Determination of thallium in urine, blood, and hair in illicit opioid users in Iran.

CONTEXT: Heavy metals, including thallium and lead, are introduced to illicit drug users' body as a result of using drugs such as cocaine and heroin. OBJECTIVE: This study aimed to determine urine, blood, and hair thallium (Tl) concentrations in illicit opioid users along with the relevant clinical signs and symptoms consistent with thallotoxicosis and to compare them with the corresponding variables in the control non-opioid user group. MATERIALS AND METHODS: This case-control study was conducted on 50 illicit opioid users who had abused opioids continuously for more than a year, referred to Amirie Drug Abuse Treatment Clinic in Kashan, Iran. The control group included 50 non-opioid users. Thallium concentrations in urine, blood, and hair were assessed in both groups (n = 100) using electrothermal (graphite furnace) atomic absorption spectrometry (ET AAS, GF AAS). RESULTS: In the studied group, the median (interquartile range) concentrations of thallium in urine, blood, and hair were 54.8 ± 79.9 µg/L, 14.5 ± 11.1 µg/L, and 5.4 ± 3.7 µg/g, respectively; these values were 4.8 ± 5.2 µg/L, 2.5 ± 2.4 µg/L, and 1.4 ± 1.1 µg/g, respectively, in the control group. There were significant differences in urine, blood, and hair thallium concentrations between the study group and the control group (p < 0.001). There were significant correlations between duration of illicit opioid use and urine thallium concentrations (r = 0.394, p = 0.005) and hair thallium concentrations (r = 0.293, p = 0.039), but not with blood thallium concentrations (r = 0.246, p = 0.085). Urine and blood thallium concentrations of illicit opioid users with clinical signs and symptoms consistent with thallotoxicosis of weakness (p = 0.01), depression (p = 0.03), and headache (p = 0.03) were higher than users without these problems. DISCUSSION AND CONCLUSION: The results of the study showed that thallium concentrations in urine, blood, and hair in illicit opioid users were significantly higher than the comparable concentrations in the control group. This can be due to the use of illicit opioids adulterated with thallium. Also, this study showed long-term illicit opioid use may lead to thallium exposure. In addition, cigarette smoking was associated with increased thallium exposure.

Clinical Aspects of Opium Adulterated with Lead in Iran: A Review.

Adulteration of drugs with poisonous substances during production or consumption has caused numerous health problems. Among contaminants that have the potential of producing poisonous effects are the heavy metals lead, arsenic and thallium that make up an important group of toxic substances. The emergence of these new health problems related to opioid abuse has precipitated this MiniReview on the status of the most hazardous and common opioid adulterants. In fact, adulterated opium is a major public health problem and can threaten the health of users. In this study, we searched for information on opium, opiates, lead poisoning, toxicity, intoxication, Iran and heavy metals in the TUMS Digital Library, PubMed, Scopus, EMBASE and Google Scholar bibliographical databases. This MiniReview primarily included articles on lead poisoning, signs and symptoms, and management in opioid-dependent individuals. Exclusion criteria were articles dealing with animal studies, specific paediatric studies, adulterants other than heavy metals and substances other than opioids. Adulterated opium is one of the new sources of exposure to lead and has precipitated an increase in lead-poisoned cases owing to the widespread use of opium. The toxicology of lead and general guidelines on diagnosis and treatment of lead poisoning is briefly reviewed. The symptoms of lead toxicity mimic several diseases often leading to unnecessary diagnostic methods, misdiagnoses and even surgery. Finally, owing to the fact that lead toxicity shows non-specific signs and symptoms, screening for this disease, by taking blood samples and assessing blood lead levels in high-risk people, should be given an utmost priority. It is recommended that screening tests are adopted and applied for any drug-abusing patient with non-specific subacute signs and symptoms like abdominal pain, constipation and anaemia.

Clinical trial of the effects of vitamin D supplementation on psychological symptoms and metabolic profiles in maintenance methadone treatment patients.

BACKGROUND: Vitamin D deficiency may be associated with some complications including nonspecific musculoskeletal pain and periodontal disease in maintenance methadone treatment (MMT) patients. This study was designed to determine the effect of vitamin D supplementation on psychological symptoms and metabolic profiles in MMT patients. METHODS: This randomized, double-blind, placebo-controlled, clinical trial was carried out among 68 MMT patients. Participants were randomly allocated to receive either 50,000IU vitamin D supplements (n=34) or placebo (n=34) every 2weeks for 12weeks. Fasting blood samples were taken at baseline and post-intervention to evaluate relevant variables. RESULTS: After the 12-week intervention, serum 25(OH) vitamin D levels significantly increased in the intervention group compared with the placebo group (+8.1±4.9 vs. -0.4±3.0, P<0.001). In addition, vitamin D supplementation significantly improved Pittsburgh Sleep Quality Index (-1.5±2.2 vs. -0.2±2.3, P=0.02) and Beck Depression Inventory (-4.8±7.3 vs. -1.5±6.1, P=0.04) compared with the placebo. Patients who received vitamin D supplements had significantly decreased fasting plasma glucose (-7.5±10.6 vs. +0.3±10.7mg/dL, P=0.004), serum insulin levels (-3.6±5.3 vs. -0.9±3.5 µIU/mL, P=0.01), homeostasis model of assessment-insulin resistance (-1.0±1.3 vs. -0.2±0.7, P=0.003), serum triglycerides (-9.6±30.8 vs. +15.6±30.2mg/dL, P=0.001), total- (-8.7±20.9 vs. +11.0±27.4mg/dL, P=0.001) and LDL-cholesterol (-11.1±17.9 vs. +5.9±27.5mg/dL, P=0.004) compared with the placebo. Additionally, vitamin D intake resulted in a significant decrease in serum high sensitivity C-reactive protein (-2.2±4.2 vs. +2.0±3.7mg/L, P<0.001), and significant increases plasma total antioxidant capacity (+26.2±99.8 vs. -86.3±127.5mmol/L, P<0.001) and glutathione levels (+292.3±172.4 vs. +48.9±208.9µmol/L, P<0.001) compared with the placebo. There was no significant effect of vitamin D supplementation on serum HDL-cholesterol, and other markers of insulin metabolism, inflammation and oxidative stress. CONCLUSIONS: Totally, taking 50,000IU vitamin D supplement every 2weeks for 12weeks in MMT patients had beneficial effects on psychological symptoms and few metabolic profiles.

[Changes and the impact on immune function of opioid-dependent subjects by Jitai tabelets during the withdrawal stage].

Objective: To detect the changes in the immune function of opioid-dependent subjects during the withdrawal stage through the administration of Jitai tablet. Methods: Subjects were treated as Jitai tablet alone, Jitai tablet plus buprenorphine and placebo, in a randomized,double-blind, placebo-controlled trial. Before and after the 14(th) day of withdrawal, levels of immunoglobulin (IgM, IgA, IgG), T cell subsets (CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+)) and cytokines (IL-2, IFN-γ, IL-4, IFN-γ/IL-4) were detected. Results: Compared with healthy people, immunity function before withdrawal among the opioid abusers showed higher levels of IgM, IL-2, IFN-γ, IL-4 and lower level of CD(3)(+)T, as (1.67±0.87) g/L, (14.44±13.50)%, (20.23±15.10)%, (1.97±1.59)%, (47.01±13.62)%, respectively, with difference statistically significant (P<0.05). There was no big difference of other immunity indicators between the two groups (P>0.05). At the 14(th) day of withdrawal in placebo group, levels of IL-4 returned to normal while IFN-γ/IL-4 ratio increased by 3.43 times (P<0.05). Levels of IgA, IgG, CD(4)(+) and CD(4)(+)/CD(8)(+) ratio fluctuated within normal range. There were no significant changes in other immunity indicators (P>0.05). Compared with placebo group, fluctuation of IgG and IgM decreased in Jitai group during withdrawal period, together with a normal level of IgM at the 14(th) day. Level of IL-4 abnormally rose up by 0.54 times in Jitai tablet plus buprenorphine group, while IFN-γ/IL-4 ratio been switched back at the 14(th) day of withdrawal. Other immune indicators were not affected by medical interventions. Conclusion: We noticed that certain impairment of the immune function might be restored by Jitai tablet during the withdrawal period.

Chronic lead poisoning in an Iranian opium smoker resident in London.

A 46-year-old man of Iranian origin presented with a 4-day history of colicky abdominal pain and absolute constipation on a background of several weeks of irritability and malaise. He had smoked 10 g of opium per week for a year and a half. On examination, he had diffuse abdominal tenderness and faecal loading. This was cleared, but the abdominal pain, nausea and vomiting persisted. He had extravascular haemolytic anaemia with punctate basophilic stippling on blood film. The patient's serum lead concentration was substantially elevated and he perhaps demonstrated Burton's line. The patient underwent chelation therapy and has recovered clinically and biochemically. Public health experts were notified and conducted an assessment of the risk to the patient and others; their lead exposure questionnaire was subsequently amended. This is an important case report of a UK resident describing lead toxicity secondary to the inhalation of opium.

The effect of opioid dependence on conventional and novel biochemical parameters of bone metabolism.

BACKGROUND: Opioids influence bone metabolism in several ways and osteoporosis associated with the long-term use of opioids is believed to be multifactorial. OBJECTIVES: To investigate the effect of opioid dependence on conventional and novel biochemical parameters of bone metabolism. To evaluate whether the concomitant HCV infection affects these parameters. METHODS: Fifty-nine opioid-dependent subjects and 23 healthy volunteers participated in the study. Parameters of bone metabolism were determined in serum. The determined parameters were procollagen type I N-terminal propeptide (PINP), serum Beta-Crosslaps Ι (ß-CTX), total calcium (Ca), inorganic phosphorus (P), parathormone (PTH) and alkaline phosphatase bone isoenzyme (ALP). RESULTS: The results of our study show that opioid-dependent subjects exhibit higher values in those biochemical markers that are indicative of increased osteoclast activity, such as ß-CTX and ALP, compared to healthy subjects. Furthermore, in opioid-dependent subjects the values of PTH were lower, while those of PINP were higher, in comparison to healthy individuals. No significant difference in the studied parameters was found when opioid-dependent subjects positive for anti-HCV antibodies were compared with opioid-dependent subjects negative for anti-HCV antibodies. CONCLUSION: Our findings show that there is increased bone turnover (bone metabolism) in opioid-dependent subjects, compared to healthy individuals. Future research on bone mineral density in these patients will help us evaluate whether the bone remodeling process is balanced or not.

Relationship between plasma concentrations of the l-enantiomer of methadone and response to methadone maintenance treatment.

This study evaluated the relationship between the plasma concentration of l-methadone and response to methadone in real-world patients, in order to identify a minimum plasma concentration above which methadone treatment is effective. Ninety-four patients with opioid dependence under maintenance methadone treatment were consecutively recruited. Response was defined as negative urine analyses in the three weeks prior to the blood sampling. The percentage of participants with a plasma l-methadone concentration between 100 and 250 ng/ml was 54.2% among those with a methadone dosage ≥60 mg/day. Plasma l-methadone concentrations were significantly higher in patients with negative urine analyses compared with those with positive urine analyses (median 93 vs. 77 ng/ml, Mann-Whitney test, P<0.05). Above plasma l-methadone concentrations of 200 ng/ml no heroin use was reported and urine analyses were negative. Moreover, above concentrations of 250 ng/ml craving was absent. Examination of demographic correlates of treatment outcome indicated that older age, a stable job and being married were protective against the use of heroin. Mean plasma l-methadone concentration was significantly lower in patients who used cannabis compared with those who did not use cannabis, after adjusting for methadone dosage. In conclusion our results identify specific cut-offs for plasma l-methadone concentrations about which therapeutic response is observed and provide new evidence that therapeutic response is associated with patient׳s demographic characteristics. This underscores the need to monitor plasma methadone concentrations as part of Drug Addiction Services routine practice, in order to provide an objective framework for changing the methadone dosage.

The plasma levels of the cytokines in opium-addicts and the effects of opium on the cytokines secretion by their lymphocytes.

The aim of this study was to evaluate the effects of opium addiction on the secretion of IL-4, IFN-γ, IL-6 and TGF-ß under in vivo and in vitro conditions. The blood samples were collected and PBMCs were cultured in RPMI1640 with and without opium for 48 h. The levels of the cytokines were measured using ELISA technique. The results showed that plasma levels of IL-4 and IFN-γ were significantly lower and IL-6 and TGF-ß were higher in plasma taken from opium-addicted subjects. The concentrations of all the cytokines in opium-addicted subjects in in vitro condition were significantly lower than the control group. Addicted subjects cultured lymphocytes significantly decrease secreted IL-4, IL-6 and TGF-ß but not IFN-γ in response to being cultured with opium, where as IFN-γ was increased in controls. These results may explain the frequent microbial infections and an increased tumor incidence seen in addicted patients.

Opium consumption is negatively associated with serum prostate-specific antigen (PSA), free PSA, and percentage of free PSA levels.

Addiction to opium continues to be a major worldwide medical and social problem. The study addressing the association between opium consumption and serum prostate-specific antigen (PSA) level is lacking. We determined the effects of opium consumption on serum PSA levels in opium-addict men. Our study subjects comprised 438 opium-addict men with a mean age of 52.2 ± 6.4 years (group 1). We compared these men with 446 men who did not indicate current or past opium use (group 2). Serum total PSA (tPSA), free PSA (fPSA), % fPSA, and sex hormones were compared between the 2 groups. The mean serum tPSA level was significantly lower in group 1 (1.05 ng/mL) than in controls (1.45 ng/mL) (P = 0.001). Opium consumption was also associated with lower fPSA (P = 0.001) and % fPSA (P = 0.001). Serum free testosterone level in opium-addict patients (132.5 ± 42 pg/mL) was significantly lower than that in controls (156.2 ± 43 pg/mL) (P = 0.03). However, no significant correlation existed between tPSA and free testosterone levels (r = 0.28, 95% CI, -0.036 to 0.51, P = 0.34). Among the patients with cancer in group 1, 35% were found to have high-grade tumor (Gleason score ≥ 7) compared with 26.7% in group 2 (P = 0.02). Total PSA and fPSA were strongly correlated with duration of opium use (r = -0.06, 95% CI, -0.04 to -0.08, P = 0.0001; and r = -0.05, 95% CI, -0.03 to -0.07, P = 0.0001, respectively). Opium consumption is independently and negatively associated with serum tPSA, fPSA, and % fPSA levels.

Opium addiction increases interleukin 1 receptor antagonist (IL-1Ra) in the coronary artery disease patients.

BACKGROUND: There is evidence that opium addiction has immunosuppressant effects. Coronary artery disease (CAD) is a condition resulted from atherosclerosis which is dependent on the immune response. PURPOSE: To evaluate plasma levels of interleukin-6 and interleukin-1Ra in 30 patients with three-vessel coronary artery disease, ejection fraction of more than 35% and to evaluate their changes after prognostic treadmill test in 15 opium addicted and 15 non-addicted patients. METHODS: The participants underwent prognostic treadmill test and plasma levels of interleukin-6 (IL-6) and interleukin-1Ra (IL-1Ra) were evaluated with ELISA method before, just after and 4 hours after the test. RESULTS: IL-1Ra (2183 pg/ml) tended to decrease over time in the opium addicted group (1372 pg/ml after prognostic treadmill test and 1034 pg/ml 4 hours after that), although such decrease did not reach the statistical significance. IL-1Ra levels were significantly higher in opium addicted than in non addicted patients. Opium addiction had no significant effect on IL-6 changes. CONCLUSION: Consumption of opium in CAD patients is associated with higher IL-1Ra levels.

Oral opium: an unusual cause of lead poisoning.

INTRODUCTION: The number of cases of lead poisoning (LP), a widely known disease with various aetiologies, being reported globally has decreased over the years due to both limited domestic applications of lead and enforcement of stringent safety measures. However, a new presentation of lead poisoning, lead-contaminated opium (LCO), is gradually emerging in our region. This study aimed to determine the prevalence and clinical effects of lead toxicity associated with opium use. METHODS: Between November 2006 and December 2007, all patients diagnosed with LP at a central laboratory in Tehran, Iran, were assessed for potential causes of poisoning. Patients with a history of LCO abuse were evaluated and recruited for the study. RESULTS: Overall, there were 240 patients with LP, and poisoning from LCO was diagnosed in 25 patients. The duration of addiction was between three months and 40 years, and the duration of symptoms was 28.1 ± 17.7 days. Mean blood lead levels of the patients were 145 ± 61 (range 61-323) µg/dL. The average creatinine and haemoglobin levels were 77.4 ± 8.1 µmol/L and 105 ± 25 g/L, respectively. The association between the duration of addiction and levels of lead in blood was not statistically significant (r = -0.142, p = 0.54). The most common symptoms were gastrointestinal complaints, followed by musculoskeletal complaints with muscle weakness (92%). Anorexia was also a leading complaint. CONCLUSION: The results of our study suggest that the possibility of LP should be considered with high suspicion among opium users presenting with acute abdominal symptoms.

Impact of opium on the serum levels of TGF-ß in diabetic, addicted and addicted-diabetic rats.

BACKGROUND: Several cells of immune system such as regulatory T cells and macrophages secrete transforming growth factor-ß (TGF-ß) in response to different stimuli. This cytokine has inhibitory effect on immune system and diminished production of this cytokine is associated with autoimmune disorders. OBJECTIVE: The aim of this study was to evaluate the influence of opium addiction on serum level of TGF-ß in male and female diabetic and non-diabetic Wistar rats. METHODS: This experimental study was performed on normal, opium addicted, diabetic and addicted-diabetic male and female rats. Serum level of TGF-ß was measured by ELISA. RESULTS: The results of our study indicated that the mean serum level of TGF-ß in female addicted rats was significantly increased compared to control group (p<0.004). Conversely, in male addicted rats the mean serum level of TGF-ß was lower compared with control (p<0.065). CONCLUSION: Our results suggest that opium and its derivatives have differential inductive effects on the cytokine expression in male and female rats.

Comparison of serum lead level in oral opium addicts with healthy control group.

BACKGROUND: Drug abuse and its consequences are major health problems in Middle-East countries such as Iran. Salesmen and smugglers may add lead to opium during the process of opium preparation to increase the weight of opium for more profit. Several reports have found lead poisoning symptoms in opium addicted patients and there are many nonspecific symptoms mimicking lead poisoning in opium addicted patients. As far as the literature review is concerned, there is no comparative study about blood lead level (BLL) in addicted patients with healthy controls. Therefore, it seems evaluation of blood lead level in opium addicted patients to be important. METHODS: In this study, the BLL of forty-four subjects in two patient and control groups was evaluated. The patient group (22 subjects) was comprised of patients who used oral opium. Control group (22 subjects) was matched with the patient group for age and sex, considering inclusion and exclusion criteria with a mean age of 38.8+/-6.7. For blood lead assay, 3 mL of whole blood was obtained from both groups by venipuncture and BLL was assessed immediately using an atomic absorption spectrophotometer. RESULTS: The BLL in patient group had a range of 7.2 to 69.9 g/dL with a mean of 21.9+/-13.2. In the healthy control group, BLL was between 4.1 to 17.4 g/dL with a mean of 8.6+/-3.5. The mean difference of both groups (t=4.56) was statistically significant (P<0.0001). In the patient group, BLL had a significant correlation with the amount of opium ingested (r=0.65, P<0.01). However, there was no significant correlation with duration of opium ingestion in the patient group. CONCLUSION: It would be concluded that opium addicts have an elevated BLL compared to healthy controls. Therefore, screening of blood lead concentration is helpful for opium addicted people especially with non-specific symptoms. In this regard, a similar investigation with a larger sample size of opium addicted patients (including both oral and inhaled) and a control group is suggested to confirm the findings of this research.

Effect of opium addiction on lipid profile and atherosclerosis formation in hypercholesterolemic rabbits.

In some Asian and Middle Eastern societies, opium consumption has traditionally been regarded as a way to lower blood lipids and to prevent heart diseases. This could eventually lead to addiction. In this study, the effect of oral opium consumption on serum lipids and atherogenesis in rabbits was investigated. Twenty-eight male New Zealand white rabbits were divided into control, hypercholesterolemic, addicted, and hypercholesterolemic-addicted groups and were studied for 3 months. Serum lipid profile was determined at the beginning of the study and at 1 month intervals thereafter. At the end of the study period, aortic plaque formation was assessed. Compared with control, in the hypercholesterolemic and hypercholesterolemic-addicted groups, cholesterol, triglycerides, and low-density lipoprotein cholesterol levels were significantly increased (P<0.01). The increases in lipids and lesion areas in the aorta were higher in hypercholesterolemic-addicted than hypercholesterolemic group (P<0.05). Our findings suggest that opium consumption can have aggravating effects in atherosclerosis formation related with hypercholesterolemia, mainly affecting lipid profile.

Abdominal pain due to lead-contaminated opium: a new source of inorganic lead poisoning in Iran.

Although the incidence of occupational and adult lead poisoning has declined, the problem still exists. We encountered three patients with lead poisoning in Iran, all of whom associated with presented with diffuse abdominal pain, which was at times colicky in nature, anemia, constipation, nausea, vomiting, and slightly abnormal liver biochemistries. A history of opium ingestion was present in each of these patients. None of the patients reported known occupational exposure to toxins. Diagnoses of lead poisoning were confirmed through the detection of elevated blood lead levels. The cause of lead poisoning was attributed to the ingestion of contaminated opium. Opium adulterated with lead had not been previously recognized as a source of lead poisoning in Iran. It is, therefore, pointed out that lead poisoning should be considered as a differential diagnosis for acute abdominal colic of unclear cause in patients with opium addiction.

Enhanced prolactin levels in opium smokers.

In Iran, opium is smoked for pleasure or as a medication by some people. It is a complex mixture of 40 different alkaloids, including morphine and codeine along with many impurities. Although it is well established that opioids or tobacco affect many physiological functions in humans, to our knowledge there has been no specific study looking at these effects in opium smokers. To assess that, we investigated the circulating levels of prolactin, TSH, LH, FSH and testosterone in male opium smokers who also smoke cigarettes (n=23, aged 28.4+/- 4.1 years), and comparing this with the corresponding values for nicotine abusers (n=12, 15-25 cigarettes/day) or a healthy control group (n=20) of the same age. Our results showed that 86.96% of the opium-dependent and 41.67 % of the nicotine-dependent group displayed high prolactin values (p<0.002). In addition, there was a positive correlation between the dose of opium and the plasma prolactin level of opium dependents (p=0.748, p<0.001). Low FSH was detected in 43.48% of the opium smokers and 50% of the cigarette smokers (p<0.001) with normal LH and testosterone levels. TSH of the opium smokers was also lower than that of the other two groups (p<0.002). In conclusion, the present data indicate that chronic opium and cigarette smoking may synergistically influence pituitary hormone production through the effects on neuropeptides produced either locally or systemic.

Comparison of tincture of opium and methadone to control opioid withdrawal in a Thai treatment centre.

AIMS: To evaluate the effectiveness of oral tincture of opium (TOP) and methadone to control opioid withdrawal in patients in northern Thailand. METHODS: Open label, parallel group study in an inpatient facility compared 15 former heroin users receiving methadone 5-20 mg 12 hourly with 15 former opium smokers receiving TOP (3.33-10 mg morphine equivalents 12 hourly). At 0, 1, 3 and 8 h, blood, withdrawal scores and subjective opioid effects were collected. RESULTS: There was a reciprocal association between withdrawal scores/direct subjective opioid effects and plasma (R)-methadone, but not plasma morphine, concentrations. Withdrawal scores at the time of dosing were higher in the TOP patients (9.1 +/- 3) than in the methadone patients (4.5 +/- 4.6) and in the TOP patients were significantly (P = 0.001) attenuated at 3 and 8 h. CONCLUSIONS: At the doses used, TOP was inferior to methadone in suppressing withdrawal. It could prove to be a cost effective and valuable drug, but only after dose size and frequency are further investigated.

Effects of opium addiction on some serum factors in addicts with non-insulin-dependent diabetes mellitus.

The aim of this study was to determine the effect of opium on biochemical parameters in addicts with non-insulin-dependent diabetes mellitus (NIDDM). Twenty-three males and 26 females between 35 and 65 years of age, with NIDDM, addicted to opium, were selected as the case group. Twenty-three males and 26 females with NIDDM and no opium addiction served as controls. Fasting glucose, glycated haemoglobin (HbA1c), total cholesterol, high density lipoproteins-cholesterol (HDL-c), triglycerides (TGs), sodium (Na(+)), potassium (K(+)), calcium (Ca(2+)), iron (Fe(2+)), total iron binding capacity (TIBC), serum total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid and urea were measured in the serum of the two groups. Serum protein electrophoresis was also carried out. Compared to the control group, in addicted males with NIDDM, HbA1c, K(+) and Fe(2+) were higher, and serum total protein, ALT and HDL-c were lower. No significant difference was observed between other factors. Albumin was lower in addicts, but no significant difference was observed between the albumin/globulin ratios. In addicted females with NIDDM, serum total protein, TIBC, ALT and AST were lower compared to non-addicts. Cholesterol tends to be lower in diabetic addicted males, HbA1c in addicted females and uric acid in addicted males was higher compared to non-addicted diabetics. Their differences, however, were not significant. According to our results, smoking opium increases serum glucose and decreases HDL-c, and thus adds to metabolic disorders in NIDDM patients. It also increases potassium and Fe(2) in males and decreases TIBC in females, and could therefore potentially interfere with water and iron metabolism.

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.