The therapeutic effect of N-acetylcysteine as an add-on to methadone maintenance therapy medication in outpatients with substance use disorders: A randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Patients with substance use disorders (SUD) under methadone maintenance therapy (MMT) are susceptible to a number of complications (psychological and metabolic disorders). Evidence studies have shown the roles of the glutamatergic system in addiction. N-Acetylcysteine (NAC) enhances extracellular glutamate, and is effective in the treatment of neuropsychiatric disorders. We assessed oral NAC as an add-on to MMT medication for the treatment of SUD. METHODS: In the current randomized, double-blind, placebo-controlled clinical trial, outpatients with SUD under MMT who were 18-60 years old received 2400 mg/day NAC (n = 30) or placebo (n = 30) for 12 weeks. Psychological status and metabolic biomarkers were assessed at baseline and the end of the trial. RESULTS: Compared with the placebo group, NAC treatment resulted in a significant improvement in depression score (ß -2.36; 95% CI, -3.97, -0.76; p = .005), and anxiety score (ß -1.82; 95% CI, -3.19, -0.44; p = .01). Furthermore, NAC treatment resulted in a significant elevation in total antioxidant capacity levels (ß 72.28 mmol/L; 95% CI, 11.36, 133.19; p = .02), total glutathione (GSH) levels (ß 81.84 µmol/L; 95% CI, 15.40, 148.28; p = .01), and a significant reduction in high-sensitivity C-reactive protein levels (ß -0.89 mg/L; 95% CI, -1.50, -0.28; p = .005), and homeostasis model of assessment-insulin resistance (ß -0.33; 95% CI, -0.65, -0.009; p = .04), compared with the placebo group. CONCLUSION: In the current study, improvement in depression and anxiety symptoms as well as some metabolic profiles with NAC treatment for 12 weeks in outpatients with SUD under MMT was detected.

The Effects of Probiotic Supplementation on Opioid-Related Disorder in Patients under Methadone Maintenance Treatment Programs.

Introduction: Patients under methadone maintenance treatment programs (MMTPs) are susceptible to numerous complications (e.g., mental and metabolic disorders). This study evaluated the effects of probiotics on clinical symptoms, biomarkers of oxidative stress, inflammation, insulin resistance, and serum lipid content in patients receiving MMTPs. Materials and Methods: A randomized, double-blind, placebo-controlled trial was conducted among 70 patients receiving MMTPs to receive either 1.8 × 109 CFU/day probiotics (n = 35) or placebo (n = 35) for 12 weeks. Clinical symptoms and metabolic profiles were measured before and after the intervention in patients receiving MMTPs. Results: Compared with the placebo group, probiotic supplementation resulted in a significant improvement in the severity of depression (P < 0.05). In addition, probiotic administration significantly decreased fasting plasma glucose (FPG), total cholesterol, and low-density lipoprotein cholesterol (LDL cholesterol) (P < 0.05). Furthermore, probiotics resulted in a significant reduction in high-sensitivity C-reactive protein (hs-CRP) and a significant elevation in total antioxidant capacity (TAC) and total glutathione (GSH) levels (P < 0.05). Conclusion: Treatment with probiotics for 12 weeks to patients receiving MMTPs had beneficial effects on symptoms of depression, as well as several metabolic profiles. Clinical Trial Registration: this study was registered in the Iranian website (https://www.irct.ir) for clinical trials registration (https://fa.irct.ir/trial/46363/IRCT20170420033551N9). The registration date is March 22, 2020.

The effect of vitamin D supplementation on tobacco-related disorders in individuals with a tobacco use disorder: a randomized clinical trial.

Vitamin D deficiency in cigarette smokers (CS) might associate with several complications, including metabolic deficits, depression and anxiety. This study evaluated the effects of vitamin D on mental health symptoms, nicotine misuse, and biomarkers of metabolic diseases in individuals with a tobacco use disorder. A randomized, double-blind, placebo-controlled trial was conducted with 60 CS subjects receiving either 50,000 IU vitamin D supplements (n = 30) or placebo (n = 30) every 2 weeks for 24-weeks. Nicotine misuse, mental health scale, and metabolic parameters were measured before and after the intervention in the CS subjects. Compared with the placebo-group, after the 24-weeks intervention, serum 25 (OH) vitamin D levels increased in the intervention group (ß 2.96; 95% CI, 0.91, 5.01; P = 0.006). In addition, vitamin D supplementation significantly improved Beck Depression Inventory (BDI) (ß -2.06; 95% CI, -3.84, -0.28; P = 0.02). In addition, vitamin D administration significantly decreased fasting plasma glucose (FPG) (ß -4.56; 95% CI, -8.94, -0.19; P = 0.04), insulin (ß -0.50; 95% CI, -0.88, -0.13; P = 0.009), and homeostasis model of assessment-estimated insulin resistance (HOMA-IR) levels (ß -0.21; 95% CI, -0.33, -0.08; P = 0.001). Furthermore, vitamin D resulted in a significant elevation in total antioxidant capacity (TAC) (ß 81.20; 95% CI, 18.30, 144.11; P = 0.01), and plasma glutathione (GSH) levels (ß 73.05; 95% CI, 18.56, 127.54; P = 0.01), compared with the placebo-group. Administration of vitamin D for 24-weeks to CS subjects had beneficial effects on symptoms of depression and several metabolic biomarkers. While this preliminary study suggests that vitamin D might have beneficial effects, its clinical efficacy in individuals with a tobacco use disorder should be further validated in future clinical trials.

The effect of crocin (the main active saffron constituent) on the cognitive functions, craving, and withdrawal syndrome in opioid patients under methadone maintenance treatment.

Individuals under methadone maintenance treatment (MMT) programs are susceptible to several complications, including withdrawal syndrome, craving, and cognitive deficits. This study was designed to elevate the effect of crocin administration on withdrawal syndrome, craving, and cognitive function in subjects under MMT programs. It was a clinical trial that was conducted among 60 patients referred to Soltan Mirahmad Clinic for addict patients in Kashan, Iran. The patients were allocated to two groups including placebo and intervention groups. The intervention group received 30 mg/day crocin (n = 30) and placebo (n = 30) once a day, in 12 weeks. Withdrawal syndrome, craving, and cognitive function parameters were measured before and after the intervention in subjects under MMT programs. Compared with the placebo group, crocin resulted in a significant improvement in craving score (p = .03), and withdrawal symptoms score (p = .01) in the intervention group. In addition, crocin supplementation did not affect cognitive function parameters (e.g., TMT, FAS test, and DGSP score). Overall, crocin supplementation for 12 weeks to patients under MMT programs had beneficial effects on craving and withdrawal symptoms score, but did not affect the cognitive function parameters.