Addiction treatment

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with diverse psychopharmacological effects including antidepressant and anxiolytic actions. However, the clinical use of BDNF is limited due to its poor pharmacokinetic properties. The development of low-molecular-weight BDNF mimetics passing through the blood-brain barrier is an emerging strategy for improved managing psychiatric diseases. The present study characterizes a novel dipeptide mimetic of the 2nd BDNF loop named GTS-201, which exhibits psychotropic properties in experimental animal models of anxiety and alcohol dependence...

Recent insights into the pathophysiologic underlying mechanisms of obesity have led to the discovery of several promising drug targets and novel therapeutic strategies to address the global obesity epidemic and its comorbidities. Current pharmacologic options for obesity management are largely limited in number and of modest efficacy/safety profile. Therefore, the need for safe and more efficacious new agents is urgent. Drugs that are currently under investigation modulate targets across a broad range of systems and tissues, including the central nervous system, gastrointestinal hormones, adipose tissue, kidney, liver, and skeletal muscle...

Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry...

OBJECTIVE: To determine if adjunctive treatment with a standardized extract of Withania somnifera (WSE), with known anti-inflammatory and immunomodulating properties, improves psychopathology and stress in patients with schizophrenia or schizoaffective disorder (DSM-IV-TR). METHODS: Patients experiencing an exacerbation of symptoms were assigned to WSE (1,000 mg/d) or placebo for 12 weeks, added to their antipsychotic medication, in a random-assignment, double-blind, placebo-controlled study conducted from April 2013 to July 2016...

When facing a choice, most animals quit drugs in favour of a variety of nondrug alternatives. We recently found, rather unexpectedly, that choice of the nondrug alternative is in fact inflexible and habitual. One possible contributing factor to habitual choice is the intermittency and uncontrollability of choice trials in previous studies. Here, we asked whether and to what extent volitional control over the occurrence of choice trials could change animals' preference by preventing habitual choice. To do so, rats were trained to nosepoke in a hole to trigger the presentation of two operant levers: one associated with cocaine, the other with saccharin...

The functional connectivity within and between networks could provide a framework to characterize the neurobiological mechanism of nicotine addiction. This study examined the brain regions that were functionally connected in response to smoking cues and established the brain-behaviour relationships in smokers. Sixty-seven male smokers were enrolled and scanned while performing the cue-reactivity and Stroop task. A whole-brain analysis approach, connectome-based predictive modelling (CPM), was conducted on the data from the cue-reactivity task to identify the networks that could predict the smoking severity with the Shen atlas as templates...

Opioid analgesics exert their therapeutic and adverse effects by activating mu opioid receptors (MOPR), however functional responses to MOPR activation are modulated by distinct signal transduction complexes within the brain. The ventrolateral periaqueductal gray (vlPAG) plays a critical role in modulation of nociception and analgesia, but the exact intracellular pathways associated with opioid responses in this region are not fully understood. We previously showed that knockout of the signal transduction modulator RGSz1 (RGSZ1KO) enhanced analgesic responses to opioids, while it decreased the rewarding efficacy of morphine...

BACKGROUND: The increase in the medical use of cannabis has revealed a number of beneficial effects, a variety of adverse side effects and great inter-individual variability. Association studies connecting consumption, addiction and side effects related to recreational cannabis use have led to the identification of several polymorphic genes that may play a role in the pharmacodynamics and pharmacokinetics of cannabis. METHOD: In total, 600 patients treated with cannabis were genotyped for several candidate polymorphic genes (single-nucleotide polymorphism; SNP), encoding receptors CNR1 and TRPV1; for the ABCB1 transporter; for biotransformation, bioactivation and biosynthesis; and CYP3A4, COMT and UGT2B7 conjugation...

BACKGROUND AND AIMS: Nonsuicidal self-injury (NSSI) is highly prevalent in adolescents and is associated with various mental health problems. Repetitive NSSI (R-NSSI), as an extreme manifestation of NSSI, is a growing concern and has been proposed as a behavioral addiction. However, little is known about the potential addictive mechanisms of NSSI. This study aimed to examine the mediating effect of emotion dysregulation and the moderating effect of impulsivity using the Interaction of Person-Affect-Cognition-Execution (I-PACE) model in adolescents who repeatedly engage in NSSI...

Buprenorphine is a partial mu opioid agonist that has been increasingly utilized to treat patients with chronic pain and opioid use disorder (OUD). The drug has proven to provide significant chronic pain relief at low doses ranging from 75 to 1800 mcg. The conventional buprenorphine transitional process delays its introduction until patients begin withdrawal. However, this process can pose a barrier to both patients and providers due to some patients' inability to tolerate traditional prerequisite withdrawal...

Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents...

BACKGROUND: The generation of the active form of vitamin B-6, pyridoxal 5'-phosphate (PLP), in tissues is dependent upon riboflavin as flavin mononucleotide, but whether this interaction is important for maintaining vitamin B-6 status is unclear. OBJECTIVE: To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. METHODS: Data from 5612 adults aged 18-102 y were drawn from the Irish National Adult Nutrition Survey (NANS; population-based sample) and the Trinity-Ulster Department of Agriculture (TUDA) and Genovit cohorts (volunteer samples)...

OBJECTIVES: To learn how preferences and practices regarding telehealth have evolved during the COVID-19 pandemic for physicians who provide opioid use disorder (OUD) treatment. STUDY DESIGN: Publicly registered physicians who provide OUD treatment were surveyed on their current and retrospective use of telehealth and how their perception of telehealth effectiveness and policy preferences have changed during the COVID-19 pandemic as telehealth regulations were loosened throughout the country...

In the last few years, there has been a wave of articles related to behavioral addictions; some of them have a focus on online pornography addiction. However, despite all efforts, we are still unable to profile when engaging in this behavior becomes pathological. Common problems include: sample bias, the search for diagnostic instrumentals, opposing approximations to the matter, and the fact that this entity may be encompassed inside a greater pathology (i.e., sex addiction) that may present itself with very diverse symptomatology...

BACKGROUND: Novel buprenorphine dosing strategies have emerged with an aim to transition patients from opioid agonists to buprenorphine without prerequisite opioid withdrawal. We applied a configurational approach to a subset of data from our earlier systematic review to answer the following question: when patients received a buprenorphine initiation strategy aimed to eliminate prerequisite withdrawal, what factors consistently distinguished patients that experienced withdrawal during the initiation process from patients that did not? METHODS: From the 24 cases identified by our systematic review, we included cases that were treated using buprenorphine microdosing strategies (oral or transdermal), cases with opioid use disorder, and cases that fully transitioned to buprenorphine without continuing the full opioid agonist...

Pain is a worldwide public health problem and its treatment is still a challenge since clinically available drugs do not completely reverse chronic painful states or induce undesirable effects. Crotalphine is a 14 amino acids synthetic peptide that induces a potent and long-lasting analgesic effect on acute and chronic pain models, peripherally mediated by the endogenous release of dynorphin A and the desensitization of the transient receptor potential ankyrin 1 (TRPA1) receptor. However, the effects of crotalphine on the central nervous system (CNS) and the signaling pathway have not been investigated...

Mitochondrial DNA (mtDNA) mutations are among the most common genetic events in all tumors and directly impact metabolic homeostasis. Despite the central role mitochondria play in energy metabolism and cellular physiology, the role of mutations in the mitochondrial genomes of tumors has been contentious. Until recently, genomic and functional studies of mtDNA variants were impeded by a lack of adequate tumor mtDNA sequencing data and available methods for mitochondrial genome engineering. These barriers and a conceptual fog surrounding the functional impact of mtDNA mutations in tumors have begun to lift, revealing a path to understanding the role of this essential metabolic genome in cancer initiation and progression...

Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and we highlight the general principles of metastasis that have begun to emerge...

OBJECTIVE: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active comparator) plus placebo nasal spray. METHODS: This was a phase 3, double-blind, active-controlled, multicenter study conducted at 39 outpatient referral centers...

Increasing evidence supports a rapid antidepressant and antisuicidal effect of a single subanesthetic dose of ketamine infusion for treatment-resistant depression (TRD). Maintaining the initial clinical response after ketamine infusion in TRD is a crucial next-step challenge. D-cycloserine (DCS), a partial agonist of the glycine co-agonist of the N-methyl-D-aspartate (NMDA) glutamate receptor, is potentially effective as a depression augmentation treatment. However, whether DCS maintains the antidepressant and antisuicidal effects of ketamine infusion remains unknown...