Pharmacogenetics of Addiction Therapy

2014 ◽  
pp. 589-624 ◽  
Author(s):  
David A. Nielsen ◽  
Ellen M. Nielsen ◽  
Teja Dasari ◽  
Catherine J. Spellicy
Keyword(s):  
Addiction Therapy

Addiction Therapy Advances May Pave Way for Primary Care Role

2010 ◽  
Vol 43 (18) ◽  
pp. 1-32
Author(s):  
SHARON WORCESTER
Keyword(s):  
Primary Care ◽  
Addiction Therapy

scholarly journals Cannabinoid-Induced Conditioned Place Preference, Intravenous Self-Administration, and Behavioral Stimulation Influenced by Ghrelin Receptor Antagonism in Rats

2021 ◽  
Vol 22 (5) ◽  
pp. 2397
Author(s):  
Chrysostomos Charalambous ◽  
Tereza Havlickova ◽  
Marek Lapka ◽  
Nina Puskina ◽  
Romana Šlamberová ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Fixed Ratio ◽  
Place Preference ◽  
Self Administration ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Ghrelin Receptor ◽  
Addiction Therapy ◽  
Significant Efficacy ◽  
Lever Pressing

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.

scholarly journals Association of DRD2 (rs 1799732), ANKK1 (rs1800497), DAT (rs28363170), DRD4 (exon 3 - VNTR) gene polymorphisms in the context of relapses in therapy.

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jolanta Chmielowiec ◽  
Agnieszka Boroń
Keyword(s):  
Dopamine Receptor ◽  
Treatment Center ◽  
Control Group ◽  
Special Role ◽  
Psychoactive Substances ◽  
Vntr Polymorphism ◽  
Genotype Frequencies ◽  
Addiction Therapy ◽  
Pcr Method ◽  
Therapy Center

Abstract Introduction: Disorders in the field of reward system neurotransmission are mentioned as one of the most important causes of addiction. Genetic variation is assigned a special role. The literature on the subject mentions primarily the genes of dopamine neurotransmission: DAT (dopamine transporter), DRD2 (dopamine receptor D2), DRD4 (dopamine receptor D4). However, so far there are few literature reports on these genes in the context of innovators in addiction therapy. The aim: Analysis of the relationship between the variability of specific polymorphisms in the DRD2 (rs1799732), ANKK1 (rs1800497), DAT (rs28363170), DRD4 (exon 3 - VNTR) genes with the occurrence of relapses in people addicted to psychoactive substances. Material and methods: The research was carried out on a group of 301 people addicted to psychoactive substances staying in an addiction therapy center in Lubuskie and Zachodniopomorskie voivodships in Poland. The control group consisted of 301 people with no diagnosed addiction to psychoactive substances nor mental disorders. The study of polymorphisms DRD2 (rs 1799732), ANKK1 (rs1800497) was performed by real-time PCR method; whereas DAT (rs28363170), DRD4 (exon 3 - VNTR) was genotyped by PCR and the amplified products were visualized using ethidium bromide stained gel electrophoresis (3% agarose) and UV photography. Results: This study showed that in addicts genotype frequencies of the VNTR polymorphism in the third exon of human DRD4 were as follow: S/L in 33.55%, S/S - 63.12% and L/L 3.32%; while in the control group S/L - 32.56%, S/S - 58.8 % and L/L -8.6% (χ2 = 7.617, p = 0.022). Significant differences in the frequency of DRD2 gene polymorphism rs1799732 were observed (frequency of alleles; χ2 = 5.48, p = 0.0192) and DRD4 VNTR polymorphism (χ2 = 7.687, p = 0.021) between the addicted to psychoactive substances who have a one-time stay in an inpatient treatment center and the control group.

Treatment and outcomes at Takiwasi Center, a Peruvian therapeutic community: identifying patient-related indicators

2019 ◽  
Vol 40 (2) ◽  
pp. 93-106
Author(s):  
Victoria Defelippe ◽  
Anna Schlütter ◽  
Annelen Meriaan ◽  
Bjorn Winkens ◽  
Veronika Kavenská ◽  
...  
Keyword(s):  
Addiction Treatment ◽  
Therapeutic Community ◽  
Treatment Options ◽  
Multivariable Analysis ◽  
Significant Risk ◽  
Drop Out ◽  
Health Concern ◽  
Content Type ◽  
Addiction Therapy ◽  
Treatment Centre

Purpose Substance abuse is a major public health concern, with over millions of people suffering from it worldwide. Although there is an abundance of treatment options, many of these rehabilitative trajectories are subject to “drop-out”. In addition, “drop-out” is a significant risk factor for relapse. There is an urgent demand for effective treatment, which would enable patients to reduce abuse and prevent relapse. Takiwasi is an addiction treatment centre that combines traditional Amazonian plant medicine with conventional western medicine and psychotherapy. The purpose of this paper is to explore whether socio-demographics factors, such as education level and occupation, psychiatric comorbidities and primary drug use, are associated with treatment non-completion of Ayahuasca (AYA)-assisted addiction therapy. Design/methodology/approach Data on the first treatment episode of 121 patients were collected from the patient database from the years 2012 to 2017. To determine whether there is an association between the variables of interest and treatment non-completion, a χ2 analysis and a logistic regression analysis were performed. Findings Of the 121 patients analysed, 48.2 per cent completed their treatment, whilst 51.8 per cent did not. Students compared to those who are employed showed significantly higher odds for treatment non-completion (p=0.006; OR=3.7; 95% CI=1.5–9.6). Other variables in the multivariable analysis showed no significant relationship with treatment non-completion. While several limitations restricted the study, the findings suggest that the AYA-assisted treatment in Takiwasi may benefit from additional support for patients who are students. Moreover, it is advised to conduct more long-term follow-up of patients in order to gain better insight into the outcome of treatment at an AYA-assisted treatment centre. Originality/value It appears that AYA-assisted therapy in a therapeutic community is a feasible type of treatment for addiction, for which further studies should elucidate the role of motivation in relation to socio-demographic factors and type of addiction in the risk of treatment non-completion.

scholarly journals Long-acting cocaine hydrolase for addiction therapy

2015 ◽  
Vol 113 (2) ◽  
pp. 422-427 ◽  
Author(s):  
Xiabin Chen ◽  
Liu Xue ◽  
Shurong Hou ◽  
Zhenyu Jin ◽  
Ting Zhang ◽  
...  
Keyword(s):  
Half Life ◽  
Addiction Treatment ◽  
Catalytic Efficiency ◽  
Cocaine Addiction ◽  
General Observation ◽  
Exogenous Enzyme ◽  
Normal Functions ◽  
Biological Half Life ◽  
Addiction Therapy ◽  
Long Acting

Cocaine abuse is a world-wide public health and social problem without a US Food and Drug Administration-approved medication. An ideal anticocaine medication would accelerate cocaine metabolism, producing biologically inactive metabolites by administration of an efficient cocaine-specific exogenous enzyme. Our recent studies have led to the discovery of the desirable, highly efficient cocaine hydrolases (CocHs) that can efficiently detoxify and inactivate cocaine without affecting normal functions of the CNS. Preclinical and clinical data have demonstrated that these CocHs are safe for use in humans and are effective for accelerating cocaine metabolism. However, the actual therapeutic use of a CocH in cocaine addiction treatment is limited by its short biological half-life (e.g., 8 h or shorter in rats). Here we demonstrate a novel CocH form, a catalytic antibody analog, which is a fragment crystallizable (Fc)-fused CocH dimer (CocH-Fc) constructed by using CocH to replace the Fab region of human IgG1. The CocH-Fc not only has a high catalytic efficiency against cocaine but also, like an antibody, has a considerably longer biological half-life (e.g., ∼107 h in rats). A single dose of CocH-Fc was able to accelerate cocaine metabolism in rats even after 20 d and thus block cocaine-induced hyperactivity and toxicity for a long period. Given the general observation that the biological half-life of a protein drug is significantly longer in humans than in rodents, the CocH-Fc reported in this study could allow dosing once every 2–4 wk, or longer, for treatment of cocaine addiction in humans.

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