Neuropsychological functioning in opioid use disorder: A research synthesis and meta-analysis

Background: Research has demonstrated that patients with opioid use disorders (OUD; including both opioid abuse and/or dependence) have poorer neuropsychological functioning compared to healthy controls; however, the pattern and robustness of the findings remain unknown.

Objectives: This study meta-analyzed the results from previous research examining the neuropsychological deficits associated with opioids across 14 neurocognitive domains.

Method: Articles comparing patients with OUD to healthy controls were selected based on detailed inclusion/exclusion criteria and variables of interest were coded. In total, 61 studies were selected for the analyses. These consisted of 2580 patients with OUD and 2102 healthy control participants (15.9% female). Drug-related variables were analyzed as potential moderators.

Results: The largest effect size difference in neuropsychological performance was observed in complex psychomotor ability. With the exception of the motor and processing speed domains, which showed no group differences, small-to-medium effect sizes were associated with all neurocognitive domains examined. Meta-regression revealed that increases in the length of abstinence were associated with decreases in effect sizes of the complex psychomotor domain. Additionally, attentional ability predicted effect size differences in executive functioning as well as verbal memory ability. Although the majority of meta-analyzed studies demonstrated significant differences between patients with OUD and controls, the average raw scores for patients with OUD in these studies typically fell within the normal range.

Conclusion: The pattern of neuropsychological performance among patients with OUD appears to reflect mild generalized cognitive dysfunction, with a large effect in complex psychomotor abilities.     

Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain

AIMS: To assess the relationship between methadone treatment (MT) and overdose and HIV/AIDS mortality among heroin users resident in Barcelona city. DESIGN: All patients who started treatment in any treatment centre between 1992 and 1997 were included in a cohort the first time they were admitted for heroin addiction treatment. Follow-up controls were carried out every 9 months, on average, until 31 December 1999. Variables, both constant and varying over time, were fitted into Cox regression models. FINDINGS: The study recruited 5049 patients, which provided 23,048.2 person-years. Fifty per cent were in MT during the study period; of the total cohort 1005 patients died: 38.4% due to AIDS, 34.7% to overdose and 27% to other causes. Overall mortality decreased from 5.9 deaths per 100 person-years in 1992 to 1.6 in 1999. Globally, life expectancy at birth was 39 years, 38 years lower than that of the general population. The main factor for overdose mortality was not being in MT at the time of death [relative ratio (RR) = 7.1]; other factors were being a current injector at baseline and being HIV positive. For AIDS mortality, the main factor was the calendar year (RR for 1996 versus 1999 = 4.6), the next major factor was more than 10 years of heroin consumption, followed by not being in MT, being unemployed, then having a prison record. CONCLUSIONS: The observed mortality decline could be linked to the effectiveness of low-threshold MT. The life expectancy of heroin users increased by 21 years during the study period.     

Genetic variants associated with addictive behavior in Colombian addicted and non-addicted to heroin or cocaine

Objective:

Determine the prevalence and compare some genetic markers involved in addictive behavior in a group of addicts to derivative of coca (cocaine/crack) or heroin and a control group of non-addicted people matched for gender, age and ethnicity.

Methods:

A 120 addicts and 120 non-addicts Colombian male were surveyed and genotyped for 18 polymorphism of the OPRM1, DRD2, DRD4, SLC6A3, SLC6A4, ABCB1, DβH and CYP2B6 genes. For the identification of alleles markers were used mini-sequencing and fragment multiplex PCR techniques; ethnicity of cases and controls was analyzed with 61 AIMs.

Results:

The age of onset use of heroin or coca derivatives (cocaine/crack) was 16.5±6 years and 99.2% of them consume several illicit drugs. It showed that controls and addicts belong to the same ethnic group. Significant differences between addicts and controls in relation to schooling, marital status, social security family history of substance abuse (p <0.001), Int8-VNTR SLC6A3 gene (p= 0.015) and SNP 3435C>T ABCB1 gene (p= 0.001) were found.

Conclusion:

The present results indicate that the VNTR- 6R polymorphism of the gene SLC6A3 and the genotype 3435CC in the ABCB1 gene, are both associated with addictive behavior to heroin or cocaine.     

UHPLC–MS/MS quantitation of porphyroxine in opium and application of porphyroxine‐acetylated products as signature markers for heroin

Porphyroxine, a trace alkaloid in opium, was identified in the early 1800s and isolated/characterized in the 1960s. Recently, two significant porphyroxine‐related byproducts found in the acidic and neutral extracts of illicit heroin were characterized by this laboratory as the N‐acetyl‐O¹⁴‐desmethyl‐epi‐porphyroxine ( B ) and N,O⁸‐diacetyl‐O¹⁴‐desmethyl‐epi‐porphyroxine ( C ). The prevalence of the B and C compounds has been consistent in the following order of abundance for the thousands of authentic heroin samples analyzed: Southwest Asia (SWA) > South America (SA) > Southeast Asia (SEA) > Mexico (MEX). In this research, a rapid and efficient ultra‐high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was developed to determine the content of porphyroxine and five primary alkaloids (morphine, codeine, thebaine, noscapine, and papaverine) in opium after extraction with methanol/water (50/50). The method was validated in terms of linearity, accuracy, recovery, and precision for porphyroxine. The limit of quantitation (LOQ) for porphyroxine was 2.5 ng/mL. The developed method was successfully applied to a total of 114 authentic opium samples from the major poppy‐growing regions. The amount of porphyroxine was determined at the level of part per thousand (‰) and the relative concentrations to morphine were in the range of 1x10^?4 and 1x10^?2 with an order of SWA > SEA, SA > MEX for its average abundance, which is consistent with the order of the average abundance of its acetylated products ( B , C ) in illicit heroin. This study reveals the significance of porphyroxine and its acylated compounds in classifying heroin and opium samples to major geographical regions of production.     

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Substance Use and Related Disorders. Part 2: Opioid dependence

Abstract

Objectives. To develop evidence-based practice guidelines for the pharmacological treatment of opioid abuse and dependence. Methods. An international task force of the World Federation of Societies of Biological Psychiatry (WFSBP) developed these practice guidelines after a systematic review of the available evidence pertaining to the treatment of opioid dependence. On the basis of the evidence, the Task Force reached a consensus on practice recommendations, which are intended to be clinically and scientifically meaningful for physicians who treat adults with opioid dependence. The data used to develop these guidelines were extracted primarily from national treatment guidelines for opioid use disorders, as well as from meta-analyses, reviews, and publications of randomized clinical trials on the efficacy of pharmacological and other biological treatments for these disorders. Publications were identified by searching the MEDLINE database and the Cochrane Library. The literature was evaluated with respect to the strength of evidence for efficacy, which was categorized into one of six levels (A–F). Results. There is an excellent evidence base supporting the efficacy of methadone and buprenorphine or the combination of buprenorphine and naloxone for the treatment of opioid withdrawal, with clonidine and lofexidine as secondary or adjunctive medications. Opioid maintenance with methadone and buprenorphine is the best-studied and most effective treatment for opioid dependence, with heroin and naltrexone as second-line medications. Conclusions. There is enough high quality data to formulate evidence-based guidelines for the treatment of opioid abuse and dependence. This task force report provides evidence for the efficacy of a number of medications to treat opioid abuse and dependence, particularly the opioid agonists methadone or buprenorphine. These medications have great relevance for clinical practice.     

Family Related Factors and Concurrent Heroin Use in Methadone Maintenance Treatment in China

Background: The use of heroin during Methadone Maintenance Treatment (MMT) is a challenging problem that contributes to poor treatment outcomes. Families may play an important role in addressing concurrent heroin use during MMT, especially in collectivist societies such as China. Objectives: In this study, we explored the relationship between family-related factors and concurrent heroin use during MMT in China. Methods: This study was conducted at 68 MMT clinics in five provinces of China. There were 2,446 MMT clients in the analysis. Demographic information, MMT dosage, family members' heroin use status, family support of MMT, family problem, and self-reported heroin use were collected in a cross-sectional survey. The most recent urinalysis of opiate use was obtained from clinical records. Results: Of the 2,446 participants, 533 (21.79%) self-reported heroin use in the previous seven days or had a positive urine morphine test result in the clinic record. Participants whose family member[s] used heroin were 1.59 times (95% CI: 1.17, 2.15) more likely to use concurrently during treatment. Those with family members who totally support them on the MMT were less likely to use (AOR: 0.75, 95% CI: 0.60, 0.94). Having more family problems was positively associated with concurrent heroin use (AOR: 2.01, 95% CI: 1.03, 3.93). Conclusions: The results highlight the importance of the family's role in concurrent heroin use during MMT programs. The study's findings may have implications for family-based interventions that address concurrent heroin use.     

In the absence of hard data,Is soft data better than no data at all?

Where total anonymity and confidentiality were previously respected in drug research, a tendency towards the provision of “hard” data such as verifiable personal details seriously disadvantages researchers working with “hidden groups” who use drugs in a relatively problem free way. This particularly applies to those who use substances generally regarded as highly addictive and problematic, such as heroin. Funding for a follow-up to an earlier research project was sought; the original investigated non-problematic heroin users, whereas the chief aim of the follow-up was to examine “resilience” to the problems commonly associated with the use of heroin. An illustration of attempting to put the gathering of “hard” verifiable data into action is presented here along with the immediate consequences. Unsurprisingly, the response of potential participants to the idea of providing personal details was largely negative, as the perceived consequences of being “outed” as a heroin user were generally regarded as worse than any of the issues associated with the use of the drug itself. An irony of the situation is that this “resilience” may be due to participant refusal to compromise their anonymity. This raises some obvious ethical issues. A number of potential longer term consequences on substance use/misuse research are also discussed.