ascorbic-acid and Substance-Withdrawal-Syndrome

Topics: Adult; Ascorbic Acid; Child; Dose-Response Relationship, Drug; Drug Interactions; Folic Acid; Humans; Niacin; Nutritional Requirements; Orthomolecular Therapy; Pantothenic Acid; Pyridoxine; Riboflavin; Solubility; Substance Withdrawal Syndrome; Substance-Related Disorders; Vitamin B Complex; Water

Sensory aspects of cigarette smoke are important for providing smoking satisfaction. In previous studies, we have found that substitution of the sensory cues of smoking with a citric acid aerosol significantly reduces craving for cigarettes and enhances smoking reduction and cessation with people trying to quit smoking cigarettes. In the current study, we conducted two clinical smoking cessation trials using an ascorbic acid aerosol as a sensory substitute. The cigarette substitute consisted of a cigarette-sized tube which delivered a fine aerosol of ascorbic acid (approx. 1 mg/puff, up to a maximum of 300 mg/day). Study 1 examined the overall effectiveness of the ascorbic acid smoking substitute device. One group of subjects which used the device and received clinical counseling was compared with another group which received only clinical counseling. The group using the device showed significantly greater abstinence rates at 3 weeks post-cessation. After the subjects stopped using the device, no difference in abstinence was detected. Study 2 was conducted to focus specifically on the role of tracheobronchial sensations in relieving craving for cigarettes. Two closely matched ascorbic acid delivery systems were compared. One device delivered fine particles of ascorbic acid that were targeted to reach the trachea, while the other delivered coarser particles of ascorbic acid that were not expected to reach the trachea or lower airways. An initial enhancement in smoking reduction was found for subjects using the fine particle device relative to those using the coarse particle device. However, by the end of treatment (5 weeks) both groups showed similar degrees of smoking reduction. For those who were abstinent from smoking at the end of treatment, craving for cigarettes and negative mood were both significantly lower for those using the fine particle device. Also, hunger for food was significantly lower in the fine particle device group. These results suggest that ascorbic acid delivered from a cigarette substitute may be effective in reducing smoking and promoting smoking abstinence.

Topics: Adult; Aerosols; Ascorbic Acid; Equipment Design; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Nicotine; Smoking Cessation; Substance Withdrawal Syndrome

Alcoholics admitted for detoxification were entered into a double blind placebo controlled trial of oral supplementation with an antioxidant cocktail (vitamin E, beta carotene, vitamin C and selenium) in order to determine the effect of this supplementation on the rate of resolution of a serum marker of free radical activity and abnormal serum biochemistry. The molar proportion of linoleic acid that was diene conjugated (a marker of free radical activity), was increased in the alcoholics 2.9% +/- 1.2 (mean +/- S.D.) compared to normal controls 1.3% +/- 0.6 (P < 0.0001) but fell at a similar rate during the first week of hospitalisation in supplemented and placebo-treated patients with a mean fall of 53.7% (+/- 16.4 S.D.) in the placebo group and 56.0% (+/- 23.7) (P = 0.32, NS) in the antioxidant supplemented group. Similarly, there was no difference in the rate of fall between serum aspartate transaminase (AST) concentration in the two groups: the placebo group falling by a mean of 68.9% (+/- 35.2) and the antioxidant supplemented group falling by 70.1% (+/- 10.0) (P = 0.41, NS) over the first 7 days of hospitalization. Alcoholics had low serum concentrations of vitamin E compared with controls (15.6 mg/l +/- 6.2 S.D.) which rose more in the supplemented group over the period of a week (7.7 mg/l +/- 4.4 to 21.6 mg/l +/- 5.1) (a mean rise of 180.5%) compared with the placebo group (8.6 mg/l +/- 6.8 to 9.6 mg/l +/- 5.7)--a mean rise of 11.6% (P = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Carotenoids; Double-Blind Method; Drug Therapy, Combination; Ethanol; Female; Free Radicals; Hematologic Tests; Humans; Liver Diseases, Alcoholic; Male; Middle Aged; Selenium; Substance Withdrawal Syndrome; Vitamin E

Topics: Alcoholism; Amitriptyline; Analysis of Variance; Anxiety; Ascorbic Acid; Chlordiazepoxide; Depression; Dose-Response Relationship, Drug; Educational Status; Humans; Intelligence Tests; Mesoridazine; Phenytoin; Psychological Tests; Substance Withdrawal Syndrome; Vitamin B Complex

Topics: Adult; Ascorbic Acid; Humans; Intellectual Disability; Male; Middle Aged; Placebos; Substance Withdrawal Syndrome; Tranquilizing Agents

Chronic morphine-induced withdrawal syndrome after morphine cessation remains a severe obstacle in the clinical treatment of morphine. Previous studies have shown that nitric oxide synthetase (NOS) inhibitors may have therapeutic potential in morphine withdrawal in humans. The mechanisms that underlie expression of morphine-induced withdrawal syndrome are, however, not yet fully understood. Therefore, this study was designed to determine the mechanism of the expression of morphine-induced withdrawal syndrome in mice. Morphine-dependent mice showed marked body weight loss and several withdrawal signs after naloxone challenge. Pretreatment with a NOS inhibitor, such as N-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole, but not aminoguanidine, significantly attenuated the expression of morphine-induced withdrawal syndrome. Furthermore, mepacrine (a phospholipase A2 inhibitor) significantly attenuated the morphine-induced withdrawal syndrome in a manner that was different than that with a NOS inhibitor. These results suggest that nNOS and phospholipase A2, which might increase free radicals, play an important role in the expression of morphine-induced withdrawal syndrome. On the contrary, free radical scavengers (including fullerenes, ascorbate-2-phosphate, and DL-alpha-tocopheryl phosphate) attenuated the expression of the morphine-induced withdrawal syndrome. These results indicate that free radicals play an important role in the expression of physical dependence on morphine, and fullerenes could be a potential clinical tool in the relief of morphine withdrawal syndrome.

Topics: alpha-Tocopherol; Animals; Ascorbic Acid; Enzyme Inhibitors; Free Radical Scavengers; Hydroxyl Radical; Male; Mice; Naloxone; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Opioid-Related Disorders; Phospholipase A2 Inhibitors; Substance Withdrawal Syndrome; Superoxides

Since ascorbic acid (AA) reportedly suppresses tolerance to and dependence on morphine in humans and rodents, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyramine (3-MT), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), AA, dehydroascorbic acid (DHAA), uric acid, xanthine, hypoxanthine, glutamate and gamma-aminobutyric acid (GABA) were determined by high-pressure liquid chromatography (HPLC) in the striatum and in the limbic forebrain of the rat following morphine treatment (single or repeated) and withdrawal. Single morphine administration (20 mg/kg s.c.) increased DOPAC + HVA/DA, 5-HIAA/5-HT and DHAA/AA ratios, uric acid levels, and decreased xanthine, hypoxanthine, glutamate and GABA levels in both regions. 3-MT levels were decreased in the striatum and increased in the limbic forebrain. After 7 days of morphine treatment, striatal DOPAC + HVA/DA and DHAA/AA ratios and uric acid levels were still higher and striatal and limbic xanthine levels still lower than in controls, while all other parameters were in the range of control values in both regions. Morphine treatment also increased the glutamate/GABA ratio in the striatum. In all morphine-treated rats, individual striatal DOPAC + HVA/DA and DHAA/AA ratio values were directly correlated. After a 48 h withdrawal period, both striatal AA oxidation and glutamate/GABA ratio further increased; limbic 3-MT levels further decreased, while all other parameters did not differ from control values. We conclude that: (i) tolerance to morphine-induced increase in hypoxanthine, xanthine and AA oxidation develops in the limbic forebrain faster than in the striatum; (ii) the morphine-induced increase in striatal and limbic AA oxidation may be considered a consequence of increased formation of reactive oxygen species due to increased DA, hypoxanthine and xanthine oxidative metabolism; (iii) a striatal excitotoxic imbalance characterizes the withdrawal state and may be taken into account to explain the further increase in striatal AA oxidation.

Topics: 3,4-Dihydroxyphenylacetic Acid; Amines; Animals; Ascorbic Acid; Corpus Striatum; Dopamine; gamma-Aminobutyric Acid; Male; Morphine; Prosencephalon; Rats; Rats, Wistar; Substance Withdrawal Syndrome

The effects of ascorbic acid (AA) were investigated on the morphine withdrawal response of guinea-pigs, a species which shares with man the inability to synthesize AA. Chronic pretreatment of guinea-pigs with AA, 1 g/l, in drinking water for 3 days, or AA 200 mg/kg subcutaneously (s.c.) 3 times daily for 3 days, markedly reduced the locomotor and behavioural withdrawal responses of guinea-pigs given naloxone hydrochloride, 15 mg/kg s.c. 2 h after a single dose of morphine sulphate, 15 mg/kg s.c. AA, 1 g/kg given intraperitoneally (i.p.) 30 min before morphine had no significant effect on morphine withdrawal. However, intracerebroventricular injection of AA, 1 mumol, 30 min before naloxone significantly enhanced morphine withdrawal. It is concluded that chronic but not acute administration of AA inhibits opiate withdrawal.

Topics: Animals; Ascorbic Acid; Drug Administration Schedule; Female; Guinea Pigs; Male; Morphine; Morphine Dependence; Motor Activity; Naloxone; Stereotyped Behavior; Substance Withdrawal Syndrome

Male guinea pigs received sodium ascorbate solution [equivalent to 1 g ascorbic acid/(kg body weight.d)] by intraperitoneal injection for 4 wk. During the ascorbic acid treatment period, plasma and urinary ascorbic acid levels rose markedly. Three weeks after the ascorbic acid treatment was withdrawn, mean urinary ascorbic acid levels were significantly lower than their corresponding basal levels. At both 2 and 5 wk after withdrawal of ascorbic acid treatment, mean plasma ascorbic acid levels were below normal. The results indicate that these animals had experienced a transient withdrawal effect after administration of large doses of ascorbic acid that lasted about 1 wk. This, in turn, indicates that the rate of ascorbic acid turnover was probably increased during treatment, and this effect persisted even after the ascorbic acid was withdrawn. Examination of data from each individual experimental animal revealed that the pattern of urinary ascorbic acid excretion after the withdrawal of large doses of ascorbic acid varied from animal to animal. Among the twelve experimental guinea pigs, seven had abnormally low urinary ascorbic acid levels 2-4 wk after the withdrawal of the large doses of ascorbic acid.

Topics: Animals; Ascorbic Acid; Dose-Response Relationship, Drug; Guinea Pigs; Male; Substance Withdrawal Syndrome; Time Factors

The influence of prolonged exposure of guinea pigs to excessive ascorbic acid (AA) on the outcome of pregnancy, as well as the adaptive effect of the vitamin either during preweanling life or following weaning, were examined. Continuous exposure to AA (1 mg/mL drinking water) from the time they were first mated up to the time of second pregnancy, had no significant effect on the number of offspring and on their weights at birth, when compared with that of the animals receiving 0.1 mg AA/mL drinking water. However, change in AA intake from 1 to 0.1 mg/mL drinking water, at the age of 21 days, resulted in a significant loss in body weight and reductions in the plasma, leukocyte, and adrenal concentrations of AA, as compared with those of the pair-fed animals receiving 0.1 mg/mL drinking water throughout. The present study also indicated that the conditioning effect is less pronounced in guinea pigs when exposed to the high AA following weanling age than in utero.

Topics: Adrenal Glands; Animals; Ascorbic Acid; Birth Weight; Body Weight; Female; Growth; Guinea Pigs; Leukocytes; Pregnancy; Substance Withdrawal Syndrome

Topics: Ascorbic Acid; Humans; Male; Middle Aged; Mouth Diseases; Orthomolecular Therapy; Scurvy; Substance Withdrawal Syndrome; Substance-Related Disorders

Following withdrawal from chronic barbital administration, 6-hydroxydopamine pretreated rats show a greater number and an earlier onset of spontaneous convulsive seizures than do rats pretreated with the saline-ascorbic acid vehicle.

Topics: Animals; Ascorbic Acid; Barbital; Barbiturates; Body Weight; Dopamine; Humans; Hydroxydopamines; Male; Norepinephrine; Rats; Seizures; Substance Withdrawal Syndrome; Substance-Related Disorders; Telencephalon

Topics: Ascorbic Acid; Common Cold; Female; Humans; Leukocytes; Pregnancy; Substance Withdrawal Syndrome

Topics: Adrenal Glands; Animals; Ascorbic Acid; Corticosterone; Humans; Male; Mitochondria; Morphine Dependence; Rats; Substance Withdrawal Syndrome

Topics: Apnea; Ascorbic Acid; Coma; Diazepam; Drug Combinations; Humans; Psychomotor Disorders; Psychoses, Substance-Induced; Substance Withdrawal Syndrome; Substance-Related Disorders; Thioctic Acid; Vitamin B Complex

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Ascorbic Acid; Corticosterone; Depression, Chemical; Dexamethasone; Humans; Male; Mitochondria; Morphine; Morphine Dependence; Rats; Stimulation, Chemical; Substance Withdrawal Syndrome

Topics: Alcoholics; Alcoholism; Ascorbic Acid; Substance Withdrawal Syndrome; Vitamin B Complex