Metabolism addiction

D.W. Lachenmeier, F. Kanteres, J. Rehm, Carcinogenicity of acetaldehyde in alcoholic beverages risk assessment outside ethanol metabolism. Addiction 104 (4) (2009) 533-550. 

Hyperactivity of the orexin system, e.g. triggered by energy depletion, metabolic failure, hypoglycemia or hypoxia, in the context of starvation, sleep derivation, and stress, may predispose to addiction and... 

Personality variables, state of mind at time of withdrawal, and expectations of severity of symptoms all may affect withdrawal severity (Kleber 1981). One study found that merely providing addicts information about the withdrawal syndrome resulted in lower levels of withdrawal symptoms (Green and Gos-sop 1988). Naloxone rapidly induces a severe withdrawal syndrome, which peaks within 30 minutes and then declines rapidly. Until the antagonist is eliminated, only partial suppression of the withdrawal syndrome is possible, and then only by using very high opioid doses, which may cause respiratory depression when naloxone is metabolized. 

Dole VP, Nyswander MN Heroin addiction a metabolic disease. Arch Intern Med 120 19-24, 1967... 

Shi J, Hui L, Xu Y, et al Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat 19 459 60, 2002 Shinderman M, Maxwell S, Brawand-Arney M, etal Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses. Drug Alcohol Dependence 69 205-211, 2003... 

Petursson H, Lader MH Benzodiazepine dependence. BrJ Addict 76 133—143,1981a Petursson H, Lader MH Withdrawal from long-term benzodiazepine treatment. Br Med J (Clin Res Ed) 283 643—643, 1981b Pichard L, Gillet G, Bonfils C, et al Oxidative metabolism of zolpidem by human liver... 

Toluene, volatile nitrites, and anesthetics, like other substances of abuse such as cocaine, nicotine, and heroin, are characterized by rapid absorption, rapid entry into the brain, high bioavailability, a short half-life, and a rapid rate of metabolism and clearance (Gerasimov et al. 2002 Pontieri et al. 1996, 1998). Because these pharmacokinetic parameters are associated with the ability of addictive substances to induce positive reinforcing effects, it appears that the pharmacokinetic features of inhalants contribute to their high abuse liability among susceptible individuals. 

In the vertebrate CNS monoamines have been associated with a number of physiological functions (reviewed in Kandel et al., 1991). Serotonin has functions associated with mood, pain, sleep, learning, and memory. Dopamine has functions associated with schizophrenia, Parkinson s disease, and cocaine addiction. In vertebrates, dopamine is further metabolized into two additional neurotransmitters, norepinephrine and epinephrine. Norepinephrine increases the excitability of cells in response to sudden sensory input such as fear. Epinephrine has been identified in specific neurons of the brain, but the function of these cells is unknown. In addition, AADC has also been found in a class of neurons that do not have any of the four neurotransmitters discussed above (Jaeger et al., 1983). These neurons may use one of the trace amines, tyramine, tryptamine, or phenylethylamine, as a neurotransmitter. 

MRS research is increasingly used to indicate the regions of brain affected in addiction/alcoholism 943 MRS can provide a snapshot into the metabolic processes of brain tumors 944... 

An understanding of the pharmacology of nicotine and how nicotine produces addiction and influences smoking behavior provides a necessary basis for therapeutic advances in smoking cessation interventions. This chapter provides a review of several aspects of the human pharmacology of nicotine. These include the presence and levels of nicotine and related alkaloids in tobacco products, the absorption of nicotine from tobacco products and nicotine medications, the distribution of nicotine in body tissues, the metabolism and renal excretion of nicotine, nicotine and cotinine blood levels during tobacco use or nicotine replacement therapy, and biomarkers of nicotine exposure. For more details and references on the pharmacokinetics and metabolism of nicotine, the reader is referred to Hukkanen et al. (2005c). 

Men and women regulate their smoking differently and vary in susceptibility to nicotine addiction. Earlier data from human subjects suggested that male smokers metabolize nicotine more quickly than females (Benowitz and Jacob 1984). 

Benowitz NL, Lessov-Schlaggar CN, et al (2006) Female sex and oral contraceptive use accelerate nicotine metabolism. Clin Pharmacol Ther 79(5) 480-488 Benwell ME, Balfour DJ (1997) Regional variation in the effects of nicotine on catecholamine overflow in rat brain. Eur J Pharmacol 325(1) 13-20 Best JA, Hakstian AR (1978) A situation-specific model for smoking behavior. Addict Behav 3(2) 79-92... 

Racemic methadone (MET) is administered to heroin addicts as a substitution therapy. However, methadone enantiomers possess different pharmacological effects, and the drug has been demonstrated to be enantioselectively metabolized to its two major metabolites, 2-ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-l-pyrroline (EMDP). Stereoselective separation of MET, EDDP, and EMDP using an alpha-glycoprotein stationary phase and MS-MS detection was proposed by Kelly et al. [34]. Optimal separation conditions were 20 mM acetic acid isopropanol (93 7, pH 7.4), with a flow rate of 0.9mL/min. 

Biological changes that result from repeated drug use tolerance, addiction, adverse reactions, altered rates of drug metabolism, and so forth... 

Babies bom to opioid-addicted women also exhibit withdrawal signs, but because of the slower metabolism of opioids in the newborn, the withdrawal signs are more protracted. The babies are often treated with the opium preparation paregoric to reduce withdrawal signs. 

Dependency tests on known or suspected addictive drugs Target animal absorption, distribution, metabolism, and excretion (ADME)... 

---