Effective therapy of insomnia, especially chronic insomnia, is one of the most pressing neuropsychiatric problems. Unfortunately, at present in the Russian Federation, as in most other countries of the world, there are no officially approved drugs for long-term treatment of insomnia. In this regard, the use of medical sedation agents that do not have restrictions on the duration of use is of considerable interest. This review considers drugs of various psychopharmacological classes, one way or another used in practice for the correction of sleep disorders, especially in patients with underlying comorbid pathology.

Изучение нейробиологических основ систем положительного и отрицательного подкрепления имеет огромное значение для разработки методов фармакотерапии зависимости от психоактивных веществ (ПАВ). В течение многих лет при исследовании мотивационных составляющих аддиктивного влечения основное внимание уделялось положительно-подкрепляющим свойствам ПАВ. Вместе с тем феномен «отрицательного подкрепления», ассоциированный с негативным эмоциональным состоянием, играет ключевую роль при формировании аддиктивного поведения. Одним из основных «субстратов» этого состояния считают динорфин/каппа-опиоидную систему мозга. В данной обзорной статье мы ограничились рассмотрением роли этой системы в реализации эффектов алкоголя и попытались представить сложную картину взаимодействия динорфин/каппа-опиоидной с дофаминовой и другими нейромедиаторными системами и ее роль на различных этапах формирования алкогольной...

Relevance . In modern society, the spectrum of cardiac surgical pathology that develops in chronic drug users has expanded significantly and is not limited only to infectious lesions of the heart valves. This dictates the need for an in-depth study of the pathophysiological mechanisms of the effects of various narcotic substances on cardiac structures in order to develop a differentiated approach to the treatment of these patients. The literature review concerns the need of development of approach to the treatment of cardiac surgical patients with comorbid past or current drug abuse, depending on the type of narcotic substance used. Conclusion . The development of a differentiated approach that considers the mechanisms of cardiovascular toxicity of various narcotic substances might help elaborate the ways to reduce the pathological changes yielding in significant improvement in treatment of these patients.

Recent Phase 3 clinical trials of selective kappa-opioid peptide (KOP) receptor antagonists – aticaprant (Johnson & Johnson, VENTURA trial, 2025) and navacaprant (Neumora, KOASTAL-1 trial, 2025) – failed to demonstrate sufficient clinical efficacy in treatment-resistant depression (TRD). We propose two hypotheses that could explain these setbacks: (1) neutral antagonists may be poorly effective in patients with TRD due to constitutive KOP receptor hyperactivation and (2) the KOP receptor paralog – nociceptin opioid peptide (NOP) receptor – can effectively compensate for KOP receptor blockade decreasing the magnitude of clinical efficacy. We hypothesize that functional redundancy provided by NOP receptor signaling requires dual KOP/NOP blockade to achieve clinically meaningful improvement in reward function. Recent insights gained from paralogous compensation in drug-resistant tumors underscore the need for dual-target approaches. We propose that future studies, if successful, may yield a novel pharmacological class targeting opioid-mediated hedonic suppression, advocating for the development of opioid inverse agonists (such as norBNI), pan-antagonists (such as AT-076), and combinations of selective blockers.

Gambling disorder (GD) is a behavioral addiction characterized by high comorbidity, significant social and economic consequences. The neurobiological mechanisms underlying GD are similar to those observed in substance use disorders, which opens possibilities for pharmacological intervention. However, no medication has yet been approved for the treatment of GD, and the evidence base for existing agents remains limited. This review summarizes data on the pharmacological treatment of GD based on current systematic reviews and network meta-analyses, and discusses methodological limitations and clinical prospects for the use of various drug classes. This narrative literature review was conducted, encompassing clinical trials, case series, and open-label studies of opioid antagonists, antipsychotics, mood stabilizers, anticonvulsants, antidepressants, gabapentinoids, and other agents. The most compelling evidence was found for nalmefene and naltrexone, which produced statistically significant reductions in GD symptoms compared to placebo, particularly in patients with high craving. Antidepressants, olanzapine, and topiramate failed to outperform placebo in most studies. Mood stabilizers may be beneficial in cases of comorbid bipolar disorder, but the evidence remains very limited. N-acetylcysteine, memantine and gabapentinoids showed encouraging preliminary results; GLP-1 receptor agonists, ketamine, and psilocybin remain experimental. Thus, opioid antagonists may be considered a first-line (off-label) therapy for GD, complementing rather than replacing cognitive-behavioral therapy. Larger controlled trials and the identification of biomarkers for treatment personalization are needed.