Papers by Marilyn Huestis
Neurotoxicology and Teratology, 2011
The primary purpose of this study was to examine pathways from prenatal cigarette exposure to phy... more The primary purpose of this study was to examine pathways from prenatal cigarette exposure to physiological regulation at 2 months of age. Specifically, we explored the possibility that any association between prenatal cigarette exposure and infant physiological regulation was moderated by fetal growth, prenatal or postnatal environmental tobacco smoke (ETS) exposure or maternal depressive symptomatology during pregnancy. We evaluated whether exposed infants who were also exposed to ETS after birth, were small for gestational age (SGA) or had mothers with higher depressive symptoms during pregnancy had the highest levels of physiological dysregulation. Respiratory sinus arrhythmia (RSA) was obtained from 234 (166 exposed and 68 nonexposed) infants during sleep. As expected, cigarette-exposed infants had significantly lower RSA than nonexposed infants. This association was not moderated by prenatal or postnatal ETS exposure, or maternal depressive symptomatology during pregnancy. However, small for gestational age status did moderate this association such that nonexposed infants who were not small for gestational age had a significantly higher RSA than nonexposed small for gestational age infants and exposed infants. These findings provide additional evidence that prenatal cigarette exposure is directly associated with dysregulation during infancy.
Developmental psychobiology, 2015
This study examined the association between prenatal tobacco exposure (PTE) and infant cortisol r... more This study examined the association between prenatal tobacco exposure (PTE) and infant cortisol reactivity at 9 months of infant age. Child sex and maternal parenting behavior were hypothesized moderators. The sample included 217 (148 tobacco-exposed, 69 non-exposed) mother-child dyads. Data used were obtained from pregnancy assessments, mother-infant feeding interactions at 2 months, and salivary cortisol at four time points in response to frustration at 9 months. Results indicated a significant association between PTE and infant cortisol that was moderated by infant sex and maternal intrusiveness. That is, PTE boys had lower cortisol than control boys, but there was no association between PTE and cortisol among girls. There was a significant association between PTE and cortisol among infants of intrusive mothers, but not among infants with non-intrusive mothers. Thus, PTE was associated with cortisol hypo-reactivity such that boys and non-exposed infants experiencing high maternal...
Infancy, 2013
The primary purpose of this study was to examine the association between prenatal cigarette expos... more The primary purpose of this study was to examine the association between prenatal cigarette exposure and physiological regulation at 9 months of age. Specifically, we explored the possibility that any association between prenatal cigarette exposure and infant physiological regulation was moderated by postnatal environmental tobacco smoke (ETS) exposure or infant gender. We evaluated whether male infants with prenatal cigarette exposure or infants who were also exposed to ETS after birth had the highest levels of physiological dysregulation. Respiratory sinus arrhythmia (RSA) was obtained from 206 (142 exposed and 64 nonexposed) infants during a baseline period and during procedures designed to elicit both positive and negative affect. There was a significant suppression of RSA during the negative affect task for nonexposed infants but not for exposed infants. Postnatal ETS exposure did not moderate this association; however, gender did moderate this association such that boys with prenatal cigarette exposure had a significant increase in RSA rather than the suppression seen among both nonexposed boys and girls. These results provide additional support for the idea that boys are particularly vulnerable to the effects of prenatal cigarette exposure.
Journal of Studies on Alcohol and Drugs, 2011
Objective: We examined the role of anger, hostility, and aggression, in addition to depression an... more Objective: We examined the role of anger, hostility, and aggression, in addition to depression and stress, in predicting persistent smoking during pregnancy in a low-income sample. Method: The sample consisted of 270 pregnant women (189 smokers, 81 nonsmokers) recruited into a prospective study of prenatal cigarette exposure in the fi rst trimester. Persistent pregnancy smoking was defi ned as self-reporting daily smoking in at least two trimesters, a positive salivary cotinine level in at least two trimesters, or infant meconium positive for nicotine and/ or its metabolites. Results: Persistent smokers reported higher prenatal stress and negative affect symptoms (depression, anger, hostility, ag-gression) than nonpersistent smokers or nonsmokers. However, in the context of model testing, maternal anger, hostility, and aggression each accounted for unique variance in persistent smoking, whereas symptoms of depression and stress did not. Conclusions: To date, interventions for pregnant low-income smokers have been largely ineffective. The current results suggest that anger management interventions may be particularly effective for low-income persistent pregnant smokers and may be more likely to prevent relapse than depression-focused interventions. (J. Stud. Alcohol Drugs, 72, 926-932, 2011)
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jan 26, 2015
The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to t... more The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) and COT to trans-3'-hydroxycotinine (3HC). The nicotine metabolite ratio (NMR, 3HC/COT) is commonly used as a biomarker of CYP2A6 enzymatic activity, rate of nicotine metabolism, and total nicotine clearance; NMR is associated with numerous smoking phenotypes, including smoking cessation. Our objective was to investigate the impact of different measurement methods, at different sites, on plasma and urinary NMR measures from ad libitum smokers. Plasma (n=35) and urine (n=35) samples were sent to eight different laboratories, which employed similar and different methods of COT and 3HC measurements to derive the NMR. We used Bland-Altman analysis to assess agreement, and Pearson correlations to evaluate associations, between NMR measured by different methods. Measures of plasma NMR were in strong agreement between methods according to Bland-Altman analysis (ratios 0.82-1.16) and were highly correla...
Therapeutic drug monitoring, 2009
The Infant Development Environment and Lifestyle study is investigating the effects of prenatal m... more The Infant Development Environment and Lifestyle study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration, and magnitude of maternal MAMP exposure affect qualitative and quantitative meconium results. Interviews regarding maternal drug use were collected shortly after birth; meconium specimens were screened for amphetamines, cannabis, and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry. The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) me...
Neurotoxicology and Teratology, 2015
The purpose of this study was to examine the association between prenatal exposure to cigarettes ... more The purpose of this study was to examine the association between prenatal exposure to cigarettes and heart rate during an object manipulation task at 9 months of age. Second-by-second heart rate was recorded for 181 infants who were prenatally exposed to cigarettes and 77 nonexposed infants during the manipulation of four standardized toys. A series of longitudinal multilevel models were run to examine the association of prenatal smoking on the intercept and slope of heart rate during four 90-second object manipulation tasks. After controlling for maternal age, prenatal marijuana and alcohol use, duration of focused attention and activity level, results indicated that the heart rates of exposed infants significantly increased during the object manipulation task. These findings suggest casual rather than focused attention and a possible increase in physiological arousal during object manipulation.
Neuroscience, 2001
In order to examine differential strain susceptibility to neurotoxic effects of amphetamine and t... more In order to examine differential strain susceptibility to neurotoxic effects of amphetamine and to assess the potential role of superoxide radicals in amphetamine-induced dopaminergic damage, the drug was injected to mice with different levels of copper/zinc superoxide dismutase (Cu/Zn SOD) enzyme. Administration of amphetamine (10 mg/kg, i.p., given every 2 h, a total of four times) to wild-type CD-1 and C57BL/6J mice caused significant decreases in dopamine and 3,4-dihydroxyphenylacetic acid levels, in [(125)I]RTI-121-labeled dopamine transporters as well as a significant depletion in the concentration of dopamine transporter and vesicular monoamine transporter 2 proteins. The amphetamine-induced toxic effects were less prominent in CD-1 mice, which have much higher levels of Cu/Zn SOD activity (0.69 units/mg of protein) in their striata than C57BL/6J animals (0.007 units/mg of protein). Transgenic mice on CD-1 and C57BL/6J background, which had striatal levels of Cu/Zn SOD 2.57 a...
Molecular pharmacology, 2000
Increasing evidence implicates apoptosis as a major mechanism of cell death in methamphetamine (M... more Increasing evidence implicates apoptosis as a major mechanism of cell death in methamphetamine (METH) neurotoxicity. The involvement of a neuroimmune component in apoptotic cell death after injury or chemical damage suggests that cytokines may play a role in METH effects. In the present study, we examined if the absence of IL-6 in knockout (IL-6-/-) mice could provide protection against METH-induced neurotoxicity. Administration of METH resulted in a significant reduction of [(125)I]RTI-121-labeled dopamine transporters in the caudate-putamen (CPu) and cortex as well as depletion of dopamine in the CPu and frontal cortex of wild-type mice. However, these METH-induced effects were significantly attenuated in IL-6-/- animals. METH also caused a decrease in serotonin levels in the CPu and hippocampus of wild-type mice, but no reduction was observed in IL-6-/- animals. Moreover, METH induced decreases in [(125)I]RTI-55-labeled serotonin transporters in the hippocampal CA3 region and in ...
Journal of analytical toxicology, 1993
Recently, a number of "quick tests" became available for use in on-site drug testing. T... more Recently, a number of "quick tests" became available for use in on-site drug testing. These tests offer advantages in simplicity, ease of performance, and rapid access to test results. However, there is a paucity of data on the validity of these tests for the detection of drugs of abuse. This report describes a validity study of the EZ-SCREEN cannabinoid test for the detection of cannabinoids in urine. Three healthy, male volunteers with a history of marijuana use participated in the study. Each subject smoked 1, 2, or 4 marijuana cigarettes (2.6% THC) on each test day. Urine samples were collected and incorporated into a specimen set consisting of 178 clinical urine samples, 72 urine samples containing known amounts of drug, and 50 drug-free urine samples. The specimen set was randomized and analyzed under blind conditions by the EZ-SCREEN test and by GC/MS for 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH). Results were interpreted independently by three readers...
This study investigated the prospective association between prenatal methamphetamine (MA) exposur... more This study investigated the prospective association between prenatal methamphetamine (MA) exposure and child behavioral problems at 5 years while also examining the home environment at 30 months and several primary caregiver (PC) risk factors. Participants were 97 MA-exposed and 117 comparison children and their PCs enrolled in the Infant Development, Environment and Lifestyle Study. Hypotheses were that child behaviors would be adversely impacted by (a) prenatal MA exposure, (b) home environments that provided less developmental stimulation and emotional responsiveness to the child, and (c) the presence of PC psychological symptoms and other risk factors. Prenatal MA exposure was associated with child externalizing behavioral problems at 5 years. Home environments that were more conducive to meeting children's developmental and emotional needs were associated with fewer internalizing and externalizing behavioral problems. Independent of prenatal MA exposure, PC parenting stress and psychological symptoms were associated with increased child behavioral problems. Findings suggest prenatal MA exposure may contribute to externalizing behavioral problems in early childhood and the importance of considering possible vulnerabilities related to prenatal MA exposure in the context of the child's caregiving environment.
A positive chemical ionization gas chromatography-mass spectrometric method was validated to simu... more A positive chemical ionization gas chromatography-mass spectrometric method was validated to simultaneously quantify drugs and metabolites in skin collected after controlled administration of methamphetamine, cocaine, and codeine. Calibration curves (2.5-100 ng/skin biopsy) for methamphetamine, amphetamine, cocaine, norcocaine, benzoylecgonine, cocaethylene, norcocaethylene, anhydroecgonine methyl ester, morphine, codeine, and 6-acetylmorphine (5-100 ng/skin biopsy for ecgonine methyl ester and ecgonine ethyl ester) exhibited correlation coefficients >0.999 and concentrations ±20% of target. Intra-and inter-run precisions were <10%. This procedure should be useful for postmortem analysis; data are included on drug concentrations in skin after controlled drug administration. .gov (M.A. Huestis). and weigh approximately 50 mg/skin biopsy. Skin is composed of two main layers, the outer and inner dermis. The top layer of the epidermis, stratum corneum, is composed of dead, flat skin cells that are shed about every 2 weeks. The dermis contains blood vessels, hair follicles, glands, and fat tissue. These glands produce sweat and sebum, an oily substance that prevents dehydration of the skin. An excretory duct from the sweat gland discharges sweat through pores onto the surface of the skin. Sebaceous glands deposit sebum onto hair follicles. Skin is constantly exposed to sweat and sebum and drugs in these secretions may be sequestered in skin and hair . There also is evidence that after chronic exposure, lipophilic drugs may be stored in adipose tissue creating a drug depot and extending the exposure window .
The proanthocyanidins in three foods (pinto beans, plums and cinnamon) were studied with electros... more The proanthocyanidins in three foods (pinto beans, plums and cinnamon) were studied with electrospray ionization (ESI) mass spectrometry (MS) in the negative mode following separation by normal-phase high-performance liquid downatography.
Schizophrenia research, 2014
Drug testing and analysis, Jan 17, 2014
Synthetic cannabinoid intake is an ongoing health issue worldwide, with new compounds continually... more Synthetic cannabinoid intake is an ongoing health issue worldwide, with new compounds continually emerging, making drug testing complex. Parent synthetic cannabinoids are rarely detected in urine, the most common matrix employed in workplace drug testing. Optimal identification of synthetic cannabinoid markers in authentic urine specimens and correlation of metabolite concentrations and toxicities would improve synthetic cannabinoid result interpretation. We screened 20 017 randomly collected US military urine specimens between July 2011 and June 2012 with a synthetic cannabinoid immunoassay yielding 1432 presumptive positive specimens. We analyzed all presumptive positive and 1069 negative specimens with our qualitative synthetic cannabinoid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which confirmed 290 positive specimens. All 290 positive and 487 randomly selected negative specimens were quantified with the most comprehensive urine quantitative LC-MS/MS meth...
Journal of chromatography. B, Biomedical sciences and applications, Jan 15, 1999
Sweat testing for drugs of abuse provides a convenient and considerably less invasive method for ... more Sweat testing for drugs of abuse provides a convenient and considerably less invasive method for monitoring drug exposure than blood or urine. Numerous devices have been developed for collection of sweat specimens. The most common device in current use is the PharmChek Sweat Patch, which usually is worn by an individual for five to ten days. This device has been utilized in several field trials comparing sweat test results to conventional urinalysis and the results have been favorable. Two new Fast Patch devices have been developed and tested that allow rapid collection of sweat specimens. The Hand-held Fast Patch was applied to the palm of the hand and the Torso Fast Patch was applied to the abdomen or the sides of the trunk (flanks) of volunteer subjects participating in a research study. Both patches employed heat-induced sweat stimulation and a larger cellulose pad for increased drug collection. Sweat specimens were collected for 30 min at various times following administration ...
Clinical chemistry, 2002
Confirmation of a workplace drug test requires urinary methamphetamine (MAMP) and amphetamine (AM... more Confirmation of a workplace drug test requires urinary methamphetamine (MAMP) and amphetamine (AMP) concentrations > or = 500 and 200 micro g/L, respectively, but cutoffs at half those values (250/100 micro g/L) have been proposed. We determined the urinary excretion of MAMP after oral ingestion and examined the effect of using lower cutoffs on detection of exposure. Volunteers (n = 8) ingested four 10-mg doses of MAMP. HCl daily over 7 days, and five of them ingested four 20-mg doses 4 weeks later. After ingestion, the volunteers collected all urine specimens for 2 weeks. After solid-phase extraction, MAMP and AMP were measured by gas chromatography-positive chemical ionization mass spectrometry with dual silyl derivatization. MAMP and AMP were generally detected in the first or second void (0.7-11.3 h) collected after drug administration, with concentrations of 82-1827 and 12-180 micro g/L, respectively. Peak MAMP concentrations (1871-6004 micro g/L) after single doses occurred...
Clinical chemistry, 2002
The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alt... more The ease, noninvasiveness, and safety of oral fluid collection have increased the use of this alternative matrix for drugs-of-abuse testing; however, few controlled drug administration data are available to aid in the interpretation of oral fluid results. Single oral codeine doses (60 and 120 mg/70 kg) were administered to 19 volunteers. Oral fluid and plasma were analyzed for free codeine, norcodeine, morphine, and normorphine by solid-phase extraction combined with gas chromatography-mass spectrometry (SPE/GC-MS). Physiologic and subjective effects were examined. Mean (SE) peak codeine concentrations were 214.2 +/- 27.6 and 474.3 +/- 77.0 micro g/L in plasma and 638.4 +/- 64.4 and 1599.3 +/- 241.0 micro g/L in oral fluid. The oral fluid-to-plasma ratio for codeine was relatively constant ( approximately 4) from 1 to 12 h. The mean half-life (t(1/2)) of codeine was 2.2 +/- 0.10 h in plasma and 2.2 +/- 0.16 h in oral fluid. Significant dose-related miosis and increases in sedation, ...
Background: Characterization of opioid excretion in sweat is important for accurate interpretatio... more Background: Characterization of opioid excretion in sweat is important for accurate interpretation of sweat tests in drug treatment, criminal justice, and workplace drug testing programs. Methods: Participants (n ؍ 20) received placebo, 3 low (60 mg/70 kg) or 3 high (120 mg/70 kg) codeine sulfate doses (used as a model for opioid excretion) within 1 week. Codeine and metabolites in sweat were collected with PharmChek ® Sweat Patches; hourly patches were applied for 1 to 15 h (n ؍ 775) and weekly patches for 7 days (n ؍ 118). Patches were analyzed by solid-phase extraction and gas chromatography-mass spectrometry for codeine, norcodeine, morphine, normorphine, and 6-acetylmorphine. Limits of quantification were 2.5 ng/ patch (codeine and morphine) and 5 ng/patch (other analytes). Results: Codeine was the only analyte identified in 12.6% of hourly patches and 83.3% of weekly sweat patches worn during dosing. Weekly patch concentrations (SD) were 38.6 (59.9) ng/patch [median (range), 15.9 (0 -225.1) ng/patch] for low and 34.1 (32.7) ng/patch [24.0 (0 -96.2) ng/patch] for high codeine doses. Codeine detected 1 week after dosing was 4.6 (5.3) ng/patch [median (range), 4.0 (0 -17.1) ng/patch; n ؍ 11] after low and 7.7 (7.1) ng/patch [6.9 (0 -20.5) ng/patch; n ؍ 10] after high doses. In total, 2.6% of hourly, 38.5% of low-dose, and 45.5% of high-dose weekly patches contained codeine at the proposed Substance Abuse and Mental Health Services Administration cutoff. Conclusions: Codeine was the only analyte detected, at highly variable concentrations, up to 2 weeks after dosing. These results are consistent, considering the complex processes of codeine deposition in sweat. Sweat testing is a useful alternative technique for qualitative monitoring of opioid use.
Uploads
Papers by Marilyn Huestis