Investigation Of Psychological Status Of Ex-drug Addicts And Evaluation On The Effect Of Neurotransmitter-precursor-supplement Intervention

Illicit-drug abuse is a serious social and public health issue. It not only damages the national economy and human health, but also harms social stability. Globally, about 210 million people use illicit drugs per year, and almost 200,000 of these users die from drugs. In China, since the 1980s illicit-drug abuse has been resurgent and shown a spreading tendency. The number of registered illicit drug users grew from approximately 70,000 in 1990 to 1.33 million by the end of 2009, among whom 73.2% abused heroin.A central problem in treating heroin dependence is relapse, which is associated with various factors including environmental and self-assertive factors. Among them, psychological factor plays an important role in relapse. Previous research indicated that as the mood got worse, the craving woke up rate reached 74.89%. Thus, investigating and improving the psychological status of ex-drug addicts have significance in relapse prevention.Although the underling mechanism of addiction and relapse remains unclear, the mesolimbic reward system is believed to have a considerable effect on heroin-related problems and relapse. Nearly all drugs of abuse (including heroin) have some effects on the reward system either by directly influencing the activity of dopamine in this system or by altering the action of other neurotransmitters such as y-Aminobutyric acid, serotonergic, and cholinergic neurotransmitters to exert an influence over the pathway. 'reward-deficiency syndrome'is a hypothesis for explaining addiction and relapse. This hypothesis considers that people with imbalance of mesolimbic reward system including insufficient receptors and absence of transmitters may get less satisfaction with things usually interested, and consequently tend to abuse drugs for seeking an enhanced stimulation of reward pathways.Therefore, reduced dopamine or decreased dopamine receptor in the reward system may lead to drug seeking according to 'reward-deficiency syndrome' hypothesis. With long-term or repeated use of heroin or other drugs, the associated neurotransmitters in the brain circuits including dopamine, GABA and serotonin were depleted or could be produced less than they should be. Moreover, some studies showed that drug addicts had poor nutritional status, which further lessened the impacts of neurotransmitters on the reward circuit. Thus addicts may seek drug to enhance stimulation. Several studies suggested that ingestion of dietary precursors of certain neurotransmitters could increase their levels in the brain. In addition, some studies indicated that dietary neurotransmitter precursors such as tryptophan and lecithin may have potential helpful in treating sleep disorders and mood disorders.Therefore, we hypothesized that the precursors of key neurotransmitters, including tyrosine, lecithin, L-glutamine, and L-5-hydroxytryptophan, could be useful in alleviating symptoms of addicts and thus in relapse prevention. We conducted the study in order to investigate the psychological status of ex-drug addicts and explore the effect of neurotransmitter precursors supplement intervention for relapse prevention. The research includes the following three parts:Part I Analysis of psychological status and risk factors among ex-drug addictsObjective:To investigate psychological status of ex-drug addicts, to explore associated risk factors of ex-drug addicts'mood, and to help prevent relapse.Methods:We utilized a purposive sampling method to select 1270 persons subjected to reeducation through labor,894 of who were ex-drug addicts, from reeducation-through-labor camps in Wuhan. We investigated the following information: demographics, home background, psychological status, personality traits, and other aspects. Logistic regression analysis, general linear model analysis, factor analysis and structural equation models were used to explore associated risk factors of mood among ex-drug addicts subjected to reeducation through labor. All analyses were done with SPSS 12.0 and AMOS software.Results:The average score of total mood disturbance (TMD) of all persons subjected to reeducation through labor was 51.1±37.1, and 54.3% of them were in significant psychological stress. The score of ex-drug addicts reached 52.1±36.8,55.8% of who were in significant psychological stress. The score of other participants was 48.6±37.5,50.5% of who were in significant psychological stress. Multiple logistic regression indicated that male ex-drug addicts had lower risk to be in significant psychological stress than female ex-drug addicts (male vs. female:odds ratios [OR]= 0.47,95% confidence interval [CI]= 0.32-0.71, P<0.001). As compared with unmarried ex-drug addicts, married and separated/divorced/widowed individuals had higher risk to be in significant psychological stress (married vs. unmarried:OR=1.84,95% CI=1.16-2.93, P=0.010; separated/divorced/widowed vs. unmarried:OR=2.06,95% CI=1.29-3.28, P=0.002). Additionally, anger, hostility, self-aggression, action-impulsion and cognitive impulsion were risk factor for psychological status (OR=1.02,95% CI =1.01-1.03, P=0.004; OR=1.05,95% CI=1.03-1.06, P<0.001; OR=1.02,95% CI =1.01-1.03, P=0.001; OR=1.03,95% CI=1.02-1.04, P<0.001; and OR=1.02,95% CI =1.00-1.03, P=0.022, respectively). General linear model analysis indicated that age, gender, marriage status, physical aggression, verbal aggression, anger, hostility, self-aggression and action-impulsion could affect psychological status of ex-drug addicts. Coefficients of regression of age, female, married, separated/divorced/widowed, physical aggression, verbal aggression, anger, hostility, self-aggression and action-impulsion were 0.348 (P=0.033),-6.590 (P=0.003),5.779 (P=0.034),7.718 (P =0.005),-0.145 (P=0.034),-0.251 (P=0.002),0.302 (P<0.001),0.571 (P<0.001),0.334 (P<0.001), and 0.431 (P<0.001). Results of structural equation models suggested that factor named aggression and impulsion dominating physical aggression, verbal aggression, anger, hostility, self-aggression and action-impulsion had greatest impact on psychological status (standardized regression coefficient=0.600)Conclusion:Lots of ex-drug addicts subjected to reeducation through labor were in significant psychological stress. Gender, marital status, whether parents living, and aggressive and impulsive personality traits had direct or indirect effect on psychological status among ex-drug addicts subjected to reeducation through labor.PartⅡThe effect of neurotransmitter precursors on maintenance of morphine conditioned place preference in ratsObjective:To assess the effects of tyrosine and phosphatidylcholine on the maintenance of morphine-induced conditioned place preference (CPP) in rats.Methods:Rats were injected morphine (5mg/kg, one time per day, s.c.) for 7 continuous days for establishing a CPP morphine dependent model. In the CPP involuting phase, the rats were treated with tyrosine (200 or 400 mg/kg, one time per day, i.g.) or lecithin (100 or 200 mg/kg, one time per day, i.g.), or the combination (tyrosine 200 mg/kg+soy lecithin 100mg/kg, or tyrosine 400 mg/kg+soy lecithin 200mg/kg, one time per day, i.g.) for 14 continuous days. We observed the effect of tyrosine and lecithin and the combination on maintenance of morphine induced CPP.Results:On the 14th day after stopped using morphine, the mean time rats spent in the drug-paired place were 45.78±14.61 and 248.78±65.29s for rats in the blank group and model group, respectively. The mean conditioning time was 96.22±51.75s for groups of tyrosine 400 mg/kg (P=0.471 as compared with blank group; P=0.035 as compared with model group). For group of soy lecithin soy lecithin 200mg/kg, the mean conditioning time on the 14th day after stopped using morphine, was 100.78±43.41s (P =0.401 as compared with blank group; P=0.029 as compared with model group). The mean conditioning scores of the two combination groups (tyrosine 200 mg/kg+soy lecithin 100mg/kg, and tyrosine 400 mg/kg+soy lecithin 200mg/kg) on the 14th day after stopped using morphine was 168.00±61.23 and 172.89±40.88s, respectively (P =0.092 and P=0.080 as compared with blank group, respectively; P=0.259 and P=0.289 as compared with model group, respectively). Conclusion:Tyrosine, soy lecithin and combination of tyrosine and soy lecithin could reduce the time rats spent in the drug-paired compartment, which indicated that these supplements could attenuate maintenance of morphine induced CPP and suggested its potential use in relapse prevention among human.Part III Study of neurotransmitter-precursor-supplement intervention in alleviating withdrawal syndromes and mental symptoms among detoxified heroin addictsObjective:To evaluate the effects of supplementing tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan (5-HTP) on heroin withdrawal syndromes and mental symptoms among detoxified heroin addicts.Methods:In a cluster-randomized placebo-controlled trial, we recruited 83 detoxified heroin addicts from an detoxification center in Wuhan. The combination of tyrosine, lecithin, L-glutamine, and 5-HTP for the intervention group and the placebo for the control group were administered. The sleep status and withdrawal symptoms were examined daily throughout the study, and mood states were monitored pre- and post-intervention. We used the 2-sample t test to compare the changes between the 2 groups at baseline and day 6. For insomnia symptoms and withdrawal symptoms, the scores were compared between the 2 treatment groups over time by using mixed linear models.Results:For insomnia scores over time there was a significant interaction effect of time and treatment (b=-1.595, P<0.001, b represents the estimated slope parameter). The results indicated that participants in the intervention group had a significantly greater reduction of insomnia scores over time. Similarly, there was also a significant interaction effect of time and treatment (b=-1.348, P=0.010) for withdrawal scores over time, suggesting that participants in the intervention group had a significantly greater reduction of withdrawal scores over time. Additionally, participants who received nutrients experienced greater mean (SD) reduction (day 6 scores minus baseline scores) in their tension-anxiety (-4.27 [7.27] vs.-1.10 [4.84], P=0.02), depression-dejection (-8.12 [12.13] vs.-3.02 [7.40], P=0.02), anger-hostility (-5.05 [10.16] vs.-0.52 [4.97], P =0.01), fatigue-inertia (-4.78 [7.67] vs.-1.05 [4.37], P=0.01), and TMD (-25.93 [40.19] vs.-7.10 [20.76], P=0.01) and a greater mean (SD) increase in their vigor-activity (2.49 [4.82] vs.0.10 [3.34], P=0.01) as compared with the control group.Conclusion:Neurotransmitter-precursor-supplement intervention appears to be effective in alleviating the withdrawal and mood symptoms and could be a supplementary method for patients'recovery from heroin addiction.Innovation aspects of the present study:1. We systematically investigated psychological status of ex-drug addicts subjected to reeducation through labor and explored associated risk factors affecting their moods. Based on the information, we constructed logistic regression, general linear model analysis and structural equation model and found the direct or indirect factors affecting ex-drug addicts'psychological status.2. We used neurotransmitter precursors (tyrosine and phosphatidylcholine) to intervene in rats and evaluated the effects of the neurotransmitter precursors on the maintenance of morphine-induced conditioned place preference (CPP) in rats.3. We supplemented neurotransmitter precursors (tyrosine, lecithin, L-glutamine and L-5-hydroxytryptophan) for detoxified heroin addicts and evaluated the effects of the supplements on heroin withdrawal syndromes and mental symptoms among detoxified heroin addicts.