Clinical characteristics of central European and North American samples of pregnant women screened for opioid agonist treatment.

BACKGROUND: Little comparable information is available regarding clinical characteristics of opioid-dependent women from different countries. In the present study, women from the USA, Canada and a Central European country, Austria, screened for participation in the Maternal Opioid Treatment Human Experimental Research study, were compared with respect to their demographic and addiction histories. METHODS: Pregnant women (n = 1,074) were screened for study participation using uniformed clinical criteria and instruments. The screening results were compared with regard to exclusion, demographics, drug use, and psychosocial and treatment histories. RESULTS: Compared to the screened US and Canadian women, Austrian women were more likely to be younger (p < 0.001), white (p < 0.001), had significantly lower levels of educational attainment (p < 0.001), were less likely to use opioids daily (p < 0.001) and more likely to have been prescribed buprenorphine (p < 0.001). Compared to both rural and urban US groups, the Austrian group was less likely to have legal issues (p < 0.001) and was younger when first prescribed agonist medication (p < 0.001). CONCLUSION: The differences between North American and European groups may offer unique insights concerning treatment and pregnancy outcomes for opioid-dependent pregnant women.

Smoking in pregnant women screened for an opioid agonist medication study compared to related pregnant and non-pregnant patient samples.

BACKGROUND: Little is known about the prevalence and severity of smoking in pregnant opioid dependent patients. OBJECTIVES: To first characterize the prevalence and severity of smoking in pregnant patients screened for a randomized controlled trial, Maternal Opioid Treatment: Human Experimental Research (MOTHER), comparing two agonist medications; and second, to compare the MOTHER screening sample to published samples of other pregnant and/or patients with substances use disorders. METHODS: Pregnant women (N = 108) screened for entry into an agonist medication comparison study were retrospectively compared on smoking variables to samples of pregnant methadone-maintained patients (N = 50), pregnant opioid or cocaine dependent patients (N = 240), non-pregnant methadone-maintained women (N = 75), and pregnant non-drug-addicted patients (N = 1,516). RESULTS: Of screened patients, 88% (n = 95) smoked for a mean of 140 months (SD = 79.0) starting at a mean age of 14 (SD = 3.5). This rate was similar to substance use disordered patients and significantly higher compared to general pregnant patients (88% vs. 22%, p < .001). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Aggressive efforts are needed to reduce/eliminate smoking in substance-abusing pregnant women.

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.

Effect of alpha-methyl-para-tyrosine on response to cocaine challenge.

This study evaluated the effect of an acute reduction in catecholamine synthesis produced by alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, on cocaine-induced euphoria. In a blinded, placebo-controlled study, AMPT (1 g p.o. T.I.D.) was given to 10 non-treatment-seeking cocaine abusers prior to intranasal administration of 2 mg/kg cocaine. AMPT, but not placebo, reduced plasma levels of the dopamine metabolite homovanillic acid and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol. AMPT also elevated prolactin levels, indicating inhibition of the tuberoinfundibular dopamine system. AMPT pretreatment produced a trend toward diminished cocaine "high" AMPT also tended to lower heart rate and blood pressure responses to cocaine, but had no effect on serum cocaine levels. Although we cannot rule out the therapeutic potential of the depletion strategy, our results with AMPT alone, at this dose, do not strongly support it.

Mazindol treatment for cocaine dependence.

This double-blind placebo-controlled treatment study tested the efficacy of mazindol in currently cocaine-dependent out-patients. Forty-three patients were randomized to mazindol (2 mg QD) vs. placebo treatment for 6 weeks. All patients received weekly group counseling. Patients improved with respect to objective (urine toxicology) and subjective (self-report of times used, dollars spent, craving, etc.) measures. There was no response difference between patients treated with mazindol and those who received placebo.

Reduction of opiate withdrawal-like symptoms by cocaine abuse during methadone and buprenorphine maintenance.

In a 6-month randomized trial comparing 125 opiate-dependent patients who were assigned to four treatment groups (2 or 6 mg of buprenorphine and 35 or 65 mg of methadone), we examined the effects of cocaine use on opiate withdrawal symptoms measured on a 25-item scale on which the scores range from 0 to 75. For the methadone-maintained patients receiving the relatively low dose (35 mg), weekly withdrawal symptoms were highest when the urine toxicology for that week indicated no cocaine use. Similar associations were found for buprenorphine. Thus, when using cocaine at a low maintenance opiate dose, persistent opiate withdrawal symptoms were reduced, which is consistent with previous naloxone-precipitated withdrawal studies. Interestingly, with a higher dose of buprenorphine (6 mg), cocaine may have increased opiate withdrawal symptoms, suggesting a possible mechanism for the reduction of illicit cocaine abuse also recently observed in another study in patients treated with high dose (120 mg) methadone maintenance. This has led to a two-component model for the relationship between cocaine and opiate withdrawal-like symptoms at high versus low opiate maintenance dose. This two-component model also reconciles the contradictory findings of prior studies.

Use of drug combinations in treatment of opioid withdrawal.

During the last 10 years new approaches for rapid opioid detoxification have included drug combinations such as clonidine and naltrexone to speed and ease the transition from opioid agonist to antagonist maintenance. Other drug combinations include naloxone with midazolam or methohexitone for inpatients, but rapid outpatient methods are more desirable. Clonidine combined with naltrexone enables abrupt opioid withdrawal in 3-5 days in an outpatient/day setting. This approach can be further improved by transition to the partial agonist buprenorphine from either heroin or methadone followed by a 1 day detoxification using naltrexone precipitated withdrawal, ameliorated by clonidine.

Evidence for ascending and descending intraspinal as well as primary sensory somatostatin projections in the rat spinal cord.

Somatostatin distribution was measured quantitatively in the rat spinal cord by radioimmunoassay. Rostro-caudally, somatostatin content was about 50% higher in lumbar-sacral cord than in cervical or thoracic levels. The dorso-ventral distribution is more uneven: somatostatin is highest in the dorsal horn, where the peptide is 15 times as concentrated as it is in the ventral white matter, the region of lowest concentration. However, measurable amounts of the peptide were found in all regions studied. Dorsal root ganglionectomy decreased somatostatin levels in the dorsal cord, supporting the previously proposed role for this peptide as a primary sensory neurotransmitter or modulator; but somatostatin content also was decreased both rostral and caudal to spinal transection, indicating the presence of ascending and descending somatostatin pathways within the spinal cord. Brain levels did not change. Met-enkephalin and substance P were also measured after the above surgical manipulations. Met-enkephalin content was not altered and substance P content was lowered significantly only after ganglionectomy. Although this study confirms the primary sensory neuron as the origin of a part of spinal cord somatostatin, it further indicates the presence of ascending and descending somatostatin pathways within the rat spinal cord.