Abstract Background This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol ...dependence. Methods 208 patients were randomized to disulfiram (250 mg/day), naltrexone (100 mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol. Results Few safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiram–naltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol. Conclusion There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram–naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients.
We present the first record of Rhizophora mangle (Malpighiales: Rhizophoraceae) as a host of Acalles sablensisBlatchley, 1920 (Coleoptera: Curculionidae: Cryptorhynchinae) in the Ramsar site No. 1602 ...of the Mangroves and Wetlands of Tuxpan. The presence was recorded of dead Rhizophora mangle propagules that presented perforations in the bark. Beetles of the family Curculionidae was found within the propagules and identified as Acalles sablensis. This species has previously only been recorded in Cape Sable and Chokoloskee, Florida, USA, in 1920 and 1922 in dead branches of Sideroxylon celastrina (Kunth) T. D. Penn (Ericales: Sapotaceae) (Blatchley 1920, 1922). This study represents the first report of this curculionid species in Mexico.
Subjective effects of alcohol in alcoholics treated with naltrexone or placebo were compared.
In a previously reported double-blind clinical trial of 50 mg/day of naltrexone or placebo for treatment ...of alcoholism, 36 of 70 detoxified male veterans deviated from abstinence. Of these 36, 29 subsequently reported on the subjective effects of drinking during the trial.
A larger proportion of naltrexone-treated subjects (seven of 12) than placebo-treated subjects (two of 17) reported that the "high" produced by alcohol during the study was significantly less than usual. The naltrexone-treated subjects also drank less alcohol than the placebo-treated subjects during the first drinking episode. There was no difference between groups in reported intoxication, craving, memory, or loss of temper.
The lower alcohol consumption by the naltrexone-treated subjects may have resulted from naltrexone's blockage of the pleasure produced by alcohol.
Background: Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the ...rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence.
Methods: The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (
n=40). Topiramate was titrated gradually over 8 weeks to a dose of 200
mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT).
Results: Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (
Z=2.67,
P=0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (
χ
2=3.9, d.f.=1,
P=0.05).
Conclusion: Topiramate may be effective for the treatment of cocaine dependence.
The authors tested the efficacy of individual psychotherapy in the rehabilitation counseling of psychiatrically symptomatic opiate-dependent patients during methadone maintenance treatment in ...community programs.
Volunteers in three community programs were randomly assigned to 24 weeks of counseling plus supplemental drug counseling or to counseling plus supportive-expressive psychotherapy. Follow-ups were done 1 and 6 months after treatment ended. A total of 84 subjects were evaluated at both follow-up points.
During the study the patients receiving supportive-expressive psychotherapy and those receiving drug counseling had similar proportions of opiate-positive urine samples, but the patients receiving supportive-expressive psychotherapy had fewer cocaine-positive urine samples and required lower doses of methadone. One month after the extra therapy ended both groups had made significant gains, but there were no significant differences between groups. By 6-month follow-up many of the gains made by the drug counseling patients had diminished, whereas most of the gains made by the patients who received supportive-expressive psychotherapy remained or were still evident; many significant differences emerged, all favoring supportive-expressive psychotherapy.
Psychotherapy can be delivered to psychiatrically impaired patients in community methadone programs. Additional counseling is associated with early benefits comparable to those from psychotherapy, but these gains are not sustained. The gains associated with psychotherapy persist and in some cases strengthen for at least 6 months after the end of therapy.
Twin, family and adoption studies have suggested that vulnerability to opioid dependence may be a partially inherited trait (Cadoret et al., 1986; Merikangas et al., 1998; Tsuang et al., 1998, 2001). ...Studies using animal models also support a role for genetic factors in opioid dependence, and point to a locus of major effect on mouse chromosome 10 (Berrettini et al., 1994; Alexander et al., 1996), which harbors the mu opioid receptor gene (Mor1) (Kozak et al., 1994). The gene encoding the human mu opioid receptor (OPRM1) is thus an obvious candidate gene for contributing to opioid dependence. A recent report (Hoehe et al., 2000) found a significant association between a specific combination of OPRM1 single nucleotide polymorphisms (SNPs) and substance dependence.
In the current study, we genotyped 213 subjects with severe opioid dependence (89 African-Americans, 124 European-Americans) and 196 carefully screened "supercontrol" subjects (96 African-Americans, 100 European-Americans) at five SNPs residing in the OPRM1 gene. The polymorphisms include three in the promoter region (T-1793A, -1699T insertion and A-1320G) and two in exon 1 (C+17T Ala6Val and A+118G Asp40Asn).
Statistical analysis of the allele frequency differences between opioid-dependent and control subjects for each of the polymorphisms studied yielded P values in the range of 0.444-1.000. Haplotype analysis failed to identify any specific combination of SNPs associated with the phenotype.
Despite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans.
Abstract Background Extended-release naltrexone (XR-NTX), is an effective treatment for opioid use disorder but is rarely initiated in US prisons or with criminal justice populations. Mobile ...treatment for chronic diseases h
as
been implemented in a variety of settings. Mobile treatment may provide an opportunity to expand outreach to parolees to surmount barriers to traditional clinic treatment. Methods Male and female prisoners (240) with pre-incarceration histories of opioid use disorder who are within one month of release from prison will be enrolled in this randomized clinical trial. Participants are randomized to one of two study arms: 1) XR-NTX-OTx One injection of long-acting naltrexone in prison, followed by 6 monthly injections post-release at a community opioid treatment program; or 2) XR-NTX + MMTx One injection of long-acting naltrexone in prison followed by 6 monthly injections post-release at the patient
'
s place of residence utilizing mobile medical treatment. The primary outcomes are: treatment adherence; opioid use; criminal activity; re-arrest; reincarceration; and HIV risk-behaviors. Results We describe the background and rationale for the study, its aims, hypotheses, and study design. Conclusions The use of long-acting injectable naltrexone may be a promising form of treatment for pre-release prisoners. Finally, as many individuals in the criminal justice system drop out of treatment, this study will assess whether treatment at their place of residence will improve adherence and positively affect treatment outcomes. ClinicalTrials.gov : NCT02867124
OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during ...cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the nondrug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.
Multi-length scale modeling is performed to (i) predict the carburized case depth of SAE8620 steel gears by solving the Fick’s second law of diffusion, (ii) model the martensitic microstructure ...evolution in a grain inside the carburized case as well as to study the effect of stress cycling on retained austenite (RA) and martensite using a 3D phase-field model, (iii) simulate the effect of carburization and different RA contents on macroscale fatigue behavior of SAE8620 steel spur gear using the finite element method. The diffusion model predicts that the case depth increases with increasing heat treatment time and temperature. The phase-field simulations show that RA can transform to martensite during fatigue loading, where the extent of the transformation will depend on the type of stresses applied, i.e. stresses in a high stress regime or low stress regime of fatigue loading. Reverse transformation of martensite to austenite is also observed in low RA sample under high stress regime. The macroscale simulations show that the carburized case with high RA gives rise to better fatigue life compared to that with low RA.
Aims. Substance‐abusing populations perform poorly on decision‐making tasks related to delay and risk. These tasks include: (1) the Delay Discounting Procedure (DDP), in which choices are made ...between smaller‐sooner and later‐larger rewards, (2) the Gambling Task (GT), in which choices are made between alternatives varying in pay‐off and punishment, and (3) the Rogers Decision‐Making Task (RDMT) in which subjects choose between higher or lower probability gambles. We examine the interrelationship among these tasks.
Design. A test battery was created which included the DDP, GT and RDMT, as well as measures of impulsivity, intellectual functioning and drug use.
Setting. Subjects completed the test battery at an outpatient center, prior to beginning 12 weeks of treatment.
Participants. Thirty‐two treatment‐seeking cocaine dependent individuals (primarily African‐American males) participated.
Findings. Performance on the GT was significantly correlated with performance on the DDP (
r = 0.37;
p = 0.04). Reaction times on the RDMT correlated with performance on the GT (
r = 0.36,
p = 0.04) and DDP (
r = 0.33,
p = 0.07), but actual choices on the RDMT did not (
p > 0.9 for both). While no significant relationships were observed between task performance and impulsivity, IQ estimate was positively correlated with both the GT (
r = 0.44,
p = 0.01) and RDMT (
r = 0.41,
p = 0.021). Split half reliability data indicated higher reliability when using only data from the latter half of the GT (
r = 0.92 vs.
r = 0.80).
Conclusions. These data offer preliminary evidence of overlap in the decision‐making functioning tapped by these tasks. Possible implications for drug‐taking behavior are discussed.
PDF
