New frontiers in alcoholism and addiction treatment.

Drug addiction and alcoholism are behavioural disorders characterized by a profound alteration of several brain circuits induced by chronic drug use. Their treatment is yet based on empiricism and today only few pharmacological strategies are fully effective to control both drug use and relapse. The present paper reviews the most updated pharmacotherapies able to contrast both alcoholism and drug addiction including the new patented drugs and the future therapeutic trends.

Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: preliminary results of an open randomized study.

An open randomized study lasting 12 months was performed to evaluate the efficacy of methadone or buprenorphine to suppress alcohol use in two hundred and eighteen heroin addicts with alcohol dependence. Daily maintenance doses of methadone were 80, 120, 160, and 200 mg/day, while doses of buprenorphine were 8, 16, 24, and 32 mg/day. As expected, both treatments were able to reduce both heroin use and addiction severity (measured with ASI interview). However, although both medications were able to suppress alcohol use, the highest dose of buprenorphine was better than the highest dose of methadone, in reducing alcohol craving, ethanol intake (measured as daily number of drinks), and the ASI subscale of alcohol use. The mechanism underlying the effects of the opioid maintenance therapy on the reduction of alcohol intake is still unclear. The results of the present study may represent the first clinical evidence of the potential effective use of the highest doses of buprenorphine for the suppression of ethanol intake in heroin addicts with alcohol dependence.

Gamma-hydroxybutyrate reduces both withdrawal syndrome and hypercortisolism in severe abstinent alcoholics: an open study vs. diazepam.

In 42 alcoholic inpatients we performed an open randomized study to compare the effects of diazepam and gamma-hydroxybutyrate (GHB) on the suppression of severe alcohol withdrawal syndrome and hypercortisolism. Both diazepam (.5 mg/kg bodyweight, q.i.d.) and GHB (50 mg/kg bodyweight, q.i.d.) were orally administered for three weeks. During all study period, GHB was more able than diazepam in reducing both withdrawal syndrome and hypercortisolism. These effects were evident during the first week of treatment and persisted throughout the study period. The results confirm a strict correlation between high levels of plasma cortisol and alcohol withdrawal symptoms and they show a slight superiority of GHB over diazepam in the suppression of both ethanol withdrawal and hypercortisolism. Taken together, our data suggest that GHB may act as potent anti-withdrawal agent in severe abstinent alcoholics.

Combination of olanzapine with opioid-agonists in the treatment of heroin-addicted patients affected by comorbid schizophrenia spectrum disorders.

The objective of this study was to evaluate the efficacy of olanzapine (OLA) in heroin-dependent patients affected by comorbid schizophrenia spectrum disorders (SSD). Sixty-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for heroin dependence and the criteria for SSD (schizophrenia and schizotypal and schizoaffective-bipolar disorders) were treated in a 12-week prospective observational trial of substitution treatment in combination with OLA or typical antipsychotic haloperidol. Patients were included into 2 subgroups, in relationship with treatment, for the evaluation of the end points at week 12: group 1, SSD treated with OLA (35 patients); group 2, SSD treated with haloperidol (26 patients). Efficacy measures were retention in treatment, Symptoms Checklist-90 score changes, negative urinalyses results, and craving reduction. The rate of patients who remained in treatment at week 12 in group 1 SSD, treated with OLA, was significantly higher (32[91.4%]) than that of group 2 SSD (13 [50%]), treated with the typical antipsychotic (P < 0.001). The decrease in Symptoms Checklist-90 total scores from baseline, as expression of an improvement in comorbid psychopathology in the patients who completed the treatment, was significantly more consistent in group 1 than in group 2 patients (P < 0.01). Among the patients who remained in treatment, 64.4% achieved early full substance abuse remission, whereas 35.6% achieved partial substance abuse remission, with a significant difference between 1 (78.13%) and 2 (46.1%) treatment subgroups (P = 0.04). Although obtained by an observational-open clinical study with multiple limitations, our findings suggest that OLA may be able to increase retention and negative urinalyses rates during opioid agonist maintenance treatment in the patients with SSD and to improve psychopathology symptoms and tolerability in these dually diagnosed heroin addicts. Preliminary accurate diagnostic assessment and appropriate psychoactive medication in addicted patients affected by schizophrenia and schizotypal and schizoaffective-bipolar disorders seem to obtain less adverse effects and a more successful outcome of drug dependence treatment.

Chronic cannabis use does not affect the normalization of hypothalamic-pituitary-adrenal (HPA) axis induced by methadone in heroin addicts.

The hypothalamic-pituitary-adrenal (HPA) axis activity is usually altered by heroin use. In the present study we evaluated in one hundred twenty-one heroin addicts the effects of marijuana smoking on the normalization of HPA axis upon methadone treatment. The study showed that in heroin addicts who are chronic cannabis smokers a treatment with methadone lasting 12 months was able to normalize both plasma corticotropin (ACTH) and cortisol levels, as well as to control both heroin withdrawal symptoms and opioid craving. As expected in the same group of patients marijuana smoking and its craving were not reduced by methadone treatment. Our data confirm that methadone treatment outcomes are not modified by cannabis use and they add in the literature the evidence that chronic cannabis use is not able to affect the normalization of HPA axis upon methadone treatment in heroin addicts.

Comparing treatments of alcoholism on craving and biochemical measures of alcohol consumptionst.

An open randomized study was conducted to compare different treatments of alcoholism on ethanol intake, craving, and on biochemical measures of alcohol consumptions. Eighty-six alcoholics were abstinent for a mean of two weeks prior to random assignment to g-hydroxybutyrate (GHB, 50 mg/kg of body weight t.i.d), naltrexone (NTX, 50 mg/day) or disulfiram (DSF, 200 mg/ day) treatment for 12 months. All treatments were equally effective in reducing alcohol intake and in maintaining abstinence. In all patients, the treatments were able to reduce both craving and the altered biological markers of alcohol abuse. The maximum effects were observed in GHB-treated patients. The results of the present study suggest that GHB might act both as anticraving and cellular protector agent.