Fiona J. Couper

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.

GHB and driving impairment.

Gamma hydroxybutyrate (GHB) was identified in the blood of 13 subjects arrested for impaired driving. GHB concentrations ranged from 26 to 155 mg/L (mean 87 mg/L, median 95 mg/L). In eight cases, GHB was the only drug detected, and signs of impairment were consistent with those of a CNS depressant, including erratic driving (weaving, swerving, ignoring road signs), confusion, incoherent speech, unresponsiveness, lack of balance, unsteady coordination, poor performances on field sobriety tests, and varying states of wakefulness. Given the ability of GHB to induce sleep and unconsciousness, it is evident from these cases that recreational use of the drug has the potential to impair a persons driving ability.

EXTRACTION OF PSYCHOTROPIC DRUGS FROM HUMAN SCALP HAIR

A comparison of techniques for the extraction of antidepressant and antipsychotic drugs in human scalp hair is described. Human scalp hair was obtained from cadavers known to be taking psychotropic drugs prior to their death. Following a washing step, hair was either solubilized in sodium hydroxide, or treated with dilute hydrochloric acid, methanol or subtilisin. Digests were treated with a solvent and the extracted drugs quantified by high performance liquid chromatography. The alkaline digestion procedure was found to be significantly more effective (P < 0.01) in recovering a range of antidepressant and antipsychotic drugs from hair than either the acidic, methanolic or enzymatic treatments.

Detection of antidepressant and antipsychotic drugs in postmortem human scalp hair.

The presence of therapeutic drugs in postmortem human scalp hair was investigated. Hair samples from 21 cadavers known to have taken antidepressant and antipsychotic drugs were solubilized in 1 M sodium hydroxide. Drugs were extracted using solvent extraction procedures and analyzed by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC). Antidepressant drugs detected were amitriptyline, dothiepin, doxepin, imipramine, trimipramine, and mianserin. Antipsychotic drugs detected were haloperidol, chlorpromazine and thioridazine. Concentrations of these drugs and their metabolites ranged from 1.3 to 242 ng/mg hair. Segmental analysis demonstrated that the drug concentrations detected were either consistent with the known dosing regime of the deceased, or were able to provide an indication of drug use within the last few months prior to death. This study reinforces the potential of hair as a useful tissue in forensic investigations, in establishing a history of past exposures to therapeutic drugs.

Gas chromatographic-mass spectrometric determination of ß2-agonists in postmortem blood: application in forensic medicine

A solid-phase extraction procedure is described for the simultaneous determination of terbutaline, salbutamol and fenoterol in human postmortem whole blood, using gas chromatography-electron impact mass spectrometry. The limit of quantitation in 1 ml of blood was 1 ng/ml for all analytes. A linear response was observed over the concentration ranges tested, covering both low and high concentrations of each drug. The recoveries in postmortem blood were: terbutaline, 88%; salbutamol, 86%; fenoterol, 92%; orciprenaline (internal standard), 86%. Coefficients of variations for both intra-assay precision and inter-assay reproducibility ranged between 2.2 and 13.0% for all analytes. This method is sensitive and selective, and has been applied successfully to over 60 postmortem blood specimens.

Postmortem stability and interpretation of beta 2-agonist concentrations.

This paper describes a series of stability and redistribution studies aimed at understanding the presence and significance of beta 2-agonists in asthma deaths. Salbutamol and terbutaline were shown to be stable in postmortem blood at 23 degrees C for 1 week, 4 degrees C for 6 months and -20 degrees C for 1 to 2 years. However, fenoterol was shown to degrade at 23 degrees C (83% loss), 4 degrees C (93% loss) and -20 degrees C (66% loss) over the same time. Salbutamol concentrations detected in blood taken at the time of body admission to the mortuary were not significantly different from the concentrations detected in blood taken from the same cases at the time of autopsy (45 h later). This suggests that significant postmortem redistribution of salbutamol is unlikely to occur during this period. Postmortem blood concentrations of at least salbutamol are likely to reflect the concentration of these drugs in the body at the time of death.

Two Fatal Intoxications Involving 3-Methoxyphencyclidine

3- and 4-methoxyphencyclidine (3-MeO-PCP, 4-MeO-PCP), structural analogs of phencyclidine (PCP), were among the first legal PCP alternatives to show up on the novel psychoactive substances (NPS) market in Europe in the 2000s. Their structural similarities to PCP and ketamine likely contribute to their demonstrated dissociative anesthetic effects. Limited information exists in the literature about toxic and lethal concentrations of these drugs in biological samples. This case report presents the first two death cases in Washington State in which 3-MeO-PCP was identified. Alkaline drug screen analysis by gas chromatography-mass spectrometry (GC-MS) revealed a peak with a retention time similar to PCP and base peak of m/z 230. Certified reference materials for 3-and 4-MeO-PCP were obtained and the isomers were able to be distinguished based on different retention times and mass spectra. A quantitative GC-MS method was developed and validated for casework, utilizing a dynamic range of 10-1,000 ng/mL and a limit of detection of 1 ng/mL. Postmortem (peripheral/central) blood samples were analyzed using this method and the resulting concentrations were 0.63 and 3.2 mg/L of 3-MeO-PCP. Methamphetamine (0.11 mg/L) was additionally detected in the blood of one of the decedents; while the second decedent was additionally positive for ethanol (0.047 g/100 mL), bupropion (1.8 mg/L), delorazepam, paroxetine and mitragynine. The results presented in this case report are higher than previously reported concentrations in fatal cases, but the presence of polysubstance abuse is consistent with previously reported NPS intoxications. Both of these individuals were in drug rehabilitation facilities prior to their deaths; however, users continue to be drawn to 3-MeO-PCP due to its dissociative effects and its accessibility on the internet.