Long-term Heroin Use Research Articles

Exsanguination from ruptured femoral artery pseudoaneurysm - A fatal complication of groin heroin injection.

Intravenous drug users (IDUs) eventually encounter a common problem- a need to turn to a new vessel to inject drugs. Whether it is because no other spot is available due to scarring or convenience, the groin is the preferred spot for some. Chronic puncture of femoral vessels can lead to a rare but significant complication- femoral artery pseudoaneurysm (FAP). Its fatal consequence- rupture and bleeding is well recognized, but the forensic literature on this subject is limited. We present eight cases of exsanguination due to the ruptured FAP in IDUs who share most or all the following characteristics: long-term heroin use and/or pronounced drug use stigmata, chronic groin injection-related lesions, absence of significant precipitating pseudoaneurysm trauma, and no or minimal concentrations of heroin metabolites in blood. The FAP presentation varied greatly, from palpable fist-sized mass or slight elevation under the skin defect to infundibular arterio-cutaneous fistula that ruptured through the skin induration. In some, surrounding skin or soft tissue showed signs of inflammation but without suppuration. The most prominent FAP characteristic was smooth-surface cavitation on cross-sections. We performed microscopic evaluation in two cases and verified disruption of the artery wall (i.e., pseudoaneurysm) with elements of acute and chronic inflammation and fibrosis; foci of fibrinoid necrosis were noticed on the arterial wall. All subjects were pale, with faint hypostasis and organ anemia, consistent with reported massive hemorrhage. Because such sudden, unwitnessed, and suspicious deaths may raise the question of injury infliction, proper autopsy evaluation is crucial, for which we propose guidelines.

Several nAChRs gene variants are associated with phenotypes of heroin addiction in Chinese Han population

Heroin addiction is a chronic and complex brain disease. Nicotinic acetylcholine receptors (nAChRs) have been shown as major control points in many of the neurological and physiological disorders involved in heroin addiction. In the present study, thirty-three SNPs across nine nAChR genes were selected and probed for their associations with heroin addiction phenotypes in 801 unrelated northwestern Chinese Han patients. We found that rs2565055 in CHRNA2 gene was associated with daily dose of methadone treatment, and rs2672215, rs2672216 and rs2741865 in CHRNA10 gene were associated with the duration of the transition from first use to dependence (DTFUD). Cox multivariable regression analysis revealed that rs3743075, rs6495309 in CHRNA3, rs2304297 in CHRNA6, and rs1948 in CHRNB4 were associated with sexual desire in patients with heroin addiction. These findings were further supported by the identification of a haplotype block spanning CHRNA5, CHRNA3, and CHRNB4 that is correlated with changes in sexual desire after long-term heroin use. Our findings highlight associations between polymorphisms in nAChRs genes and the phenotypes of heroin addiction in the Chinese Han population. We suggest several nAChRs subunits as potential novel targets for the treatment of heroin addiction.

β-Arrestin 2 (ARRB2) Polymorphism is Associated With Adverse Consequences of Chronic Heroin Use.

β-arrestin 2 is an intracellular protein recruited during the activation of G-protein-coupled receptors. In preclinical studies, β-arrestin 2 has been implicated in µ-opioid receptor desensitization and internalization and the development of opioid tolerance and dependence. The present study investigated relationships between variants in the gene encoding β-arrestin 2 (ARRB2) and clinically relevant phenotypes among individuals with opioid use disorder (OUD). We hypothesized that ARRB2 variants would be associated with the negative effects of long-term heroin use. Chronic heroin users (N = 201; n = 103 African American; n = 98 Caucasian) were genotyped for ARRB2 r1045280 (synonymous, also affecting binding motif of transcription factor GTF2IRD1), rs2036657 (3'UTR) and rs3786047 (intron) and assessed for the past-month frequency of use, injection use, and lifetime duration of heroin use, number of heroin quit-attempts, and heroin use-related consequences. Lifetime heroin-use consequences (especially occupational and health-related) were significantly lower for African American ARRB2 r1045280 C-allele carriers compared withthe TT genotype. There was no significant genotype difference in the Caucasian group. ARRB2 rs2036657 was in strong linkage disequilibrium with rs1045280. These results, consistent with extant data, illustrate a role for ancestry-dependent allelic variation in ARRB2 r1045280 on heroin-use consequences. The ARRB2 r1045280 C-allele played a protective role in African-descent participants. These first-in-human findings, which should be replicated, provide support for mechanistic investigations of ARRB2 and related intracellular signaling molecules in OUD etiology, treatment, and relapse prevention. (Am J Addict 2021;00:00-00).

Long-term heroin use was associated with the downregulation of systemic platelets, BDNF, and TGF-β1, and it contributed to the disruption of executive function in Taiwanese Han Chinese

BackgroundLong-term heroin addicts have low plasma brain-derived neurotrophic factor (BDNF) levels. However, the mechanisms and effects of systemic disturbances of BDNF caused by heroin remain unclear. ObjectiveBlood platelet might be a source of neurotrophic factors like BDNF and transforming growth factor (TGF)-β1. Thus, we investigated the effects of heroin on platelets, BDNF and TGF-β1, the association between blood platelets, BDNF, TGF-β1, and executive function in long-term heroin addicts. MethodsWe enrolled 170 heroin addicts and 141 healthy controls. We measured their plasma BDNF and TGF-β1 levels and counted their platelets, red and white blood cells. The Wisconsin Card Sorting Test (WCST) was used to assess their executive function. ResultsPlasma BDNF and TGF-β1 levels were significantly downregulated in long-term heroin addicts. BDNF, TGF-β1, and platelet levels were lower in patients who had used heroin for more than 6 years than in those who had used it for less than 6 years. Lower plasma BDNF and TGF-β1 levels were highly correlated with the changes in platelet counts. In the WCST, the number of trials needed to complete the first category were negatively associated with platelet counts and BDNF levels. ConclusionsIn long-term heroin addicts, lower platelet counts contributed to lower plasma BDNF and TGF-β1 levels, which, in turn, contributed to the disruption of executive function after long-term heroin use. Neurotrophic- and platelet-protective agents might provide a useful research focus for heroin addiction therapy.

The Perceived Role of Family in Heroin Use Behaviors of Mexican–American Men

The influence of the family is not well understood as it relates to drug use behaviors of Hispanic male adults. We examined the family's influence on drug use behavior, as perceived by Hispanic men who use heroin. One-time qualitative interviews were conducted with 21 current and former heroin users who participated in a larger study on long-term heroin use in Mexican-American men. Data were analyzed using a thematic analysis approach. Three main themes emerged: family as a supportive environment for heroin use; heroin as a family legacy; and, the family's strategies for helping to stop using heroin. A sub-theme emerged on the paradox of family involvement, which spanned the three main themes. This research lays a foundation for future work to disentangle the risks and benefits of family involvement to inform culturally-centered therapies and cultural adaptations to traditional therapeutic approaches with Mexican-American men who abuse drugs.

Precocious transitions and long-term heroin use outcomes: A longitudinal study of gang-affiliated Mexican-American males

A longitudinal study (15years) investigates heroin use patterns following precocious transition experiences for gang-affiliated Mexican-American males (n=119) in San Antonio, Texas. Five precocious transitions are examined: cohabitation, early nest leaving, school dropout, teenage parenthood, and unemployment (while not in school). Half of these men used heroin over the follow-up period for an average of under 4years. Findings from a zero-inflated Poisson model indicate that while these transitions do not have a significant effect on initiation of heroin use, they do have an important influence on individual's drug trajectories once they have initiated. Early-nest leaving and teenage parenthood are protective factors for continued heroin use while dropping out of high school and cohabiting during this same period are risk factors. Findings are discussed within the context of these disadvantaged and marginalized communities.

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients.

BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p < 0.0001), but the distribution of the SNP was not significantly different. Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (<5 years) users. We conclude that plasma BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency.

Excessive suicide mortality and risk factors for suicide among patients with heroin dependence

BackgroundThe mortality risk is high among individuals dependent on heroin, and suicide is a severe consequence of long-term heroin use. We estimated the incidence of suicide mortality and its risk factors in a large Asian cohort with heroin dependence. MethodsA consecutive series of 2750 inpatients dependent on heroin admitted to a psychiatric center in northern Taiwan between 1990 and 2010 were retrospectively enrolled as the study cohort. These patients were linked to the Taiwan National Mortality Database to obtain each mortality event. We determined the Standardized Mortality Ratio (SMR) for each cause of death. Among the deceased, 69 deaths were due to suicide (cases); 138 controls were randomly selected using risk-set density sampling based on a nested case-control design. We collected clinical information from subjects’ medical records. Multivariate conditional logistic regression was employed to explore the correlates of suicide mortality. ResultsThe findings showed a 7.9-fold SMR for all-cause mortality among heroin users compared to the general population while the SMR for suicide mortality was 16.2. Multivariate analysis showed that suicide attempt as the reason for the index admission (adjusted risk ratio [RR]=4.29, p=0.035) and depressive syndrome anytime during life (adjusted RR=2.61, p=0.019) were associated with the risk of suicide mortality. ConclusionsIndividuals dependent on heroin are more likely to die of suicide compared to the general population. We recommend that clinical psychiatric staff carefully gather information related to the identified risk factors to prevent suicide among heroin users.

Effects of age, gender, duration of drug use and infection with viral hepatitis B and C on lymphocyte subsets in a population of HIV-negative injecting drug users in Italy.

A series of 716 HIV-negative IDUs entering a large drug treatment centre in central Italy was studied to evaluate the pattern of T-lymphocyte subsets among IDUs and to determine the effects of individual variables such as age, gender, duration of drug use and infection with viral hepatitis B and C. To this end, white cell count, total lymphocyte count and absolute number of lymphocyte subsets (i.e. CD3+, CD4+ and CD8+), HBV markers and HCV serology, were determined. For each individual, information on age, gender and duration of drug use was collected. To evaluate the association between level of lymphocyte subsets and phases of HBV infection, participants were stratified into three groups: (A) negative for all markers; (B) HBsAg-positive, with or without HBeAg, and HBsAb-negative; and (C) HBsAg and HBeAg-negative, positive for any other serological marker. The median absolute number of CD3+, CD4+ and CD8+ was 1909, 1080 and 770 cells/mm3, respectively, and did not vary across age bands. The CD8+ count was higher in males than in females. There was a tendency for CD3+ lymphocyte counts (mainly due to CD8+ counts) to be higher in individuals with 6-8 years of drug use compared to those who started injecting 4 years before or less. There was no evidence of increasing counts for a duration of drug use of more than 8 years. With regard to HBV, there was a general tendency for individuals in group "C" to have higher CD3+ and CD8+ counts than those in group "A". Finally, there was no difference in absolute lymphocyte count subsets between HCV-positive and HCV-negative IDUs. In conclusion, demographic and behavioural factors such as long-term heroin use or infection with HCV do not seem to influence the level of lymphocyte subsets among HIV-negative IDUs, nor does the infection with HBV seem to determine dramatic changes in CD4+ counts.

Methadone Use in Adolescent Heroin Addicts

Treating adolescent heroin addicts is a formidable task. The available evidence strongly suggests that the great majority do not achieve abstinence, but become even more heavily involved with drugs and crime. The present study suggests that treating these young addicts with methadone maintenance frequently stops or even reverses the socioeconomic decay associated with long-term heroin use.

Malaria in Drug Addicts

To the Editor.— We have recently observed eight cases of malaria due to the use of needles in common by heroin addicts. All eight were cases ofPlasmodium vivaxinfection. Three of these were related as man, wife, and sister; the other five have not admitted to a common pathway, but have acknowledged the use of heroin intravenously during a six-week period. All eight of these individuals gave a history of longterm heroin use, and all have complained of chills and fever of approximately four weeks' duration. Two of these patients were admitted as cases of fever of unknown orign (FUO), one to a psychiatric ward for observation, one as a patient with hepatitis, and four as known contacts. The patient with hepatitis and one of the patients with FUO demonstrated a positive Australia antigen by latex particle fixation. The other patients were negative for Australia antigen. Present studies are