who had used the service (n = 10) using a Qualitative Descriptive design. Saldaña's (Saldaña, The coding manual for qualitative researchers. 2013) structural coding framework was used to analyse and code data into themes, with the study reported in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist (Tong et al. Int J Qual Health Care 2017;19:349–57). Results: Participants noted advantages of the nurse practitioner‐led ambulatory withdrawal service, including rapid availability of admission to the service and a person‐centred approach. Compared with other ambulatory withdrawal options, clients valued the ability to remain in their own environment, however participants suggested greater follow‐up after withdrawal, with the potential of a home visiting service for greater client engagement and treatment retention. Discussion and Conclusions: Findings provide evidence to suggest that nurse practitioner‐led ambulatory withdrawal services are an acceptable option for a proportion of clients who need rapid access to services when they wish to make changes to their alcohol and/or other drug use. Furthermore, they can provide person‐centred care for comorbid physical and mental ill health occurring in addition to psychosocial issues associated with alcohol and/or other drug use. [ABSTRACT FROM AUTHOR]

Background The physical dependence on prescription opioids among cancer survivors remains an under-investigated area, with a scarcity of well-designed prospective studies. Methods This single-arm, phase-2 clinical trial in Korea assessed the efficacy and safety of a transdermal buprenorphine patch (TBP) in managing physical dependence on prescription opioids in cancer survivors, as confirmed through the DSM-5 criteria or psychiatric consultation for opioid withdrawal. This study involved a 4-phase treatment protocol of screening, induction/stabilization, discontinuation, and monitoring. The primary outcome was the rate of successful opioid discontinuation, as measured by a negative urine-drug screening at 8 weeks. Key secondary outcomes included the resumption of prescribed opioids, changes in both the Clinical Opioid Withdrawal Scale (COWS) and morphine equivalent daily dose (MEDD), and assessments related to the psychological and physiological aspects of dependence and safety. Results Thirty-one participants were enrolled. In the intention-to-treat population, the success rate of opioid discontinuation was 58%, with only 2 participants experiencing a resumption of prescribed opioids. Significant reductions were observed in MEDD, which decreased from 98 to 26 mg/day (P  < .001), and COWS scores, which decreased from 5.5 to 2.8 (P  < .001). Desire to use opioids reduced from 7.0 to 3.0 on a 10-point numeric rating scale (P  < .001). Toxicities related to TBP were mild and manageable, without severe precipitated withdrawal symptoms. Conclusion TBP may be considered as an alternative therapeutic option in cancer survivors physically dependent on prescription opioids, especially where sublingual formulations are unavailable. [ABSTRACT FROM AUTHOR]

Opioids are considered one of the mainstays of pain treatment. However, they are not exempted from potential risks, such as withdrawal caused by their rapid decline or abrupt cessation. It is usual to observe a high number of withdrawal cases in clinical practice, especially in special populations such as children and in critically ill patients. Considering the clinical importance of opioids and the permanent search to minimize secondary events related to their use, this update was carried out to review the existing proposals in the literature and suggest a didactic way to perform opioid tapering in pediatric and neonatal population in intensive care units. As a result, the “DESSMONTE” strategy arises, which is an acrostic in Spanish that allows guidance on the eight essential steps for an organized and predictable weaning protocol in critically ill pediatric patients. The strategy is flexible, which would allow it to be adapted to different clinical scenarios.

Recent controversies have arisen regarding claims of uncritical positive regard and hype surrounding psychedelic drugs and their therapeutic potential. Criticisms have included that study designs and reporting styles bias positive over negative outcomes. The present study was motivated by a desire to address this alleged bias by intentionally focusing exclusively on negative outcomes, defined as self-perceived negative psychological responses lasting for at least 72 h after psychedelic use. A strong justification for this selective focus was that it might improve our ability to capture otherwise missed cases of negative response, enabling us to validate their existence and better examine their nature, as well as possible causes, which could inspire risk-mitigation strategies. Via advertisements posted on social media, individuals were recruited who reported experiencing negative psychological responses to psychedelics (defined as classic psychedelics plus MDMA) lasting for greater than 72 h since using. Volunteers were directed to an online questionnaire requiring quantitative and qualitative input. A key second phase of this study involved reviewing all of the submitted cases, identifying the most severe-e.g., where new psychiatric diagnoses were made or pre-existing symptoms made worse post psychedelic-use-and inviting these individuals to participate in a semi-structured interview with two members of our research team, during which participant experiences and backgrounds were examined in greater depth. Based on the content of these interviews, a brief summary of each case was compiled, and an explorative thematic analysis was used to identify salient and consistent themes and infer common causes. 32 individuals fully completed an onboarding questionnaire (56% male, 53%

Background & Objectives: Drug addiction constitutes a global issue associated with severe personal, economic, social, and health problems. Saffron, an herbal medicine, has demonstrated potential therapeutic applications for mental and physical symptoms. This review assesses the efficacy of saffron crocin in managing the clinical and psychological complications of opioid substance withdrawal syndrome(OWS). Materials & Methods: The research methodology entailed a comprehensive literature review spanning from 2010 to 2023, utilizing databases such as Scopus, PubMed, Embase, and Web of Science. The search focused on the impact of saffron crocin on clinical and psychological complications of OWS. Human randomized controlled trials (RCTs) and animal studies published in English were included for data synthesis. Subsequently, information was collated based on the following parameters: study author, number of studies, dosage, control group, duration, outcome criteria, and primary outcomes. Results: Eight articles were analyzed, demonstrating the efficacy of saffron and crocin in treating OWS by ameliorating withdrawal symptoms and improving laboratory indicators. Conclusion: While several RCTs support the effectiveness of saffron crocin in alleviating OWS symptoms, further rigorous studies are warranted to corroborate these findings. [ABSTRACT FROM AUTHOR]

Objectives: Treating acute opioid withdrawal and offering medications for opioid use disorder (OUD) is critical. Hospitalization offers a unique opportunity to rapidly initiate methadone for OUD; however, little clinical guidance exists. This report describes our experience during the first 9 months following introduction of a hospital-based rapid methadone initiation protocol. Methods: We conducted a retrospective chart review of hospitalized patients with OUD seen by our interprofessional addiction medicine consult service at an urban academic center between December 2022 and August 2023.We identified patients who initiated methadone using the rapid methadone initiation protocol, which includes dose recommendations (maximum 60 mg day 1, 70 mg day 2, 80 mg day 3, 100 mg days 4–7) and strict inclusion and exclusion criteria (end organ failure, arrhythmia, concurrent benzodiazepine or alcohol use, age >65). Results: There were 171 patients that received methadone for OUD during the study period. Of those, 25 patients (15%) received rapid methadone initiation. The average total daily dose of methadone on days 1–7 was 53.0 mg, 69.2 mg, 75.4 mg, 79.5 mg, 87.1 mg, 92.2 mg, and 96.6 mg, respectively. There were no adverse events requiring holding a dose of scheduled methadone, naloxone administration, or transfer to higher level of care. Conclusions: A rapid methadone initiation protocol for OUD can be implemented in the inpatient setting. Patients up-titrated their methadone doses quicker than with traditional induction methods, and there were no serious adverse events. Appropriate patient selection may be important to avoid harms. [ABSTRACT FROM AUTHOR]

AbstractAn increasing number of new psychoactive substances (NPS), such as designer benzodiazepines, are becoming available on the recreational drug market. These are new unregistered substances and thereby an attempt to evade legislation. Often there is very limited clinical information available regarding these NPS, which could result in undesirable clinical outcomes in the management of intoxications, dependencies and withdrawals following NPS use. In this case report we describe a 23-year-old woman, who was admitted to our residential addiction care facility for the detoxification of the designer benzodiazepine bromazolam. Her daily use of 6 mg bromazolam was converted to 20 mg diazepam. Although we expected a higher dose would have been needed, 20 mg was sufficient and was tapered without complications. This case report demonstrates the safe conversion of 6 mg of bromazolam to 20 mg of diazepam by combining the use of fixed-dose and symptom-triggered-dose regimens. More clinical data is necessary to formulate advisory management for the detoxification of bromazolam and other designer benzodiazepines. [ABSTRACT FROM AUTHOR]

Chronic nicotine results in dependence with withdrawal symptoms on discontinuation of use, through desensitization of nicotinic acetylcholine receptors and altered cholinergic neurotransmission. Nicotine withdrawal is associated with increased whole-brain functional connectivity and decreased network modularity; however, the role of cholinergic neurons in those changes is unknown. To identify the contribution of nicotinic receptors and cholinergic regions to changes in the functional network, we analyzed the contribution of the main cholinergic regions to brain-wide activation of the immediate early-gene Fos during withdrawal in male mice and correlated these changes with the expression of nicotinic receptor mRNA throughout the brain. We show that the main functional connectivity modules included the main long-range cholinergic regions, which were highly synchronized with the rest of the brain. However, despite this hyperconnectivity, they were organized into two anticorrelated networks that were separated into basal forebrain-projecting and brainstem-thalamic-projecting cholinergic regions, validating a long-standing hypothesis of the organization of the brain cholinergic systems. Moreover, baseline (without nicotine) expression of Chrna2, Chrna3, Chrna10, and Chrnd mRNA of each brain region correlated with withdrawal-induced changes in Fos expression. Finally, by mining the Allen Brain mRNA expression database, we were able to identify 1755 gene candidates and three pathways (Sox2-Oct4-Nanog, JAK-STAT, and MeCP2-GABA) that may contribute to nicotine withdrawal-induced Fos expression. These results identify the dual contribution of the basal forebrain and brainstem-thalamic cholinergic systems to whole-brain functional connectivity during withdrawal; and identify nicotinic receptors and novel cellular pathways that may be critical for the transition to nicotine dependence.