Barry K. Logan

CAUSE AND MANNER OF DEATH IN FATALITIES INVOLVING METHAMPHETAMINE

We reviewed a series of deaths in which methamphetamine was detected in the decedents blood. Analysis of postmortem whole blood was performed by gas chromatography/mass spectrometry with a limit of quantitation of 0.05 mg/L. Methamphetamine was detected in 146 cases; 52 were drug caused, i.e., a death in which the direct toxic effects of the drug caused or contributed to the death, 92 were classified as drug related, i.e., a death in which the drug was demonstrated in the blood, but did not directly cause death. A large proportion of the deaths resulted from homicidal (27%) or suicidal (15%) violence. An examination of methamphetamine concentrations in drug related deaths (n = 92), suggests that the range of concentrations in the recreational abusing population is substantial (0.05-9.30 mg/L) but with a median concentration of 0.42 mg/L, and with 90% of that population having concentrations less than 2.20 mg/L. There was substantial overlap in methamphetamine concentration between drug related deaths and drug caused deaths, although the highest concentrations were seen in the unintentional (accidental or undetermined) drug caused deaths. Methamphetamine related traffic deaths (n = 17) showed patterns of driving behavior consistent with reports elsewhere, and showed blood methamphetamine concentrations ranging from 0.05-2.60 mg/L (median 0.35 mg/L). The data show that most methamphetamine deaths occur with blood concentrations greater than 0.5 mg/L, but can occur with levels as low as 0.05 mg/L, though usually in conjunction with other drugs or significant natural disease. Neither apparently toxic nor therapeutic concentrations should be used in isolation to establish conclusively whether a death was caused by methamphetamine; proper classification of deaths involving methamphetamine requires complete death investigation, including investigation of the scene and circumstances of death, and a complete autopsy.

Methamphetamine and driving impairment.

Following a review of the effects of methamphetamine on human performance, actual driving and behavior were evaluated in 28 cases in which drivers arrested or killed in traffic accidents had tested positive for methamphetamine. The circumstances surrounding the arrest or accident were examined, together with any observations by the arresting officer regarding behavioral irregularities. The investigators also made a determination of culpability. Most of the arrests resulted from accidents in which the driver was determined to be culpable. Typical driving behaviors included drifting out of the lane of travel, erratic driving, weaving, speeding, drifting off the road, and high speed collisions. Behavioral manifestations of methamphetamine use in arrestees included rapid or confused speech, rapid pulse, agitation, paranoia, dilated pupils, violet or aggressive attitude. Combined alcohol and methamphetamine use was uncommon, however use of marijuana was evident in about one third of the cases. In addition to impairing judgment and increasing risk taking, the effects of withdrawal from methamphetamine use including fatigue, hypersomnnolence, and depression are likely contributors to many of these accidents. A consideration of the literature and the cases discussed here, leads to the conclusion that methamphetamine at any concentration is likely to produce symptoms that are inconsistent with safe driving.

Identification of Synthetic Cannabinoids in Herbal Incense Blends in the United States

Abstract:  Synthetic cannabinoid agonists are chemically diverse with multiple analogs gaining popularity as drugs of abuse. We report on the use of thin layer chromatography, gas chromatography mass spectrometry, high‐performance liquid chromatography, and liquid chromatography time of flight mass spectrometry for the identification and quantitation of these pharmacologically active chemicals in street drug dosage forms. Using these approaches, we have identified the synthetic cannabinoids JWH‐018, JWH‐019, JWH‐073, JWH‐081, JWH‐200, JWH‐210, JWH‐250, CP47,497 (C=8) (cannabicyclohexanol), RCS‐4, RCS‐8, AM‐2201, and AM‐694 in various commercially available products. Other noncannabinoid drugs including mitragynine have also been detected. Typical concentrations of drug in the materials are in the range 5–20 mg/g, or 0.5–2% by weight for each compound, although many products contained more than one drug.

Postmortem Forensic Toxicology of Selective Serotonin Reuptake Inhibitors: A Review of Pharmacology and Report of 168 Cases

This paper reviews the complex pharmacology of the new class of antidepressant medications exhibiting selective inhibition of serotonin reuptake. The four selective serotonin reuptake inhibitors (SSRIs) considered--fluoxetine, fluvoxamine, sertraline and paroxetine--can result in toxicity and death through contributing to serotonergic excess resulting in serotonin syndrome, inhibiting the metabolism of other centrally acting drugs, leading to accumulation of toxic concentrations, and exerting complex vasoactive effects on the vascular smooth muscle. This latter feature is of particular concern in patients with preexisting heart disease. An analytical method involving isolation of the drugs by liquid/liquid extraction at alkaline pH into n-butyl chloride, and analysis by gas chromatography/mass spectrometry (GC/MS) is described, together with some of its limitations. Toxicologic and cause and manner of death data were examined in 60 deaths involving fluoxetine, 5 involving fluvoxamine, 75 involving sertraline, and 28 involving paroxetine. Deaths involving drug toxicity were generally a result of ingestion of multiple drugs, and in only a small number of the cases was death attributed principally to the SSRI involved. The potential for drug interactions between members of this class of drugs is discussed as well as their metabolites and a variety of other therapeutic and abused drugs which can contribute to their toxicity. In the absence of other risk factors, the lowest concentrations determined to have resulted in death were 0.63 mg/L for fluoxetine, 0.4 mg/L for paroxetine, and 1.5 mg/L for sertraline. We had insufficient data to make even this crude assessment for fluvoxamine. Drug-induced elevation of serotonin concentrations may be a significant risk factor for patients with atherosclerotic cardiovascular disease (ASCVD). Other factors including preexisting disease and the presence of other drugs and their pharmacology need to be carefully considered before determining the appropriate cause and manner of death in these cases.

Methadone Levels in Breast Milk

Two case reports of breastfeeding mothers on high doses of methadone and a literature review reveal that minimal transmission of methadone into breast milk occurs regardless of the mothers methadone dose. The current American Academy of Pediatrics recommendations that only women in drug treatment programs on less than 20 mg/day of methadone be advised to breastfeed should be reconsidered.

Postmortem Distribution and Redistribution of Morphine in Man

This study evaluated both site dependent differences and time dependent changes in postmortem morphine concentrations in man. In 32 deaths involving morphine, left ventricular blood, femoral blood, and cisternal cerebrospinal fluid, were collected as soon after death as possible (T1), and collected again together with iliac blood at the time of autopsy (T2). Samples were analyzed for morphine by radioimmunoassay. No evidence was found for changes in morphine concentration with respect to time at either central or peripheral sites, or in the cerebrospinal fluid. Ventricular blood morphine concentrations were however consistently higher than those in the peripheral compartment, represented by either femoral or iliac blood. This was particularly true when the ventricular morphine concentration exceeded 0.300 mg/L. At peripheral sites, femoral and iliac blood morphine concentrations were well correlated with each other, making either an appropriate site for collection of peripheral blood for toxicological testing.

Validation of a Novel Immunoassay for the Detection of Synthetic Cannabinoids and Metabolites in Urine Specimens

Synthetic cannabinoid drugs do not cross react on traditional marijuana immunoassay tests, preventing their use in large scale drug screening programs. This paper describes the validation and performance characteristics of two enzyme linked immunosorbent assays designed to detect the use of two common synthetic cannabinoids in urine, JWH-018 and JWH-250. The JWH-018 assay has significant cross-reactivity with several synthetic cannabinoids and their metabolites, whereas the JWH-250 assay has limited cross-reactivity. The assays are calibrated at 5 ng/mL with the 5-OH metabolite of JWH-018 and the 4-OH metabolite of JWH-250. The method was validated with 114 urine samples for JHW-018 and 84 urine samples for JWH-250 and confirmed by using liquid chromatography tandem mass spectrometry, which tests for metabolites of JWH-018, JWH-019, JWH-073, JWH-250 and AM-2201. The accuracy was determined to be 98% with greater than 95% sensitivity and specificity for both assays.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) and driving impairment

3,4-Methylenedioxymethamphetamine, or MDMA, is increasing in popularity in the United States as a drug of abuse. It has stimulant and empathogenic mood altering properties with the potential to affect psychomotor skills and impact driving. This report reviews the literature relating to the relevant psychomotor effects of the drug, the relationship between dose and blood concentrations, and studies and case reports on specific effects of the drug on driving. The latter reports include both laboratory driving simulator studies and anecdotal reports, and case series. We also report details of eighteen cases of apparent MDMA impaired driving, including six drivers whose blood tested positive for MDMA alone. Most subjects displayed muscle twitching and body tremors, dilated pupils, slow pupillary reaction to light, elevated pulse and blood pressure, lack of balance and coordination, and most were perspiring profusely. Five of the six subjects were given field sobriety tests (one leg stand, walk and turn test), and all five performed poorly. There was no clear correlation between the blood concentration of MDMA and the specific demeanor of the subject. These findings are consistent with other reports, and lead to the conclusion that MDMA use is not consistent with safe driving, and that impairment of various types may persist for a considerable time after last use.

Endogenous ethanol 'auto-brewery syndrome' as a drunk-driving defence challenge.

The concentration of ethanol in blood, breath or urine constitutes important evidence for prosecuting drunk drivers. For various reasons, the reliability of the results of forensic alcohol analysis are often challenged by the defence. One such argument for acquittal concerns the notion that alcohol could be produced naturally in the body, hence the term ‘auto-brewery’ syndrome. Although yeasts such as Candida albicans readily produce ethanol in-vitro, whether this happens to any measurable extent in healthy ambulatory subjects is an open question. Over the years, many determinations of endogenous ethanol have been made, and in a few rare instances (Japanese subjects with very serious yeast infections) an abnormally high ethanol concentration (<80 mg/dl) has been reported. In these atypical individuals, endogenous ethanol appeared to have been produced after they had eaten carbohydrate-rich foods. A particular genetic polymorphism resulting in reduced activity of enzymes involved in hepatic metabolism of ethanol and a negligible first-pass metabolism might explain ethnic differences in rates of endogenous ethanol production and clearance. Other reports of finding abnormally high concentrations of ethanol in body fluids from ostensibly healthy subjects suffer from deficiencies in study design and lack suitable control experiments or used non-specific analytical methods. With reliable gas chromatographic methods of analysis, the concentrations of endogenous ethanol in peripheral venous blood of healthy individuals, as well as those suffering from various metabolic disorders (diabetes, hepatitis, cirrhosis) ranged from 0–0.08 mg/dl. These concentrations are far too low to have any forensic or medical significance. The notion that a motorists state of intoxication was caused by endogenously produced ethanol lacks merit.

Carisoprodol, meprobamate, and driving impairment

This paper considers the pharmacology of the centrally acting muscle relaxant carisoprodol, and its metabolite meprobamate, which is also administered as an anxiolytic in its own right. Literature implicating these drugs in impaired driving is also reviewed. A series of 104 incidents in which these drugs were detected in the blood of drivers involved in accidents or arrested for impaired driving was considered, with respect to the analytical toxicology results, patterns of drug use in these subjects, the driving behaviors exhibited, and the symptoms observed in the drivers. Symptomatology and driving impairment were consistent with other CNS depressants, most notably alcohol. Reported driving behaviors included erratic lane travel, weaving, driving slowly, swerving, stopping in traffic, and hitting parked cars and other stationary objects. Drivers on contact by the police displayed poor balance and coordination, horizontal gaze nystagmus, bloodshot eyes, unsteadiness, slurred speech, slow responses, tendency to doze off or fall asleep, difficulty standing, walking or exiting their vehicles, and disorientation. Many of these cases had alcohol or other centrally acting drugs present also, making difficult the attribution of the documented impairment specifically to carisoprodol and meprobamate. In 21 cases, however, no other drugs were detected, and similar symptoms were present. Impairment appeared to be possible at any concentration of these two drugs; however, the most severe driving impairment and most overt symptoms of intoxication were noted when the combined concentration exceeded 10 mg/L, a level still within the normal therapeutic range.