Marilyn Huestis | University of Maryland School of Medicine (original) (raw)

Professor Dr. Dr. (h.c.) Marilyn A. Huestis recently retired as a tenured senior investigator and Chief, Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, National Institutes of Health, after 23 years of conducting controlled drug administration studies. She is an Adjunct Professor, University of Maryland Baltimore School of Medicine. She thoroughly enjoys mentoring doctoral students in Toxicology. Her research program focuses on discovering mechanisms of action of cannabinoid agonists and antagonists, effects of in utero drug exposure, the neurobiology and pharmacokinetics of novel psychoactive substances, and driving under the influence of drugs. She has published 430 peer-reviewed manuscripts and book chapters and hundreds of abstracts were presented at national and international meetings. Professor Huestis received a bachelor's degree in biochemistry from Mount Holyoke College, a master's degree in clinical chemistry from the University of New Mexico, and a doctoral degree in toxicology from the University of Maryland. Professor Huestis received a Doctor Honoris Causa from the Faculty of Medicine, University of Helsinki in Finland. Other important awards include, 2016 Marian W. Fischman Lectureship Award from the College on Problems of Drug Dependence, 2016 Saferstein Memorial Distinguished Lecturer at Northeastern University to be awarded April 2016, Excellence in Scientific Research, Norman P. Kubasik Lectureship Award, AACC Upstate New York Section May 7, 2015, Distinguished Fellow Award from the American Academy of Forensic Sciences (AAFS) in 2015, The International Association of Forensic Toxicologists (TIAFT) Alan Curry Award in 2010, the American Association for Clinical Chemistry Outstanding Contributions in a Selected Area of Research Award in 2008, the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) Irving Sunshine Award in 2007, the AAFS Rolla N. Harger Award in 2005, and the Irving Sunshine Award for Outstanding Research in Forensic Toxicology in 1992. The journal Clinical Chemistry featured her as an “Inspiring Mind”. She currently serves on the National Commission on Forensic Sciences, and the Organization of Scientific Area Committee on Toxicology, World Anti-doping Agency’s Prohibited List Committee, Transportation Research Board Committee on Alcohol and Other Drugs, and the National Safety Council’s Alcohol, Drugs and Impairment Division Executive Board. She is past president of the Society of Forensic Toxicologists, past Chair of the Toxicology Section of the American Academy of Forensic Sciences, and the first woman president of The International Association of Forensic Toxicologists.

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Papers by Marilyn Huestis

Research paper thumbnail of Comparative Pharmacokinetics of Δ<sup>9</sup>-Tetrahydrocannabinol in Adolescent and Adult Male Mice

Journal of Pharmacology and Experimental Therapeutics, Apr 28, 2020

Research paper thumbnail of Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study

Translational Psychiatry, Feb 19, 2020

Research paper thumbnail of Respiratory effects of oral mitragynine and oxycodone in a rodent model

Psychopharmacology, Oct 29, 2022

Research paper thumbnail of Development and validation of a liquid chromatography mass spectrometry assay for the simultaneous quantification of methadone, cocaine, opiates and metabolites in human umbilical cord

Journal of Chromatography B, Oct 1, 2009

Research paper thumbnail of Identification of ∆9-tetrahydrocannabinol (THC) impairment using functional brain imaging

Neuropsychopharmacology, Jan 8, 2022

Research paper thumbnail of Recommendations for Toxicological Investigation of Drug-Impaired Driving and Motor Vehicle Fatalities—2017 Update

Journal of Analytical Toxicology, Nov 23, 2017

Research paper thumbnail of Data from Nicotine Metabolite Ratio (3-Hydroxycotinine/Cotinine) in Plasma and Urine by Different Analytical Methods and Laboratories: Implications for Clinical Implementation

Background: The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) ... more Background: 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.Methods: Plasma (n = 35) and urine (n = 35) samples were sent to eight different laboratories, which used 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.Results: Measures of plasma NMR were in strong agreement between methods according to Bland–Altman analysis (ratios, 0.82–1.16...

Research paper thumbnail of Kratom withdrawal: Discussions and conclusions of a scientific expert forum

Drug and Alcohol Dependence Reports

Research paper thumbnail of Nasal Accumulation and Metabolism of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration in Adolescent Rats

Research paper thumbnail of 4-Hydroxy-N,N-methylpropyltryptamine (4-OH-MPT) in vitro human metabolism

Toxicologie Analytique et Clinique

Research paper thumbnail of Effects of subtoxic 3-methylmethcathinone concentrations on neuronal cell electrical properties

Toxicologie Analytique et Clinique

Research paper thumbnail of Nicotine metabolite ratio in plasma and urine by different analytical methods and laboratories: Implications for clinical implementation

Research paper thumbnail of Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers

Journal of Analytical Toxicology, 2021

Increased prevalence of cannabis consumption and impaired driving are a growing public safety con... more Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified blood concentration of ∆9-tetrahydrocannabinol (THC) in a biological fluid (typically blood). Blood THC concentrations decrease significantly (∼90%) with delays in specimen collection, suggesting the use of alternative matrices, such as oral fluid (OF). We characterized 10 cannabinoids’ concentrations, including THC metabolites, in blood and OF from 191 frequent and occasional users by liquid chromatography with tandem mass spectrometry for up to 6 h after ad libitum smoking. Subjects self-titrated when smoking placebo, 5.9 or 13.4% THC cannabis. Higher maximum blood THC concentrations (Cmax) were observed in individuals who received the 5.9% THC versus the 13.4% THC plant material. In blood, the Cmax of multiple analytes, including THC and its metabolites, were increased in frequent comp...

Research paper thumbnail of Pharmacokinetic, behavioral, and brain activity effects of Δ9-tetrahydrocannabinol in adolescent male and female rats

Neuropsychopharmacology, 2020

Research paper thumbnail of Combined effect of alcohol and cannabis on simulated driving

Psychopharmacology, 2021

RATIONALE With alcohol and cannabis remaining the most commonly detected drugs in seriously and f... more RATIONALE With alcohol and cannabis remaining the most commonly detected drugs in seriously and fatally injured drivers, there is a need to understand their combined effects on driving. OBJECTIVES The present study examined the effects of combinations of smoked cannabis (12.5% THC) and alcohol (target BrAC 0.08%) on simulated driving performance, subjective drug effects, cardiovascular measures, and self-reported perception of driving ability. METHODS In this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial, cannabis users (1-7 days/week) aged 19-29 years attended four drug administration sessions in which simulated driving, subjective effects, cardiovascular measures, and whole blood THC and metabolite concentrations were assessed following placebo alcohol and placebo cannabis (<0.1% THC), alcohol and placebo cannabis, placebo alcohol and active cannabis, and alcohol and active cannabis. RESULTS Standard deviation of lateral position in the combined condition was significantly different from the placebo condition (p < 0.001). Standard deviation of lateral position was also significantly different from alcohol and cannabis alone conditions in the single task overall drive (p = 0.029 and p = 0.032, respectively), from the alcohol alone condition in the dual task overall drive (p = 0.022) and the cannabis alone condition in the dual task straightaway drive (p = 0.002). Compared to the placebo condition, the combined and alcohol conditions significantly increased reaction time. Subjective effects in the combined condition were significantly greater than with either of the drugs alone at some time points, particularly later in the session. A driving ability questionnaire showed that participants seemed unaware of their level of impairment. CONCLUSION Combinations of alcohol and cannabis increased weaving and reaction time, and tended to produce greater subjective effects compared to placebo and the single drug conditions suggesting a potential additive effect. The fact that participants were unaware of this increased effect has important implications for driving safety.

Research paper thumbnail of Subtherapeutic Acetazolamide Doses as a Noninvasive Method for Assessing Medication Adherence

Clinical Pharmacology & Therapeutics, 2020

Adherence monitoring is a vital component of clinical efficacy trials, as the regularity of medic... more Adherence monitoring is a vital component of clinical efficacy trials, as the regularity of medication consumption affects both efficacy and adverse effect profiles. Pill‐counts do not confirm consumption, and invasive plasma assessments can only assist post hoc assessments. We previously reported on the pharmacokinetics of a potential adherence marker to noninvasively monitor dosage consumption during a trial without breaking a blind. We reported that consumption cessation of subtherapeutic 15 mg acetazolamide (ACZ) doses showed a predictable urinary excretion decay that was quantifiable for an extended period. The current study describes the clinical implementation of 15 mg ACZ doses as an adherence marker excipient in distinct cohorts taking ACZ for different “adherence” durations. We confirm that ACZ output did not change (accumulate) during 18–20 days of adherence, and developed and assessed urinary cutoffs as nonadherence indicators. We demonstrate that whereas an absolute con...

Research paper thumbnail of Miniaturized extraction method for analysis of synthetic opioids in urine by microextraction with packed sorbent and liquid chromatography—tandem mass spectrometry

Journal of Chromatography A, 2020

Synthetic opioids are responsible for numerous overdoses and fatalities worldwide. Currently, fen... more Synthetic opioids are responsible for numerous overdoses and fatalities worldwide. Currently, fentanyl and its analogs are also mixed with heroin, cocaine and methamphetamine, or sold as oxycodone, hydrocodone and alprazolam in counterfeit medications. Microextraction techniques became more frequent in analytical toxicology over the last decade. A method to simultaneously quantify nine synthetic opioids, fentanyl, sufentanil, alfentanil, acrylfentanyl, thiofentanyl, valerylfentanyl, furanylfentanyl, acetyl fentanyl and carfentanil, and two metabolites, norfentanyl and acetyl norfentanyl, in urine samples by microextraction with packed sorbent (MEPS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated. A multivariate optimization was performed to establish the number and speed (stroke) of draw-eject sample cycles and the extraction solvent. The best extraction condition was eight draw-eject sample cycles, with a velocity of 3.6 µL/sec and acetonitrile as elution solvent. Linearity was achieved between 1 to 100 ng/mL, with a limit of detection (LOD) of 0.1 ng/mL and limit of quantification (LOQ) of 1 ng/mL. Imprecision (% relative standard deviation) and bias (%) were less than 12.8% and 5.7%, respectively. The method had good specificity and selectivity when challenged with 10 different matrix sources and 36 pharmaceuticals and drugs of abuse at concentrations of 100 or 500 ng/mL. The method was successfully applied to authentic urine samples. MEPS was an efficient semi-automatic extraction technique, requiring small volumes of organic solvents (640 µL) and sample (200 µL). The cartridges can be cleaned and reused (average of 150 sample extractions/barrel inside and needle).

Research paper thumbnail of The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda

Drug and Alcohol Dependence, 2020

Research paper thumbnail of Measuring Within-Individual Cannabis Reduction in Clinical Trials: a Review of the Methodological Challenges

Current Addiction Reports, 2019

Research paper thumbnail of Prenatal exposure to tobacco and cannabis: Effects on autonomic and emotion regulation

Neurotoxicology and Teratology, 2018

Research paper thumbnail of Comparative Pharmacokinetics of Δ<sup>9</sup>-Tetrahydrocannabinol in Adolescent and Adult Male Mice

Journal of Pharmacology and Experimental Therapeutics, Apr 28, 2020

Research paper thumbnail of Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study

Translational Psychiatry, Feb 19, 2020

Research paper thumbnail of Respiratory effects of oral mitragynine and oxycodone in a rodent model

Psychopharmacology, Oct 29, 2022

Research paper thumbnail of Development and validation of a liquid chromatography mass spectrometry assay for the simultaneous quantification of methadone, cocaine, opiates and metabolites in human umbilical cord

Journal of Chromatography B, Oct 1, 2009

Research paper thumbnail of Identification of ∆9-tetrahydrocannabinol (THC) impairment using functional brain imaging

Neuropsychopharmacology, Jan 8, 2022

Research paper thumbnail of Recommendations for Toxicological Investigation of Drug-Impaired Driving and Motor Vehicle Fatalities—2017 Update

Journal of Analytical Toxicology, Nov 23, 2017

Research paper thumbnail of Data from Nicotine Metabolite Ratio (3-Hydroxycotinine/Cotinine) in Plasma and Urine by Different Analytical Methods and Laboratories: Implications for Clinical Implementation

Background: The highly genetically variable enzyme CYP2A6 metabolizes nicotine to cotinine (COT) ... more Background: 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.Methods: Plasma (n = 35) and urine (n = 35) samples were sent to eight different laboratories, which used 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.Results: Measures of plasma NMR were in strong agreement between methods according to Bland–Altman analysis (ratios, 0.82–1.16...

Research paper thumbnail of Kratom withdrawal: Discussions and conclusions of a scientific expert forum

Drug and Alcohol Dependence Reports

Research paper thumbnail of Nasal Accumulation and Metabolism of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration in Adolescent Rats

Research paper thumbnail of 4-Hydroxy-N,N-methylpropyltryptamine (4-OH-MPT) in vitro human metabolism

Toxicologie Analytique et Clinique

Research paper thumbnail of Effects of subtoxic 3-methylmethcathinone concentrations on neuronal cell electrical properties

Toxicologie Analytique et Clinique

Research paper thumbnail of Nicotine metabolite ratio in plasma and urine by different analytical methods and laboratories: Implications for clinical implementation

Research paper thumbnail of Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers

Journal of Analytical Toxicology, 2021

Increased prevalence of cannabis consumption and impaired driving are a growing public safety con... more Increased prevalence of cannabis consumption and impaired driving are a growing public safety concern. Some states adopted per se driving laws, making it illegal to drive with more than a specified blood concentration of ∆9-tetrahydrocannabinol (THC) in a biological fluid (typically blood). Blood THC concentrations decrease significantly (∼90%) with delays in specimen collection, suggesting the use of alternative matrices, such as oral fluid (OF). We characterized 10 cannabinoids’ concentrations, including THC metabolites, in blood and OF from 191 frequent and occasional users by liquid chromatography with tandem mass spectrometry for up to 6 h after ad libitum smoking. Subjects self-titrated when smoking placebo, 5.9 or 13.4% THC cannabis. Higher maximum blood THC concentrations (Cmax) were observed in individuals who received the 5.9% THC versus the 13.4% THC plant material. In blood, the Cmax of multiple analytes, including THC and its metabolites, were increased in frequent comp...

Research paper thumbnail of Pharmacokinetic, behavioral, and brain activity effects of Δ9-tetrahydrocannabinol in adolescent male and female rats

Neuropsychopharmacology, 2020

Research paper thumbnail of Combined effect of alcohol and cannabis on simulated driving

Psychopharmacology, 2021

RATIONALE With alcohol and cannabis remaining the most commonly detected drugs in seriously and f... more RATIONALE With alcohol and cannabis remaining the most commonly detected drugs in seriously and fatally injured drivers, there is a need to understand their combined effects on driving. OBJECTIVES The present study examined the effects of combinations of smoked cannabis (12.5% THC) and alcohol (target BrAC 0.08%) on simulated driving performance, subjective drug effects, cardiovascular measures, and self-reported perception of driving ability. METHODS In this within-subjects, double-blind, double-dummy, placebo-controlled, randomized clinical trial, cannabis users (1-7 days/week) aged 19-29 years attended four drug administration sessions in which simulated driving, subjective effects, cardiovascular measures, and whole blood THC and metabolite concentrations were assessed following placebo alcohol and placebo cannabis (<0.1% THC), alcohol and placebo cannabis, placebo alcohol and active cannabis, and alcohol and active cannabis. RESULTS Standard deviation of lateral position in the combined condition was significantly different from the placebo condition (p < 0.001). Standard deviation of lateral position was also significantly different from alcohol and cannabis alone conditions in the single task overall drive (p = 0.029 and p = 0.032, respectively), from the alcohol alone condition in the dual task overall drive (p = 0.022) and the cannabis alone condition in the dual task straightaway drive (p = 0.002). Compared to the placebo condition, the combined and alcohol conditions significantly increased reaction time. Subjective effects in the combined condition were significantly greater than with either of the drugs alone at some time points, particularly later in the session. A driving ability questionnaire showed that participants seemed unaware of their level of impairment. CONCLUSION Combinations of alcohol and cannabis increased weaving and reaction time, and tended to produce greater subjective effects compared to placebo and the single drug conditions suggesting a potential additive effect. The fact that participants were unaware of this increased effect has important implications for driving safety.

Research paper thumbnail of Subtherapeutic Acetazolamide Doses as a Noninvasive Method for Assessing Medication Adherence

Clinical Pharmacology & Therapeutics, 2020

Adherence monitoring is a vital component of clinical efficacy trials, as the regularity of medic... more Adherence monitoring is a vital component of clinical efficacy trials, as the regularity of medication consumption affects both efficacy and adverse effect profiles. Pill‐counts do not confirm consumption, and invasive plasma assessments can only assist post hoc assessments. We previously reported on the pharmacokinetics of a potential adherence marker to noninvasively monitor dosage consumption during a trial without breaking a blind. We reported that consumption cessation of subtherapeutic 15 mg acetazolamide (ACZ) doses showed a predictable urinary excretion decay that was quantifiable for an extended period. The current study describes the clinical implementation of 15 mg ACZ doses as an adherence marker excipient in distinct cohorts taking ACZ for different “adherence” durations. We confirm that ACZ output did not change (accumulate) during 18–20 days of adherence, and developed and assessed urinary cutoffs as nonadherence indicators. We demonstrate that whereas an absolute con...

Research paper thumbnail of Miniaturized extraction method for analysis of synthetic opioids in urine by microextraction with packed sorbent and liquid chromatography—tandem mass spectrometry

Journal of Chromatography A, 2020

Synthetic opioids are responsible for numerous overdoses and fatalities worldwide. Currently, fen... more Synthetic opioids are responsible for numerous overdoses and fatalities worldwide. Currently, fentanyl and its analogs are also mixed with heroin, cocaine and methamphetamine, or sold as oxycodone, hydrocodone and alprazolam in counterfeit medications. Microextraction techniques became more frequent in analytical toxicology over the last decade. A method to simultaneously quantify nine synthetic opioids, fentanyl, sufentanil, alfentanil, acrylfentanyl, thiofentanyl, valerylfentanyl, furanylfentanyl, acetyl fentanyl and carfentanil, and two metabolites, norfentanyl and acetyl norfentanyl, in urine samples by microextraction with packed sorbent (MEPS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated. A multivariate optimization was performed to establish the number and speed (stroke) of draw-eject sample cycles and the extraction solvent. The best extraction condition was eight draw-eject sample cycles, with a velocity of 3.6 µL/sec and acetonitrile as elution solvent. Linearity was achieved between 1 to 100 ng/mL, with a limit of detection (LOD) of 0.1 ng/mL and limit of quantification (LOQ) of 1 ng/mL. Imprecision (% relative standard deviation) and bias (%) were less than 12.8% and 5.7%, respectively. The method had good specificity and selectivity when challenged with 10 different matrix sources and 36 pharmaceuticals and drugs of abuse at concentrations of 100 or 500 ng/mL. The method was successfully applied to authentic urine samples. MEPS was an efficient semi-automatic extraction technique, requiring small volumes of organic solvents (640 µL) and sample (200 µL). The cartridges can be cleaned and reused (average of 150 sample extractions/barrel inside and needle).

Research paper thumbnail of The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda

Drug and Alcohol Dependence, 2020

Research paper thumbnail of Measuring Within-Individual Cannabis Reduction in Clinical Trials: a Review of the Methodological Challenges

Current Addiction Reports, 2019

Research paper thumbnail of Prenatal exposure to tobacco and cannabis: Effects on autonomic and emotion regulation

Neurotoxicology and Teratology, 2018