Blum Kenneth, Mohankumar Kavya, Bagchi Debasis, Lewandrowski Kai Uwe, Sharafshah Alireza, Elman Igor, Gold Mark S, Dennen Catherine A, Thanos Panayotis K, Pinhasov Albert, Bowirrat Abdalla, Lewandrowski Alexander Pl, Baron David, Modestino Edward J, Fuehrlein Brian, Khalsa Jag, Gastelu Daniel, Fliegelman Chynna, Sunder Keerthy, Murphy Kevin T, Makale Milan, Madigan Margaret A, Lindenau Marco, Swaroop Anand, Badgaiyan Rajendra D
Center for Exercise and Sport Mental Health, Western University Health Sciences, Pomona, USA.
Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel.
Neurology (ECronicon). 2025 Jul;17(7). Epub 2025 Jun 13.
Dopaminergic dysfunction in reward circuitry is well-documented as a contributor to addictive behaviors. Evidence indicates that changes in synchronous neural activity between brain regions mediating reward and cognitive functions may significantly contribute to substance-related disorders. In this commentary we highlight findings showing that the pro-dopaminergic nutraceutical (KB220) enhances functional connectivity between reward and cognitive brain areas in both animal and human studies. Animal studies demonstrate that KB220 activates important brain reward-related regions, including the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, and prelimbic and infralimbic loci. Kb220 induced significant functional connectivity, enhanced neuroplasticity, and improved dopaminergic functionality within the brain reward circuitry with effects localized to these regions rather than broader distributed across the brain. In abstinent heroin-dependent individuals, acute KB220 administration significantly induced BOLD activation in caudate-accumbens dopaminergic pathways relative to placebo. Furthermore, data from 36 clinical trials and preclinical studies encompassing over 1,000 subjects, demonstrate that KB220 supports "dopamine homeostasis" across various reward deficiency behaviors. Clinical outcomes and quantitative electroencephalogy (qEEG) results underscore KB220's potential anti-craving/anti-relapse effects in addiction and other psychiatric disorders through direct or indirect dopaminergic modulation. Based on a review of the existing knowledge and further intensive investigation, we propose that instead of relying on mono-pharmaceutical approaches, the scientific community should endorse multi-loci dopaminergic restoration of reward brain circuitry as a fundamental paradigm for addressing mental illness.
奖赏回路中的多巴胺能功能障碍是成瘾行为的一个重要促成因素，这一点已有充分记录。有证据表明，介导奖赏和认知功能的脑区之间同步神经活动的变化可能在物质相关障碍中起重要作用。在这篇评论中，我们强调了一些研究结果，这些结果表明，在动物和人类研究中，促多巴胺能营养保健品（KB220）增强了奖赏脑区和认知脑区之间的功能连接。动物研究表明，KB220激活了重要的脑奖赏相关区域，包括伏隔核、前扣带回、丘脑前核、海马以及前额叶和边缘下叶位点。KB220在脑奖赏回路中诱导了显著的功能连接，增强了神经可塑性，并改善了多巴胺能功能，其作用局限于这些区域，而非广泛分布于整个大脑。在戒除海洛因依赖的个体中，相对于安慰剂，急性给予KB220显著诱导了尾状核-伏隔核多巴胺能通路的血氧水平依赖（BOLD）激活。此外，来自36项临床试验和临床前研究、涵盖1000多名受试者的数据表明，KB220在各种奖赏缺乏行为中支持“多巴胺稳态”。临床结果和定量脑电图（qEEG）结果强调了KB220通过直接或间接的多巴胺能调节，在成瘾和其他精神疾病中潜在的抗渴望/抗复发作用。基于对现有知识的回顾和进一步深入研究，我们建议，科学界不应依赖单一药物治疗方法，而应支持多靶点多巴胺能恢复奖赏脑回路，将其作为解决精神疾病的基本范式。
