This article discusses the role of brain neurotrophic factors (NTFs) in the development of the syndrome of psychological addiction to psychoactive substances. The data on the impairments of NTF metabolism after acute and chronic drug action are summarized. The changes in the addictive activity of psychoactive substances were analyzed in rodents with defective genes for neurotrophic factors and under conditions of modified metabolism of the examined regulatory proteins. We concluded that the brain-derived neurotrophic factor may enhance the addictive potential of cocaine. The glial neurotrophic factor and tumor necrosis factor-α show anti-addictive activities during consumption of cocaine, methamphetamine, morphine, and ethanol. The brain-derived neurotrophic factor inhibits the development of psychological addiction to ethanol. The leucine-isoleucine dipeptide increases the concentration of glial neurotrophic factor and tumor necrosis factor-α in the mouse brain and, thus, suppresses the formation of psychological addiction to methamphetamine and morphine. The possible use of these substances in narcological clinical practice is discussed.