Manfred R. Moeller

High-Potency Marijuana Impairs Executive Function and Inhibitory Motor Control

Human performance studies have usually relied on low-potency marijuana (4% THC) for determining THC-induced impairment. The present study was designed to assess the effects of high-potency marijuana (13% THC) on human performance. In all, 20 recreational users of marijuana participated in a double-blind, placebo controlled, three way cross-over study. The treatments consisted of single doses of 0, 250, and 500 μg/kg THC. Performance tests were conducted at regular intervals between 15 min and 6 h postsmoking and included measures of motor control (Critical tracking task), executive function (Tower of London) motor impulsivity (Stop signal task), and risk taking (Iowa gambling task). THC significantly impaired performance in the Critical tracking task and decreased the number of correct decisions in the Tower of London task. In addition, THC significantly increased stop reaction time and the proportions of commission and omission errors in the Stop signal task. THC-induced impairments lasted up to 6 h postsmoking as indicated by the absence of a THC × Time after smoking interaction. Effect sizes for performance impairments produced by THC 250 μg/kg were relatively low but generally increased by a factor of two in case of THC 500 μg/kg. These data suggest that high potency marijuana consistently impairs executive function and motor control. Use of higher doses of THC in controlled studies may offer a reliable indication of THC induced impairment as compared to lower doses of THC that have traditionally been used in performance studies.

Neurocognitive performance during acute THC intoxication in heavy and occasional cannabis users

Abstract Performance impairment during Δ9-tetrahydrocannabinol (THC) intoxication has been well described in occasional cannabis users. It is less clear whether tolerance develops to the impairing effects of THC in heavy users of cannabis. The aim of the present study was to assess neurocognitive performance during acute THC intoxication in occasional and heavy users. Twenty-four subjects (12 occasional cannabis users and 12 heavy cannabis users) participated in a double-blind, placebo-controlled, two-way mixed model design. Both groups received single doses of THC placebo and 500 μg/kg THC by smoking. Performance tests were conducted at regular intervals between 0 and 8 h after smoking, and included measures of perceptual motor control (critical tracking task), dual task processing (divided attention task), motor inhibition (stop signal task) and cognition (Tower of London). THC significantly impaired performance of occasional cannabis users on critical tracking, divided attention and the stop signal task. THC did not affect the performance of heavy cannabis users except in the stop signal task, i.e. stop reaction time increased, particularly at high THC concentrations. Group comparisons of overall performance in occasional and heavy users did not reveal any persistent performance differences due to residual THC in heavy users. These data indicate that cannabis use history strongly determines the behavioural response to single doses of THC.

Relationship Between Oral Fluid and Blood Concentrations of Drugs of Abuse in Drivers Suspected of Driving Under the Influence of Drugs

In recent years, the interest in the use of oral fluid as a biological matrix has increased significantly, particularly for detecting driving under the influence of drugs (DUID). In this study, the relationship between the oral fluid and the blood concentrations of drugs of abuse in drivers suspected of DUID is discussed. Blood and oral fluid samples were collected from drivers suspected of DUID or stopped during random controls by the police in Belgium, Germany, Finland, and Norway for the ROSITA-2 project. The blood samples were analyzed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), sometimes preceded by immunoassay screening of blood or urine samples. The oral fluid samples were analyzed by GC-MS or LC-MS(/MS). Scatter plots and trend lines of the blood and oral fluid concentrations and the median, mean, range, and SD of the oral fluid to blood (OF:B) ratios were calculated for amphetamines, benzodiazepines, cocaine, opiates, and ▵9-2 tetrahydrocannabinol. The ratios found in this study were comparable with those that were published previously, but the range was wider. The OF:B ratios of basic drugs such as amphetamines, cocaine, and opiates were >1 [amphetamine: median (range) 13 (0.5-182), methylenedioxyamphetamine: 4 (1-15), methylenedioxymethamphetamine: 6 (0.9-88), methamphetamine: 5 (2-23), cocaine: 22 (4-119), benzoylecgonine: 1 (0.2-11), morphine: 2 (0.8-6), and codeine: 10 (0.8-39)]. The ratios for benzodiazepines were very low, as could be expected as they are highly protein bound and weakly acidic, leading to low oral fluid concentrations [diazepam: 0.02 (0.01-0.15), nordiazepam: 0.04 (0.01-0.23), oxazepam: 0.05 (0.03-0.14), and temazepam: 0.1 (0.06-0.54)]. For tetrahydrocannabinol, an OF:B ratio of 15 was found (range 0.01-569). In this study, the time of last administration, the dose, and the route of administration were unknown. Nevertheless, the data reflect the variability of the OF:B ratios in drivers thought to be under the influence of drugs. The wide range of the ratios, however, does not allow reliable calculation of the blood concentrations from oral fluid concentrations.

Drugs of abuse monitoring in blood for control of driving under the influence of drugs

Driving under the influence of drugs is an issue of growing concern in the industrialized countries as a risk and a cause for road accidents. In forensic toxicology, the increasing number of samples for determination of drugs in blood is mainly due to zero-tolerance laws in several countries and well-trained police officers who can better recognize drivers under the influence of drugs of abuse. This review describes procedures for detection of the following drugs of abuse in whole blood, plasma, and serum: amphetamine, methamphetamine, 3,4-methylenedioxy methamphetamine (MDMA), N-ethyl-3, 4-methylenedioxyamphetamine (MDEA), 3,4-methylenedioxyamphetamine (MDA), cannabinoids (delta-9-tetrahydrocannabinol [THC], 11-hydroxy-delta-9-THC, 11-nor-9-carboxy-delta-9-THC), cocaine, benzoylecgonine, ecgonine methyl ester, cocaethylene, the opiates (heroin, 6-monoacetylmorphine, morphine, or codeine), and methadone as well as gamma-hydroxybutyric acid (GHB), lysergic acid diethylamide (LSD), phencyclidine (PCP), and psilocybin/psilocin. For many of the analytes, sensitive immunologic methods for screening are available. Gas chromatography-mass spectrometry (GC-MS) is still the state-of-the-art method for confirmatory analysis or for screening and confirmation in one step. Liquid chromatography-mass spectrometry (LC-MS) procedures for such purposes are also included in this review. Basic data about the biosample assayed, internal standard, workup, GC or LC column and mobile phase, detection mode, reference data, and validation data of each procedure are summarized in two tables.

Biochemical approach on the conservation of drug molecules during hair fiber formation

A biochemical concept for the endogenous incorporation of drug molecules into growing hair is presented. It is based on the principles of transport across biomembranes, on the principles of biotransformation and drug melanin affinity. The approach gives explanations for current observations in hair analysis, which up to date have not been understood sufficiently. Phenomena such as the ratio of parent drug to metabolite in hair, the dependence of incorporation on the physico-chemical properties of the drug, the independence of drug incorporation on active melanogenesis (incorporation into non-pigmented hair) as well as the dependence of drug content on hair pigmentation are elucidated.

Drug detection in hair by chromatographic procedures

This article reviews the analysis of 31 drugs and drug metabolites in human hair by thin-layer chromatography, high-performance liquid chromatography, gas chromatography, gas chromatography-mass spectrometry and mass spectrometry. The most important detection method after chromatographic separation of the components is the mass spectrometry because of its sensitivity and specificity. Washing steps to exclude external contamination, extraction, derivatization, stationary phases, detection modes and detection limits of the mass spectrometric and gas chromatographic-mass spectrometric procedures are presented in five tables. Additionally, a method for a gas chromatographic-mass spectrometric screening procedure is presented.

Enantioselective separation of methadone and its main metabolite in human hair by liquid chromatography/ion spray-mass spectrometry.

Optical isomers exhibit significant differences in their affinities for receptor sites, biotransformation and binding to serum and tissue proteins. Methadone has been used for the substitution of heroin addicts since 1964. The racemic form is used, i.e., a mixture of the biologically active R-form and the practically inactive S-form. To investigate methadone distribution, a chiral separation of the isomers was developed in human hair samples. The method involves decontamination of hair with water and acetone, pulverization in a ball mill, enzymatic hydrolysis in presence of deuterated internal standards, solid-phase extraction, and liquid chromatography/ion spray-mass spectrometry. Enantioselective separation of methadone and its main metabolite, EDDP, was obtained using an alpha1-acid glycoprotein column (100 by 4 mm ID). In all nine specimens obtained from subjects under racemic methadone treatment in a detoxification center, R- and S-enantiomers of methadone and EDDP were identified with the following concentrations: 2.58-10.22, 1.89-9.53, 0.42-1.73, and 0.40-2.10 ng/mg for R-methadone, S-methadone, R-EDDP, and S-EDDP, respectively. Results are suggestive of a predominance of the Renantiomer of methadone in human hair.

Practical aspects of roadside tests for administrative traffic offences in Germany

In the context of the European project ROSITA, the Institut of Legal Medicine Homburg/Saar has co-operated with the Saarland traffic police in order to assess different roadside drug tests for their functionality and reliability in traffic controls, and for their analytical force of evidence. In 254 cases within the time period from June 1999 to December 1999, police officers performed a (voluntary) roadside drug testing in saliva/sweat, or urine, to confirm or refute their initial suspicion that a driver had used drugs. Whereas in 45 cases the tests gave negative results (which were confirmed by lab urinalysis), in 209 cases the police officers ordered blood samples after a positive outcome of the tests. In 203 of the 209 positive cases, the results could be confirmed by GC/MS analysis. Regarding the prevalence of used drugs, a single consumption was found in 156 cases (113 cannabis, 38 amphetamines/methamphetamines, three opiates, two cocaine), and a consumption of two drugs was found in 44 cases (34 cannabis+amphetamines/methamphetamines, five cannabis+opiates, three cannabis + cocaine, two cocaine+amphetamines/methamphetamines). In three cases, multi-consumption was found. In six cases, the performed tests gave an incorrect prediction to the police officer at the roadside.The roadside tests gave 97.6% correct assistance to the police officers in the right direction (79.9% correct positive predictions and 17.7% correct negative predictions). As a consequence, the performed tests can be seen as a positive and needful tool for the police to get an immediate response to their initial suspicion and to take the right steps concerning a following legal action.

Zum Suchtmittelnachweis in Haaren

An attempt is made to explain the incorpora- tion of drug molecules during hair fiber formation using the classical concepts of drug absorption anda modero bi- ological approach on the permeability of cell membranes. The principles of biological transport across membranes are applied to the matrix cells and the melanocytes in the hair bulb. In addition to the physicochemical parameters of the drug substances such as molecular weight, molecu- lar geometry, degree of ionization, octanol/water partition coefficient, plasma protein binding, drug-melanin affinity, and acid/base status of the functional groups within the molecule, drug incorporation is thought to be limited by the surface area and the residence time in the hair bulb. The ratio of high parent drug to low metabolite concentra- tion, which is currently observed in hair, is speculated to be a result of biotransforrnation in the follicle cells. Drug incorporation into non-pigmented hair as well as the de- pendency of drug concentration on hair pigmentation can be explained. The fate of the drug substances during cell differentiation and keratinization is discussed. From the biochemistry it is considered that lipids (cell membrane complex), melanin (melanin granules), and proteins (in- termediate filaments; intermediate filament associated pro- teins) are the main sources of drug molecules in the kera- tinized hair fibers.An attempt is made to explain the incorporation of drug molecules during hair fiber formation using the classical concepts of drug absorption and a modern biological approach on the permeability of cell membranes. The principles of biological transport across membranes are applied to the matrix cells and the melanocytes in the hair bulb. In addition to the physicochemical parameters of the drug substances such as molecular weight, molecular geometry, degree of ionization, octanol/water partition coefficient, plasma protein binding, drug-melanin affinity, and acid/base status of the functional groups within the molecule, drug incorporation is thought to be limited by the surface area and the residence time in the hair bulb. The ratio of high parent drug to low metabolite concentration, which is currently observed in hair, is speculated to be a result of biotransformation in the follicle cells. Drug incorporation into non-pigmented hair as well as the dependency of drug concentration on hair pigmentation can be explained. The fate of the drug substances during cell differentiation and keratinization is discussed. From the biochemistry it is considered that lipids (cell membrane complex), melanin (melanin granules), and proteins (intermediate filaments; intermediate filament associated proteins) are the main sources of drug molecules in the keratinized hair fibers.ZusammenfassungEs wird ein Konzept zum Einbau organischer Substanzen in das wachsende Haar vorgestellt. Es basiert auf den Regeln des Stofftransportes durch Zellmembranen, den Prinzipien des Fremdstoffmetabolismus und der bekannten Melaninaffinität vieler Substanzen. Die interdisziplinäre Betrachtung und die Anwendung biochemischer Mechanismen auf die Vorgänge und Zellpopulationen im Haarfollikel kann die Konservierung der organischen Substanzen infolge der Keratinisierungsprozesse und einige bisher noch nicht völlig verstandene Phänomene, wie das Konzentrationsverhältnis von Muttersubstanz zu Metaboliten im Haar, erklären. Nachvollziehbar wird auch, daß der Einbau von Substanzen einerseits unabhängig von einer aktiven Melanogenese, d.h. in nicht pigmentierte Haare stattfindet, andererseits eine Abhängigkeit des Analysenergebnisses von der Haarpigmentierung für Substanzen mit hoher Melaninaffinität besteht. Es läßt sich aus den Betrachtungen ableiten, daß die Hauptlokalisation der Drogenmoleküle im keratinisierten Haar die Haarlipide (Zellmembrankomplex), das Haarpigment (Melaningranula) und die Haarproteine (Intermediat Filamente [IF], Intermediat Filament-assozierte Proteine [IFAPs]) darstellen.

Hair analysis as evidence in forensic cases.

The analysis of hair for drugs of abuse is a powerful tool useful in answering questions that cannot be solved by the detection of drugs in body fluids, e.g., blood, urine, or saliva. The most frequent forensic investigations occur in cases where narcotics laws are offended and in questions of criminal responsibility where the chronic use of a drug is an issue. In the list of drugs of abuse, heroin, cocaine, amphetamine, and cannabis are the drugs of abuse that are most frequently involved in judicial inquiries.