Pharmacological management of gambling disorder: an update of the literature.

INTRODUCTION: Gambling disorder (GD) is a mental health condition characterized by persistent and problematic betting behavior. GD generates distress and impairment, and treatment options include psychological and pharmacological interventions. AREAS COVERED: This narrative review explores existing pharmacological treatments for GD. The following classes of medications were considered: opioid-receptor antagonists (e.g. naltrexone and nalmefene), serotonin reuptake inhibitors (e.g. fluvoxamine, paroxetine, sertraline, escitalopram, and citalopram), glutamatergic agents (e.g. N-acetylcysteine (NAC), acamprosate, and memantine), mood stabilizers (e.g. topiramate, carbamazepine, lithium), and other medications (e.g. modafinil, nefazodone, olanzapine, haloperidol, tolcapone, and bupropion). EXPERT OPINION: Due to the limitations of the studies reviewed, solid conclusions regarding the optimal choice of pharmacotherapy for individuals with GD are challenging to draw at this time. Despite some medications, such as naltrexone and nalmefene, showing promising results, efficacy has varied across studies. The review highlights current gaps/limitations, including small sample sizes, limited diversity in participant demographics, the need for exploring different gambling subtypes and treatment responses, high placebo response rates, lack of longer-term longitudinal information, limited investigation of neurobiological correlates and co-occurring disorders, and the importance of implementation research. Further research is needed to address these gaps and explore additional medications, as well as interventions like neuromodulation.

Efficacy of Methylphenidate for Internet Gaming Disorder and Internet Addiction in Patients with Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Internet Gaming Disorder (IGD) and Internet Addiction (IA) are related clinical conditions often comorbid with Attention-Deficit/Hyperactivity Disorder (ADHD). OBJECTIVE: We evaluated the efficacy of MPH for IGD/IA symptoms in ADHD patients. METHODS: We enrolled 38 drug-naive patients diagnosed with ADHD (Attention-Deficit/Hyperactivity Disorder) and IGD/IA. At baseline, all patients underwent a clinical assessment for IGD/IA symptoms and then received the most appropriate therapy according to their clinical profile. Twenty-one patients received MPH (methylphenidate) treatment, and 17 patients did not. Patients were re-evaluated after three months of treatment. RESULTS: Findings revealed significant reductions in IGD/IA symptoms over time, while no significant effect of MPH on symptom reduction was found. Clinical predictors of symptom reduction were identified, including IQ (Intelligence Quotient) and comorbid anxiety. CONCLUSION: This longitudinal prospective study contributes to the understanding of IGD/IA treatment in ADHD patients and highlights the importance of considering individual clinical characteristics when predicting treatment response. However, MPH may not directly impact IGD/IA symptom reduction.

Hot weight loss drugs tested against addiction.

Clinical trials will gauge whether GLP-1 analogs curb drug and alcohol cravings.

Addiction specialists' attitudes toward psychedelics: A National Survey.

BACKGROUND AND OBJECTIVES: In recent years, there has been accelerating scientific and public interest in the use of psychedelics to treat mental health disorders. Our study's objective was to assess the attitudes of addiction specialists regarding therapeutic psychedelics. METHODS: Our study utilized an anonymous online survey to assess the opinions of 145 addiction specialists regarding the therapeutic promise, potential risks, and legalization of psychedelics in the treatment of psychiatric illness and substance use disorders. Psychedelics were defined in the survey as inclusive of nonserotonergic hallucinogens such as ketamine or MDMA in addition to "classic" serotonergic psychedelics. RESULTS: Most respondents expressed positive attitudes to the therapeutic use of psychedelics, but a sizeable minority expressed concern for their addictive potential. Familiarity with psychedelic scientific literature was the strongest positive predictor of belief in the therapeutic potential of psychedelics, while concern for addictive potential was the strongest negative predictor. DISCUSSION AND CONCLUSIONS: Participants overall expressed more positive attitudes to the therapeutic use of psychedelics than we had hypothesized. This may be attributable to the accelerating pace of psychedelics research in recent years. Given the strong influence of concern for addiction risk on attitudes, future study is warranted to explore the findings regarding these concerns. These findings may also represent an opportunity for improved education of physicians regarding the addictive potential, and relative risks/benefits of psychedelics. SCIENTIFIC SIGNIFICANCE: Though there have been several prior studies assessing psychiatrist and psychologist attitudes toward psychedelics, we are unaware of any specifically examining the opinions of addiction specialists.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction.

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

Blockade of the Dopamine D3 Receptor Attenuates Opioids-Induced Addictive Behaviours Associated with Inhibiting the Mesolimbic Dopamine System.

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D3 receptor (D3R) have effects on addiction in different animal models. We have previously reported that YQA14, a D3R antagonist, exhibits very high affinity and selectivity for D3Rs over D2Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D3R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.

Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction / 中国结合医学杂志

With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.

The Role of the Cerebellum in Drug Reward: A Review.

Drug abuse remains a global problem; nonetheless, its mechanism has not yet been fully understood. Recent studies have reported on the non-motor functions of the cerebellum, and evidence from neuroimaging and behavioral studies has suggested the role of cerebellum in drug reward, which has received increasing attention. Furthermore, emerging technological developments have aided in clarifying the various circuits and functions of the cerebellum. Exploring the role of the cerebellum in drug reward can improve our understanding of the mechanism underlying addiction and facilitate the development of new treatment schemes. This review summarizes the anatomy of the cerebellum and its connections to brain regions considered important in addiction. Subsequently, we investigate the neurological reasons elucidating why the cerebellum is a potential target for drug reward. Additionally, we expound the molecular targets of addictive drugs in the cerebellum, mainly glutamate and endocannabinoids. Unlike previous studies, this article focuses on the influence of alcohol, nicotine, morphine, cannabis, and cocaine on the cerebellum from multiple viewpoints, including imaging and behavioral changes, molecular signals, neurotransmitters, and synaptic transmission. We aim to clarify some drug-induced cerebellar changes to supplement the previous research regarding the relationship between addiction and the cerebellum. Finally, we discuss the limitations and prospects of drug reward research on the cerebellum to provide novel insights into studying the cerebellum and its role in addiction. We recommend that future addiction network models should include the cerebellum to provide new therapeutic targets for treating addiction.

Usage of L-type calcium channel blockers to suppress drug reward and memory driving addiction: Past, present, and future.

Over the past three decades, L-type Ca2+ channel (LTCC) blockers have been considered a potential therapeutic drug to alleviate the symptoms of drug addiction. This idea has been supported, in part, by 1) expression of LTCCs in the brain dopaminergic circuits that are thought to play critical roles in the development and expression of addictive behaviors and 2) common usage of LTCC blockers in treating hypertension, which may enable off-label use of these drugs with good brain penetration as therapeutics for brain disorders. Addiction can be viewed as a maladaptive form of learning where powerful memories of drug-associated stimuli and actions drive compulsive drug intake. Largely under this framework, we will focus on the dopaminergic system that is thought be critically involved in drug-associated learning and memory and provide a brief overview of the past and recent studies testing the therapeutic potential of LTCC blockers for addictive disorders in animal models and humans and offer a future perspective on the use of LTCC blockers in drug addiction and, possibly, addiction to other non-drug rewards (e.g., gambling, eating, shopping). Interested readers can refer to other related articles in this issue and a comprehensive review available elsewhere (Little, 2021) to gain further insights into the roles of LTCCs in drug addiction and withdrawal symptoms associated with dependence. This article is part of the Special Issue on 'L-type calcium channel mechanisms in neuropsychiatric disorders'.

Why haven't we solved the addiction crisis?

The current addiction crisis has destroyed a multitude of lives, leaving millions of fatalities worldwide in its wake. At the same time, various governmental agencies dedicated to solving this seemingly never-ending dilemma have not yet succeeded or delivered on their promises. We understand that addictive behavioral seeking is a multi-faceted neurobiological and spiritually complicated phenomenon. However, although the substitution replacement approach, especially to treat Opioid Use Disorder (OUD), has importance for harm reduction in the short term, it does not bring about a harm-free recovery or prevention. Instead, we propose a promising novel approach that uses genetic risk testing with induction of dopamine homeostasis and an objective Brain Health Check during youth. Our model involves a six-hit approach known as the "Reward Dysregulation Syndrome Solution System," which can identify addiction risk and target the root cause of addiction, dopamine dysregulation. While we applaud all past sophisticated neurogenetic and neuropharmacological research, our opinion is that in the long term, addiction scientists and clinicians might characterize preaddiction using tests; for example, administering the validated RDSQuestionarre29, genetic risk assessment, a modified brain health check, or diagnostic framing of mild to moderate Substance Use Disorder (SUD). The preaddiction concept could incentivize the development of interventions to prevent addiction from developing in the first place and target and treat neurotransmitter imbalances and other early indications of addiction. WC 222.

Substance abuse and neurotransmission.

The number of people who suffer from a substance abuse disorder has continued to rise over the last decade; particularly, the number of drug-related overdose deaths has sharply increased during the COVID-19 pandemic. Converging lines of clinical observations, supported by imaging and neuropsychological performance testing, have demonstrated that substance abuse-induced dysregulation of neurotransmissions in the brain is critical for development and expression of the addictive properties of abused substances. Recent scientific advances have allowed for better understanding of the neurobiological processes that mediates drugs of abuse and addiction. This chapter presents the past classic concepts and the recent advances in our knowledge about how cocaine, amphetamines, opioids, alcohol, and nicotine alter multiple neurotransmitter systems, which contribute to the behaviors associated with each drug. Additionally, we discuss the interactive effects of HIV-1 or COVID-19 and substance abuse on neurotransmission and neurobiological pathways. Finally, we introduce therapeutic strategies for development of pharmacotherapies for substance abuse disorders.

Perspective: Can psychedelic-assisted therapy be a promising aid in compulsive sexual behavior disorder treatment?

Recently, there has been an increase in studies yielding evidence for psychedelics' anxiolytic and anti-depressive qualities. Preliminary evidence for treatment in substance addiction is also available. In our manuscript, we present a perspective on the possible effectiveness and mechanisms of action of psychedelics' introduction in the treatment of Compulsive Sexual Behavior Disorder (CSBD) and other p roblematic sexual behaviors, which are considered representative of the so-called "behavioral addiction" category. Evidence for the efficacy of Mindfulness Based Interventions in CSBD treatment is promising. Psychedelics- and mindfulness-induced states share common characteristics on both a subjective and objective level. One of the proposed mechanisms regards reduction of experiential avoidance through the promotion of exposure and acceptance. On the neurophysiological level, a shift from higher- to lower-level association regions and an impact on 5- HT2A receptors is observed. Elaborated mechanisms explain the possible enhancement of therapeutic processes by psychedelics. Psychedelics' relative safety and low addictive potential support their introduction into traditional forms of therapy for CSBD and other out of control behaviors.

Support Models for Addiction Related Treatment (SMART) for pregnant women: Study protocol of a cluster randomized trial of two treatment models for opioid use disorder in prenatal clinics.

INTRODUCTION: The prevalence of opioid use disorder (OUD) in pregnancy increased nearly five-fold over the past decade. Despite this, obstetric providers are less likely to treat pregnant women with medication for OUD than non-obstetric providers (75% vs 91%). A major reason is many obstetricians feel unprepared to prescribe medication for opioid use disorder (MOUD). Education and support may increase prescribing and overall comfort in delivering care for pregnant women with OUD, but optimal models of education and support are yet to be determined. METHODS AND ANALYSIS: We describe the rationale and conduct of a matched-pair cluster randomized clinical trial to compare the effectiveness of two models of support for reproductive health clinicians to provide care for pregnant and postpartum women with OUD. The primary outcomes of this trial are patient treatment engagement and retention in OUD treatment. This study compares two support models: 1) a collaborative care approach, based upon the Massachusetts Office-Based-Opioid Treatment Model, that provides practice-level training and support to providers and patients through the use of care managers, versus 2) a telesupport approach based on the Project Extension for Community Healthcare Outcomes, a remote education model that provides mentorship, guided practice, and participation in a learning community, via video conferencing. DISCUSSION: This clustered randomized clinical trial aims to test the effectiveness of two approaches to support practitioners who care for pregnant women with an OUD. The results of this trial will help determine the best model to improve the capacity of obstetrical providers to deliver treatment for OUD in prenatal clinics. TRIAL REGISTRATION: Clinicaltrials.gov trial registration number: NCT0424039.

Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors.

In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain". Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics.

CB1 receptor antagonist AM4113 reverts the effects of cannabidiol on cue and stress-induced reinstatement of cocaine-seeking behaviour in mice.

No pharmacological treatments are yet approved for patients with cocaine use disorders. Cannabidiol, a constituent of the C. sativa plant has shown promising results in rodent models of drug addiction. However, the specific effects and mechanisms of action of cannabidiol in rodent operant models of extinction-based abstinence and drug-seeking relapse remain unclear. Cannabidiol (10 and 20 mg/kg, i.p.) was injected during extinction training to male CD-1 mice previously trained to self-administer cocaine (0.75 mg/kg/infusion). Then, we evaluated the reinstatement of cocaine seeking induced by cues and stressful stimuli (footshock). We found that cannabidiol (10 and 20 mg/kg) did not modulate extinction learning. After cannabidiol 20 mg/kg treatment, increased levels of CB1 receptor protein were found in the prelimbic and orbitofrontal regions of the prefrontal cortex, and in the ventral striatum; an effect paralleled by a reduction of striatal ∆FosB accumulation and an increment of GluR2 AMPA receptor subunits. Furthermore, cue-induced reinstatement of cocaine seeking was attenuated by cannabidiol. Unexpectedly, cannabidiol 20 mg/kg facilitated stress-induced restoration of cocaine-seeking behaviour. To ascertain the participation of CB1 receptors in these behavioural changes, we administered the CB1 antagonist AM4113 (5 mg/kg) before each reinstatement session. Both, the attenuation of cue-induced reinstatement and the facilitation of stress-induced reestablishment were abolished by AM4113 in cannabidiol 20 mg/kg-treated mice. Our results reveal a series of complex CB1-related changes induced by cannabidiol with a varying impact on the reinstatement of cocaine-seeking behaviour that could limit its therapeutic applications.

Ameliorative effects of alkaloid extract from Mitragyna speciosa (Korth.) Havil. Leaves on methamphetamine conditioned place preference in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) Havil., popularly known as Kratom (KT), is a medicinal plant used for pain suppression in Southeast Asia. It has been claimed to assist drug users withdraw from methamphetamine (METH) dependence. However, its use was controversial and not approved yet. AIM OF THE STUDY: This study was conducted to characterize local field potential (LFP) patterns in the nucleus accumbens (NAc) and the hippocampus (HP) in mice with METH conditioned place preference (CPP) that were treated with KT alkaloid extract. MATERIALS AND METHODS: Male Swiss albino ICR mice were implanted with intracraneal electrodes into the NAc and HP. To induce METH CPP, animals were injected intraperitoneally once a day with METH (1 mg/kg) and saline (0.9% w/v) alternately and put into METH/saline compartments to experience the associations between drug/saline injection and the unique environmental contexts for 10 sessions. Control group received saline injection paired with both saline/saline compartments. On post-conditioning day, effects of 40 (KT40), 80 (KT80) mg/kg KT alkaloid extract and 20 mg/kg bupropion (BP) on CPP scores and LFP powers and NAc-HP coherence were tested. RESULTS: Two-way ANOVA revealed significant induction of CPP by METH sessions (P < 0.01). Multiple comparisons indicated that METH CPP was completely abolished by KT80 (P < 0.001). NAc gamma I (30.0-44.9 Hz) and HP delta (1.0-3.9 Hz) powers were significantly increased in mice with METH CPP (P < 0.01). The elevated NAc gamma I was significantly suppressed by KT80 (P < 0.05) and the increased HP delta was significantly reversed by KT40 (P < 0.01) and KT80 (P < 0.001). In addition, NAc-HP coherence was also significantly increased in gamma I (30.0-44.9 Hz) frequency range (P < 0.05) but it was reversed by KT80 (P < 0.05). Treatment with BP did not produce significant effect on these parameters. CONCLUSIONS: These findings demonstrated that KT alkaloid extract significantly reversed CPP scores and LFP patterns induced by METH administration. The ameliorative effects of the extract might be beneficial for treatment of METH craving and addiction.

New Insights in the Involvement of the Endocannabinoid System and Natural Cannabinoids in Nicotine Dependence.

Nicotine, the main psychoactive component in tobacco smoke, plays a major role in tobacco addiction, producing a high morbidity and mortality in the world. A great amount of research has been developed to elucidate the neural pathways and neurotransmitter systems involved in such a complex addictive behavior. The endocannabinoid system, which has been reported to participate in the addictive properties of most of the prototypical drugs of abuse, is also implicated in nicotine dependence. This review summarizes and updates the main behavioral and biochemical data involving the endocannabinoid system in the rewarding properties of nicotine as well as in nicotine withdrawal and relapse to nicotine-seeking behavior. Promising results from preclinical studies suggest that manipulation of the endocannabinoid system could be a potential therapeutic strategy for treating nicotine addiction.

Can intranasal oxytocin reduce craving in automated addictive behaviours? A systematic review.

Existing pharmacotherapies for managing craving, a strong predictor of relapse to automated addictive behaviours, are limited in efficacy and characterised by increased health risks associated with their pharmacological profile. Preclinical studies have identified oxytocin as a promising pharmacotherapy with anticraving properties for addictive behaviours. Here, we provide the first systematic review of 17 human studies (n = 722; 30% female) investigating the efficacy of intranasal oxytocin to reduce craving or consumption in addictive behaviours. We identify intranasal oxytocin as a method that warrants further investigation regarding its capacity to decrease cue-induced, acute stress-induced or withdrawal-related craving and relapse related to alcohol, cannabis, opioids, cocaine or nicotine, including a potential role as ad hoc medication following exposure to drug-related cues. Future studies should investigate the role of factors such as treatment regimens and sample characteristics, including the role of the amygdala, which we propose as a distinct mechanism mediating oxytocin's anticraving properties.