Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers

Background: Drug addiction is associated with significant disease and death, but its impact on the ageing process has not been considered. The recent demonstration that many of the items available in routine clinical pathology have applicability as biomarkers of the ageing process implies that routine clinical laboratory parameters would be useful as an initial investigation of this possibility. Methods: 12,093 clinical laboratory results 1995-2006 were reviewed. To make the age ranges of the medical and addicted groups comparable the age range was restricted to 15-45 years. Results: 739 drug addicted (DA) and 5834 general medical (GM) age matched blood samples were compared. Significant elevation of immune parameters was noted in the C-reactive protein, erythrocyte sedimentation rate, total lymphocyte count, serum globulins and the globulin:albumin ratio (P < 0.01). Alanine aminotranferase, creatinine, urea, and insulin like growth factor-1 were also significantly higher (P < 0.01) in the DA group. Albumin, body mass index and dihydroepiandrosterone sulphate were unchanged and cholesterol was lower (all P < 0.05). Conclusion: These data demonstrate for the first time that addiction is associated with an altered profile of common biomarkers of ageing raising the possibility that the ageing process may be altered in this group. Infective and immune processes may be centrally involved. They suggest that addiction forms an interesting model to further examine the contribution of immune suppression and hyperstimulation to the ageing process

Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program

Background: There is on-going controversy in relation to the efficacy of naltrexone used for the treatment of heroin addiction, and the important covariates of that success. We were also interested to review our experience with two depot forms of implantable naltrexone. Methods: A retrospective review of patients' charts was undertaken, patients were recalled by telephone and by letter, and urine drug screen samples were collected. Opiate free success (OFS) was the parameter of interest. Three groups were defined. The first two were treated in the previous 12 months and comprised "implant" and "tablet" patients. A third group was "historical" comprising those treated orally in the preceding 12 months. Results: There were 102, 113 and 161 patients in each group respectively. Groups were matched for age, sex, and dose of heroin used, but not financial status or social support. The overall follow-up rate was 82%. The Kaplan Meier 12 month OFS were 82%, 58% and 52% respectively. 12 post-treatment variables were independently associated with treatment retention. In a Cox proportional hazard multivariate model social support, the number of detoxification episodes, post-treatment employment, the use of multiple implant episodes and spiritual belief were significantly related to OFS. Conclusion: Consistent with the voluminous international literature clinically useful retention rates can be achieved with naltrexone, which may be improved by implants and particularly serial implants, repeat detoxification, meticulous clinical follow-up, and social support. As depot formulations of naltrexone become increasingly available such results can guide their clinical deployment, improve treatment outcomes, and enlarge the policy options for an exciting non-addictive pharmacotherapy for opiate addiction

An intriguing association between dental and mental pathology in addicted and control subjects: A cross-sectional survey

Recent clinical studies suggest that substance use may be associated with an acceleration of the ageing process, possibly related to a deficit of stem cell number or function. As this clinic had access to both medical and drug dependent patients, we tested the hypothesis that there may be an association between previously identified deficits.A cross-sectional survey was performed looking at both dental and mental dysfunction. Both a dental index (DI) and a mental index (MI) were defined as previously described and utilised as summary measures of such pathology.From 249 substance use disorder (SUD) and 134 general medical controls (N-SUD), 248 and 91 patients were selected with ages less than 57 years as the primary focus of analysis. The mean (+/- S.D.) ages (32.59 +/- 7.98 vs 35.65 +/- 15.45 years) were similar. The DI was found to correlate with the MI in a significant manner in SUD (R = 0.14, p = 0.03), N-SUD (R = 0.27, p = 0.009) and in the whole group (R = 0.17, p = 0.001). The (univariate) association of MI with DI (p = 0.019) and DI with MI (p = 0.0037) remained highly significant at multivariate regression after adjustment for psychiatric diagnoses and measures of dose-duration exposure to common addictive drugs. The qualitative appearance of the surfaces of best fit for the relationship between age, DI and MI was different in the two groups.These results suggest that the robust statistical association between dental and mental pathology may be related to common underlying pathophysiological mechanisms such as a progeroid or stem cell deficiency process in clinical addiction