Plasma metabolites changes in male heroin addicts during acute and protracted withdrawal.

BACKGROUND: Heroin addiction and withdrawal have been associated with an increased risk for infectious diseases and psychological complications. However, the changes of metabolites in heroin addicts during withdrawal remain largely unknown. METHODS: A total of 50 participants including 20 heroin addicts with acute abstinence stage, 15 with protracted abstinence stage and 15 healthy controls, were recruited. We performed metabolic profiling of plasma samples based on ultraperformance liquid chromatography coupled to tandem mass spectrometry to explore the potential biomarkers and mechanisms of heroin withdrawal. RESULTS: Among the metabolites analyzed, omega-6 polyunsaturated fatty acids (linoleic acid, dihomo-gamma-linolenic acid, arachidonic acid, n-6 docosapentaenoic acid), omega-3 polyunsaturated fatty acids (docosahexaenoic acid, docosapentaenoic acid), aromatic amino acids (phenylalanine, tyrosine, tryptophan), and intermediates of the tricarboxylic acid cycle (oxoglutaric acid, isocitric acid) were significantly reduced during acute heroin withdrawal. Although majority of the metabolite changes could recover after months of withdrawal, the levels of alpha-aminobutyric acid, alloisoleucine, ketoleucine, and oxalic acid do not recover. CONCLUSIONS: In conclusion, the plasma metabolites undergo tremendous changes during heroin withdrawal. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and withdrawal stages in heroin addicts.

Time course of microglia activation and brain and blood cytokine/chemokine levels following chronic ethanol exposure and protracted withdrawal in rats.

Alcohol produces complex effects on the immune system. Moderate alcohol use (1-2 drinks per day) has been shown to produce anti-inflammatory responses in human blood monocytes, whereas, the post mortem brains of severe alcoholics show increased immune gene expression and activated microglial markers. The present study was conducted to evaluate the time course of alcohol effects during exposure and after withdrawal, and to determine the relationship between microglial and cytokine responses in brain and blood. Forty-eight adult, male Wistar rats were exposed to chronic ethanol vapors, or air control, for 5 weeks. Following ethanol/air exposure blood and brains were collected at three time points: 1) while intoxicated, following 35 days of air/vapor exposure; 2) following 24 h of withdrawal from exposure, and 3) 28 days after withdrawal. One hemisphere of the brain was flash-frozen for cytokine analysis, and the other was fixed for immunohistochemical analysis. The ionized calcium-binding adapter molecule 1 (Iba-1) was used to evaluate microglia activation at the three time points, and rat cytokine/chemokine Magnetic Bead Panels (Millipore) were used to analyze frontal cortex tissue lysate and serum. Ethanol induced a significant increase in Iba-1 that peaked at day 35, remained significant after 1 day of withdrawal, and was elevated at day 28 in frontal cortex, amygdala, and substantia nigra. Ethanol exposure was associated with a transient reduction of the serum level of the major pro- and anti-inflammatory cytokines and chemokines and a transient increase of effectors of sterile inflammation. Little or no changes in these molecules were seen in the frontal cortex except for HMG1 and fractalkine that were reduced and elevated, respectively, at day 28 following withdrawal. These data show that ethanol exposure produces robust microglial activation; however, measures of inflammation in the blood differ from those in the brain over a protracted time course.

Safety and tolerability of sauna detoxification for the protracted withdrawal symptoms of substance abuse.

OBJECTIVE: Protracted drug withdrawal symptoms can last months or years after drug cessation, often precipitating a return to substance misuse. We evaluated the safety and preliminary health benefits of a unique chemical exposure regimen based on exercise, sauna and therapeutic nutrients. METHODS: This was a prospective evaluation of 109 individuals sequentially enrolled into a sauna detoxification component of a multi-modal, long-term residential substance abuse treatment centre. RESULTS: Data from medical charts, client self-reports and Short Form Health Survey (SF-36) responses indicated that the Hubbard sauna detoxification method was well tolerated, with a 99% completion rate, including one human immunodeficiency virus and nine hepatitis C positive clients. There were no cases of dehydration, overhydration or heat illness. Statistically significant improvements were seen in both mental and physical SF-36 scores at regimen completion, as well as in Addiction Severity Index and Global Appraisal of Individual Needs Short Screener change scores at rehabilitation program discharge, compared with enrolment. CONCLUSIONS: The regimen lacked serious adverse events, had a very low discontinuation rate and high client-reported satisfaction. The SF-36 data indicated improved physical and emotional symptoms. Therefore, broader investigation of this sauna-based treatment regimen is warranted.

Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving.

BACKGROUND: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. METHODS: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. RESULTS: The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. CONCLUSIONS: Findings demonstrate that broad immunosuppression is still observed in alcohol-dependent individuals after 3 weeks of abstinence and may be linked to motivation for alcohol.

[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.

Mindfulness and pharmacological prophylaxis have comparable effect on biomarkers of inflammation and clinical indexes in chronic migraine with medication overuse: results at 12 months after withdrawal.

Chronic migraine (CM) is a disabling condition arising from a complex mixture of interconnected biological, psychological and social factors, and is often associated with medication overuse (MO). Mindfulness is emerging as a helpful treatment for pain, and one study showed that the longitudinal 12 months' course of CM-MO patients that attended mindfulness-based treatment alone was similar to that of patients receiving medical prophylaxis alone; in this study, we describe the course of biomarkers of inflammation. Our results provide initial evidence of sustained similar effects on reduced concentration of biomarkers of inflammation, although not sizeable enough to reach statistical significance. Whether more intensive treatment and/or larger samples would lead to greater changes is unknown, but these encouraging preliminary findings suggest further research is warranted.

Effects of acupuncture at Zu-San-Li (ST36) on the activity of the hypothalamic--pituitary--adrenal axis during ethanol withdrawal in rats.

The current study investigated the effects of acupuncture at Zu-San-Li (ST36) on the hypothalamic-pituitary-adrenal axis during ethanol withdrawal in rats. Rats were intraperitoneally treated with 3 g/kg/day of ethanol or saline for 28 days. Following 24 hours of ethanol withdrawal, acupuncture was applied at bilateral ST36 points or non-acupoints (tail) for 1 minute. Plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay (RIA), and the corticotropin-releasing factor (CRF) protein levels in the paraventricular nucleus of the hypothalamus were also examined by RIA 20 minutes after the acupuncture treatment. RIA showed significantly increased plasma levels of CORT and ACTH in the ethanol-withdrawn rats compared with the saline-treated rats, which were inhibited significantly by the acupuncture at the acupoint ST36 but not at the non-acupoint. Additionally, ethanol withdrawal promoted CRF protein expressions in the paraventricular nucleus of the hypothalamus, which were also blocked by the acupuncture at ST36. These findings suggest that acupuncture at the specific acupoint ST36 can inhibit ethanol withdrawal-induced hyperactivation of hypothalamic-pituitary-adrenal axis, and it may be mediated via the modulation of hypothalamic CRF.

Effects of Jitai tablet, a traditional Chinese medicine, on plasma adrenocorticotropic hormone and cortisol levels in heroin addicts during abstinence.

OBJECTIVES: To investigate the changes in adrenocorticotropic hormone (ACTH) and cortisol in heroin addicts given Jitai tablet treatment during abstinence. DESIGN: Double-blind, randomized, placebo-controlled clinical trial. SETTINGS/LOCATION: Drug Rehabilitation Bureau of Shanghai Police, China. PARTICIPANTS: 99 volunteers, including 69 heroin addicts and 30 healthy volunteers. INTERVENTIONS: 69 heroin addicts randomly divided into two groups: the Jitai tablet group, which comprised 34 heroin addicts given Jitai tablet treatment during abstinence, and the placebo group, which comprised 35 heroin addicts given placebo. A control group consisted of 30 sex- and age-matched healthy volunteers. OUTCOME MEASURES: ACTH and cortisol in plasma were measured in all groups at baseline and in the Jitai tablet and placebo groups on the third, seventh, and 14th days of abstinence. RESULTS: Levels of both ACTH (p<.01) and cortisol (p<.001) were significantly higher in heroin addicts at baseline than in the healthy volunteers. Jitai tablet treatment restored plasma cortisol levels to normal more rapidly than did placebo treatment (p<.05), but not ACTH levels. A positive correlation between ACTH and cortisol values at baseline (p<.01) was also found with withdrawal symptom scores and daily dosages of heroin. CONCLUSIONS: Heroin addicts could respond to Jitai tablets through changes in the hypothalamus-pituitary-adrenal axis.

Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.

BACKGROUND: Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge. METHODS: Eleven daily cannabis smokers received 0, 30, 60, or 120 mg/d THC for four 5-day medication sessions, each separated by 9 days of ad libitum cannabis smoking. On the fifth day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the first and fifth days was quantified by two-dimensional gas chromatography mass spectrometer for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5-100 for THC, 1-50 for 11-OH-THC, and 0.5-200 for THCCOOH. RESULTS: During placebo dosing, THC, 11-OH-THC, and THCCOOH concentrations consistently decreased, whereas all cannabinoids increased dose dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during the 60- and 120-mg/d doses, and THCCOOH increased significantly only during the 120-mg/d dose. THC, 11-OH-THC, and THCCOOH concentrations peaked within 0.25 hours after cannabis smoking, except after 120 mg/d THC when THCCOOH peaked 0.5 hours before smoking. CONCLUSIONS: The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake.

Influence of environmental enrichment on hypothalamic-pituitary-adrenal (HPA) responses to single-dose nicotine, continuous nicotine by osmotic mini-pumps, and nicotine withdrawal by mecamylamine in male and female rats.

In the present study, we determined the effects of environmental enrichment (EE; Kong Toys and Nestlets) on sexually diergic HPA axis responses to single-dose nicotine (NIC), single-dose NIC following continuous NIC administration for two weeks, and NIC withdrawal by single-dose mecamylamine (MEC) in male and female rats. Blood sampling occurred before and after MEC and NIC administrations for the determination of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Supporting and extending our previous findings, EE appeared to produce anxiolytic effects by reducing hormone responses: Male and female rats housed with EE had lower baseline ACTH and significantly lower HPA axis responses to the mild stress of saline (SAL) injection than did those housed without EE. The sexually diergic responses to single dose NIC, continuous NIC, and MEC-induced NIC withdrawal were reduced by EE in many male and female groups. ACTH responses to continuous NIC and MEC-induced NIC withdrawal were blunted to a greater extent in female EE groups than in male EE groups, suggesting that females are more sensitive to the anxiolytic effects of EE. Because EE lowered stress-responsive hormones of the HPA axis in most groups, EE may be a useful intervention for stress reduction in animal models of NIC addiction. As well, the effectiveness of EE in animal studies of NIC withdrawal may enlighten human studies addressing coping styles and tobacco cessation in men and women.

Decreased galanin serum levels are associated with alcohol-craving during withdrawal.

BACKGROUND: The hypothalamic galanin expression has been associated with increased intake of carbohydrates and fats in preclinical studies. The appetite stimulating effect of galanin is thought to underlie the positive association between alcohol consumption and hypothalamic galanin expression observed in preclinical studies. METHODS: In this pilot study we investigated alterations in galanin serum levels (33 male patients) in alcohol-dependent patients during alcohol withdrawal (days 1, 7 and 14) in comparison to healthy controls (19 male controls). In order to assess the putative association between appetite regulation, galanin serum levels and alcohol consumption we additionally investigated the serum levels of insulin, glucose and triglycerides. RESULTS: The galanin serum levels on day 1 of alcohol withdrawal were significantly reduced in the alcohol-dependent patients (T=-3.302, p=0.002) and increased significantly from day 1 to day 14 of alcohol withdrawal (F=6.437, p=0.002). We found a significant negative association between the galanin serum levels and alcohol craving measured by the Obsessive Compulsive Drinking Scale (OCDS) (r=-0.449, p=0.009) and the obsessive subscale of the OCDS (r=-0.521, p=0.002) on day 1 of alcohol withdrawal. There was no association between the galanin serum levels and the parameters of energy homeostasis (triglycerides, cholesterol, insulin, and glucose) investigated. CONCLUSIONS: Acute alcohol withdrawal was associated with decreased galanin serum levels in this pilot study. There was no association between the galanin serum levels and the parameters of energy homeostasis. Further research of galanin serum levels in active drinkers will be necessary to clarify the putative association between galanin serum levels, appetite regulation and alcohol consumption.

Impaired emotional-like behavior and serotonergic function during protracted abstinence from chronic morphine.

BACKGROUND: Opiate abuse is a chronic relapsing disorder, and maintaining prolonged abstinence remains a major challenge. Protracted abstinence is characterized by lowered mood, and clinical studies show elevated comorbidity between addiction and depressive disorders. At present, their relationship remains unclear and has been little studied in animal models. Here we investigated emotional alterations during protracted abstinence, in mice with a history of chronic morphine exposure. METHODS: C57BL6J mice were exposed to a chronic intermittent escalating morphine regimen (20-100 mg/kg). Physical dependence (naloxone-precipitated withdrawal), despair-related behaviors (tail suspension test), and social behaviors were examined after 1 or 4 weeks of abstinence. Stress hormones and forebrain bioamine levels were analyzed at the end of morphine regimen and after 4 weeks of abstinence. Finally, we examined the effects of chronic fluoxetine during abstinence on morphine-induced behavioral deficits. RESULTS: Acute naloxone-induced withdrawal was clearly measurable after 1 week, and became undetectable after 4 weeks. In contrast, social and despair-related behaviors were unchanged after 1 week, but low sociability and despair-like behavior became significant after 4 weeks. Chronic morphine regimen increased both corticosterone levels and forebrain serotonin turnover, but only serotonergic activity in the dorsal raphe remained impaired after 4 weeks. Remarkably, chronic fluoxetine prevented depressive-like behavioral deficits in 4-week abstinent mice. CONCLUSIONS: During protracted abstinence, the immediate consequences of morphine exposure attenuate, whereas fluoxetine-sensitive emotional alterations strengthen with time. Our study establishes a direct link between morphine abstinence and depressive-like symptoms and strongly suggests that serotonin dysfunction represents a main mechanism contributing to mood disorders in opiate abstinence.

An endocannabinoid signal associated with desire for alcohol is suppressed in recently abstinent alcoholics.

BACKGROUND: Alcoholics report persistent alcohol craving that is heightened by cognitive cues, stressful situations, and abstinence. The role of endogenous cannabinoids in human alcohol craving--though long suspected--remains elusive. MATERIALS AND METHODS: We employed laboratory exposure to stress, alcohol cue, and neutral relaxed situations through guided imagery procedures to evoke alcohol desire and craving in healthy social drinkers (n = 11) and in treatment-engaged, recently abstinent alcoholic subjects (n = 12) and assessed alcohol craving, heart rate, and changes in circulating endocannabinoid levels. Subjective anxiety was also measured as a manipulation check for the procedures. RESULTS: In healthy social drinkers, alcohol cue imagery increased circulating levels of the endocannabinoid anandamide, whereas neutral and stress-related imagery had no such effect. Notably, baseline and response anandamide levels in these subjects were negatively and positively correlated with self-reported alcohol craving scores, respectively. Cue-induced increases in heart rate were also correlated with anandamide responses. By contrast, no imagery-induced anandamide mobilization was observed in alcoholics, whose baseline anandamide levels were markedly reduced compared to healthy drinkers and were uncorrelated to either alcohol craving or heart rate. CONCLUSIONS: The results suggest that plasma anandamide levels provide a marker of the desire for alcohol in social drinkers, which is suppressed in recently abstinent alcoholics.

Compartmental analysis of plasma and liver n-3 essential fatty acids in alcohol-dependent men during withdrawal.

The mechanism by which chronic ethanol consumption reduces concentrations of long chain polyunsaturated (LCP) fatty acids (FA) in tissues of humans was investigated in alcohol-dependent (AD) men during early withdrawal and to a well-matched control group by fitting the concentration-time curves of d(5)-labeled n-3 FA from plasma and liver, which originated from an oral dose of d(5)-linolenic acid (d(5)-18:3n-3) ethyl ester to a compartmental model. Blood sampled over 168 h and a liver specimen obtained 96 h after isotope administration were analyzed for d(5)-18:3n-3, d(5)-20:5n-3, d(5)-22:5n-3, and d(5)-22:6n-3. Plasma 20:5n-3 and 22:5n-3 were lower in AD subjects, compared with controls (20:5n-3: -50%, 22:5n-3: -34%). Increased amounts of d(5)-18:3n-3 were directed toward synthesis of d(5)-20:5n-3 in AD subjects (P < .05). However, this effect was offset by larger amounts of 20:5n-3 lost from plasma (control: 2.0 vs. AD: 4.2 mg d(-1)). In livers of AD subjects, more d(5)-18:3n-3 and d(5)-22:5n-3 were utilized for synthesis of d(5)-20:5n-3 (+200%) and d(5)-22:6n-3 (+210%), respectively, than was predicted from plasma kinetics. Although, the potential to utilize linolenic acid for synthesis of LCP FA was greater in AD subjects compared with controls, heightened disappearance rates of 20:5n-3 reduced overall plasma concentrations of several endogenous n-3 LCP FA.

Effects of withdrawal of Xuezhikang, an extract of cholestin, on lipid profile and C-reactive protein: a short-term time course study in patients with coronary artery disease.

OBJECTIVE: C-reactive protein (CRP) is considered a risk factor for coronary artery disease. In addition to its lipid-lowering properties, statin decreases the level of CRP. Abrupt cessation of statin therapy during treatment could increase CRP level independently of the elevation of serum lipids and the incidence of cardiac events in patients with atherosclerotic heart disease. Xuezhikang (XZK), an extract of cholestin, has a marked modulating effect on lipid and CRP concentrations in different study time course. However, no attention has been paid to the changes of lipid profile and CRP concentrations after withdrawal of XZK treatment. This study was designed to explore short-term time course effects on lipid profile and CRP concentrations after withdrawal of XZK treatment in coronary heart disease patients. MATERIALS AND METHODS: Seventy-five consecutive patients with documented coronary heart disease were randomly divided into three groups: 1. Pretreatment with XZK 1,200 mg daily for 6 weeks and then replaced by placebo (XZK discontinued group; n = 25); 2. Treatment with XZK 1,200 mg daily throughout the study (XZK continued group; n = 25); or 3. Placebo (no XZK group; n = 25). Lipid levels (total cholesterol, HDL-C, LDL-C and triglycerides) and CRP were assessed before receiving the XZK therapy, 1 day before discontinuation of XZK, and on days 1, 2, 3, 7 and 14 after discontinuation of XZK, respectively. RESULTS: After 6-week XZK treatment, the fasting total cholesterol, LDL-C, triglyceride and median hs-CRP concentrations decreased, whereas HDL-C concentration increased significantly (p < 0.001, respectively). At day 14 after discontinuation of XZK therapy, total cholesterol (15%), LDL-C (17%) and triglyceride (20%) significantly increased (p < 0.001, respectively), whereas HDL-C level (15%) significantly decreased (p < 0.05). The median level of CRP increased by 11, 65, 128, 103 and 101% on the first, second, third, seventh, and fourteenth day after withdrawal of XZK therapy (p > 0.05, <0.05, <0.001, <0.001, <0.001, compared with 1 day before withdrawal of XZK therapy, respectively). There was a prominent rebound of CRP concentration 3 days after discontinuation of XZK therapy. At this time point, hs-CRP concentration was higher than in the placebo group (p < 0.05). Seven to 14 days after discontinuation of XZK therapy, the hs-CRP concentration declined to a similar level as in the placebo group. No significant correlation was seen between the changes in hs-CRP and lipid profile at all time points. CONCLUSIONS: The level of hs-CRP increases on the second day after withdrawal of XZK and there is a prominent rebound 3 days after discontinuation of XZK therapy. The increase of CRP ends within 7 days, where lipids increase at 14 days after discontinuation of XZK therapy. The results may be clinically important for patients with coronary artery disease.

Antidepressant efficacy and hormonal effects of Sudarshana Kriya Yoga (SKY) in alcohol dependent individuals.

BACKGROUND: Sudarshana Kriya Yoga (SKY) has demonstrable antidepressant effects. SKY was tested for this effect in inpatients of alcohol dependence. METHODS: Following a week of detoxification management consenting subjects (n=60) were equally randomized to receive SKY therapy or not (controls) for a two-week study. SKY therapy included alternate day practice of specified breathing exercise under supervision of a trained therapist. Subjects completed the Beck Depression Inventory (BDI) before and after the two weeks of this intervention. Morning plasma cortisol, ACTH and prolactin too were measured before and at the end of two weeks. RESULTS: In both groups reductions in BDI scores occurred but significantly more so in SKY group. Likewise, in both groups plasma cortisol as well as ACTH fell after two weeks but significantly more so in SKY group. Reduction in BDI scores correlated with that in cortisol in SKY but not in control group. LIMITATIONS: Antidepressant effects of SKY were demonstrated in early abstinence that also had substantial spontaneous improvement. It is not known if this effect contributes to sustained abstinence. CONCLUSION: Results extend the antidepressant effects of SKY in alcohol dependence subjects. Reduction in stress-hormone levels (cortisol and ACTH) along with BDI reductions possibly support a biological mechanism of SKY in producing beneficial effects.

Estimation of plasma and saliva levels of coenzyme Q10 and influence of oral supplementation.

Coenzyme Q10 (CoQ(10)) levels in human saliva were measured by HPLC with a highly sensitive electrochemical detector (ECD) and a special concentration column. This HPLC system showed satisfactory analytical results within the standard range of 0.78-50 ng/ml. We also found a significant correlation between CoQ(10) levels in plasma and in saliva from parotid glands, while this correlation was lacking between plasma CoQ10 and CoQ10 in whole saliva. Unlike in plasma, there are some fluctuations of saliva CoQ(10) levels throughout the day. A good correlation was obtained by collecting parotid gland saliva at times between meals. The mean saliva CoQ(10) level for 55 healthy volunteers was 17.0 ng/ml (S.D. 6.8 ng/ml); approximately one fiftieth of that in plasma. Regarding the influence of oral supplementation, CoQ(10) was analyzed in plasma and parotid gland saliva from 20 healthy volunteers supplemented daily with 100 mg of CoQ(10) for the first week and 200 mg for the second. The plasma CoQ(10) levels of all volunteers increased to different extents in accordance with the CoQ(10) daily intake and the corresponding change in saliva showed almost the same trend.

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.