Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin's/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin's/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.

• Klíčová slova
• addiction, cannabinoids, ghrelin signaling, growth hormone secretagogue receptor type A (GHS-R1A), nicotine/tobacco, opioids, preclinical and clinical research, review, stimulants,
• MeSH
• biologické markery MeSH
• genetická predispozice k nemoci MeSH
• ghrelin metabolismus   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• náchylnost k nemoci MeSH
• nikotin škodlivé účinky   MeSH
• poruchy spojené s užíváním psychoaktivních látek etiologie   metabolismus   MeSH
• posilování (psychologie) MeSH
• receptory ghrelinu metabolismus   MeSH
• signální transdukce * MeSH
• stimulanty centrálního nervového systému škodlivé účinky   MeSH
• užívání tabáku škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• ghrelin MeSH
• GHRL protein, human MeSH Prohlížeč
• Ghsr1a protein, human MeSH Prohlížeč
• nikotin MeSH
• receptory ghrelinu MeSH
• stimulanty centrálního nervového systému MeSH

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

• Klíčová slova
• WIN55,212-2, addiction, behavioral stimulation, conditioned place preference, ghrelin antagonism, intravenous self-administration, synthetic cannabinoid, tetrahydrocannabinol (THC),
• MeSH
• autoaplikace MeSH
• chování zvířat účinky léků   MeSH
• glycin analogy a deriváty   farmakologie   MeSH
• intravenózní podání MeSH
• kanabinoidy aplikace a dávkování   farmakologie   MeSH
• krysa rodu Rattus MeSH
• operantní podmiňování účinky léků   MeSH
• podmiňování (psychologie) účinky léků   MeSH
• posilování (psychologie) MeSH
• potkani Wistar MeSH
• receptory ghrelinu antagonisté a inhibitory   MeSH
• triazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• Ghsr1a protein, rat MeSH Prohlížeč
• glycin MeSH
• kanabinoidy MeSH
• N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
• receptory ghrelinu MeSH
• triazoly MeSH