Catecholamine response to methamphetamine is related to glucocorticoid levels but not to pleasurable subjective response.

INTRODUCTION: Corticosteroids may modulate addiction. We previously described subjective, physiological, and endocrine effects of 0.5 mg/kg of intravenous methamphetamine after augmenting cortisol level with hydrocortisone or blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone in a double-blind, balanced crossover study. Although the pharmacologic manipulations produced the expected hormonal changes, pleasurable subjective effects of methamphetamine were unchanged. Metyrapone was followed by frequent premature ventricular complexes (PVCs) in two subjects during methamphetamine administration. In order to better understand these results, we examined changes in two plasma catecholamine metabolites, homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and their relationship to the previously reported hormonal changes and physiological and subjective responses. METHODS: Plasma from 10 methamphetamine subjects from the earlier study was assayed for HVA and MHPG by high performance liquid chromatography. RESULTS: HVA levels were greater after hydrocortisone or metyrapone pretreatment compared to placebo, and MHPG levels were greater after metyrapone pretreatment. Hydrocortisone pretreatment diminished HVA and MHPG increases after methamphetamine (perhaps explaining the lack of expected increase in pleasurable effects), but metyrapone did not. HVA and MHPG concentrations were not correlated with pleasurable drug effects but were inversely related to reports of "Bad Drug Effect." Increases in MHPG and DHEA concentrations were positively correlated. Metyrapone pre-treated subjects with PVCs had lower HVA and MHPG concentrations. CONCLUSION: Raising cortisol concentration and blocking cortisol synthesis did not produce opposite effects, perhaps because of metyrapone's effect on the hypothalamic-pituitary-adrenal axis, its stress-like effects, and its effects on neurosteroids.

Sulfonium salts as derivatizing agents. 3. Quantitation of the cocaine metabolite benzoylecgonine in urine using gas chromatography with ion-pair extraction/on-column alkylation.

Recent studies have demonstrated the utility of quantitative assays for benzoylecgonine in assessing the efficacy of cocaine-dependence-treatment programs to determine if the amount of cocaine consumed has been reduced. We describe a simple gas chromatographic method for determining benzoylecgonine concentrations in urine. BZE is extracted from urine as an ion pair with tri-n-propylsulfonium ion. Injection into the heated injection port of the gas chromatograph results in thermal conversion of the ion pair to the n-propyl ester of BZE. Using the structural analogue of BZE, m-toluylecgonine, as the internal standard, the analysis is carried out on a (5% phenyl)methylpolysiloxane capillary column with nitrogen-phosphorus detection. There was a good correlation between BZE concentrations determined by gas chromatography-mass spectrometry and concentrations determined by the method described in this paper. Application to cocaine-dependence-treatment programs is discussed.

Buprenorphine pharmacokinetics: relative bioavailability of sublingual tablet and liquid formulations.

Buprenorphine is an effective new treatment for opiate dependence. This study compared the bioavailability of buprenorphine from a tablet to that from a reference solution. Six men experienced with, but not dependent on, opiates (DSM-III-R) were each administered 7.7 mg of buprenorphine in liquid form and 8 mg in tablet form 1 week apart in a balanced crossover design. Plasma levels were measured by electron capture capillary gas chromatography (GC), and concentration-time curves were constructed. Pharmacokinetic data were analyzed by analysis of variance. The bioavailability from the tablet was approximately 50% that from the liquid and was not affected by saliva pH. Lower bioavailability from the tablet may be due to slow dissolution.

Gas chromatographic determination of methamphetamine and its metabolite amphetamine in human plasma and urine following conversion to N-propyl derivatives.

A gas chromatographic method for the simultaneous determination of methamphetamine and its metabolite amphetamine in human plasma and urine is described. The method utilizes reductive alkylation with propionaldehyde and sodium borohydride to produce N-propyl derivatives, which have excellent chromatographic properties. Structural analogs of the analytes, p-methylmethamphetamine and p-methylamphetamine, are used as internal standards. The method has good precision and accuracy for concentrations ranging from less than 10 ng/ml to 5000 ng/ml and has been used to measure plasma concentrations as part of a pharmacokinetic/pharmacodynamic study of methamphetamine in humans.

The courts and elective abortions under Medicaid.

Although therapeutic or elective abortions are among the most frequently performed medical procedures for women throughout the world, indigent American women are now denied coverage under the Medicaid program because of the Hyde Amendment, which prohibits the use of federal funds for the termination of pregnancies except in narrowly defined cases. The vast majority of states, left free to choose as to the expenditure of their own funds for abortion coverage, have also denied this type of welfare assistance to economically eligible women. The discriminatory effect of the refusal to subsume abortions as part of the Medicaid mandate has been the subject of various legal actions. The constitutionality of that denial is at issue and now awaits Supreme Court determination.

PIP: Recent Supreme Court and lower court rulings related to induced abortion in the U.S. were reviewed and current issues concerning abortion availability for indigent women were discussed. As a result of the passage of the Hyde Admendment of 1977, limiting Medicaid funding for abortions, indigent women are being denied the freedom to decide whether or not to have an abortion. The Hyde Admendment permits the states to refuse to provide Medicaid funding for abortion except in cases of rape or incest. The Medicaid system was established in 1965 to provide medical care for indigent persons. Middle and upper class women who can afford abortions still have the freedom to decide to have an abortion. Furthermore, most private insurance plans provide abortion coverage. Although economic discrimination is not illegal in the U.S., racial and ethnic discrimination is illegal. Since a disproportionate number of Medicaid patients are members of racial minorities, opponents of the Admindment claim that the legislaton is illegal. Prior to 1977 the Supreme Court rulings reflected a liberal attitude toward abortion. In 1977 the Supreme Court rulings reflected a liberal attitude toward abortion. In 1977 the Supreme Court was expected to affirm the right of indigent women to receive abortion coverage under Medicaid by invoking the 14th Admendment; surprisingly, the Court did not support the rights of these women. Currently there are a number of cases in the lower courts and several are expected to reach the Supreme Court. These cases could change the current situation.

Plasma testosterone levels in heroin addiction and during methadone maintenance.

Heroin use was consistently associated with low plasma testosterone levels in narcotic addicts. Heroin addicts maintained on high dosage methadone (80-150 mg/day) also had depressed testosterone levels. Patients on low dosage methadone maintenance (10-60 mg/day) had testosterone levels which were not significant;y different from normal adult male controls. An inverse relationship between methadone dosage and plasma testosterone occurred during methadone detoxification. These findings indicate that heroin and methadone alter male androgen levels with possible derivative effects upon sexual and aggressive behaviors.