**3. Alcohol, drugs and driving**

The studies of "Man-Machine Interaction" [7], evaluating the complex of actions and abilities required to drive motor vehicles and complex machinery (such as industrial), demonstrate that alcohol, drugs and medication influence the psychosensorial and psychomotor functions underlying such skills.

The effects of acute intake of **ethyl alcohol** vary depending on the levels of ethanolemia (in mg%mL o g/L) and the characteristics of the subject. Alcohol can induce sedation and reduction of anxiety, dyslalia, ataxia, impaired judgement and disinhibition. Alcohol has psychobehavioural effects linearly correlated to its blood concentration. The 50 mg%mL limit, fixed by most driving codes as the limit for drunk driving, is not predictive of the disabling effects of lower concentrations, more evident in the adolescent and elderly population. In any case, the multiplication of risk by 3, 10 and 40 times applies when haematic concentrations exceed 80, 100 and 150 mg%mL, respectively. Driving with levels greater than 150 mg%mL substan‐ tiate the identification of alcohol abuse or dependency problems, in need of social-rehabilita‐ tive intervention. In Table 1 is a summary of the dysfunctions correlating to values of blood alcohol concentration (BAC) derived from clinical observation and studies on man-machine interaction.

Knowledge of the above described effects and the observation in a real or simulated driving test, allow for the following conclusions. Alcohol consumption determines a deterioration in one's driving ability through an increase in speed, loss of awareness, impaired visual function and attention, wavering about the lane markings, slowing down of reaction time for "breaking and steering", overestimation of "collision" time, inadequate risk assessment [8,9]. Scarce experience, age, alcohol tolerance are factors enhancing alcohol related driving incapacity.


**Table 1.** Values of BAC and correlation with driving dysfunctions

present in the victim's body some time before death. The physiopathological effects of the

The laboratory plays a crucial role in the forensic toxicological diagnostic when a correct methodology is adopted in sampling procedures and the choice of specimen to be analysed, and when interpretation of the results is well integrated with the data acquired through other

Once the ascertainment is completed in all its stages, an evaluation phase is undertaken, in which the results of different types of tests must be comparatively and critically evaluated.

Identification of intoxication as a cause of medico-legal relevance can emerge in terms of certainty or probability, which is in turn distinguished in statistical and logical probability.

In toxicology there are not often general scientific laws, of universal or statistical epidemio‐ logical coverage, which make it possible to verify or rule out exposure to toxic substances as a cause of medico- legal relevance. It follows that one must usually have recourse to the process of rational credibility, according to the best science and experience, on the basis of what is known regarding the ethio-pathogenesis of disease from toxic origin. In the appendix, the characteristics of the most common drugs of abuse, responsible of acute or chronic intoxication, are shortly summarized according to The National Institute of Drugs of Abuse (NIDA).

The studies of "Man-Machine Interaction" [7], evaluating the complex of actions and abilities required to drive motor vehicles and complex machinery (such as industrial), demonstrate that alcohol, drugs and medication influence the psychosensorial and psychomotor functions

The effects of acute intake of **ethyl alcohol** vary depending on the levels of ethanolemia (in mg%mL o g/L) and the characteristics of the subject. Alcohol can induce sedation and reduction of anxiety, dyslalia, ataxia, impaired judgement and disinhibition. Alcohol has psychobehavioural effects linearly correlated to its blood concentration. The 50 mg%mL limit, fixed by most driving codes as the limit for drunk driving, is not predictive of the disabling effects of lower concentrations, more evident in the adolescent and elderly population. In any case, the multiplication of risk by 3, 10 and 40 times applies when haematic concentrations exceed 80, 100 and 150 mg%mL, respectively. Driving with levels greater than 150 mg%mL substan‐ tiate the identification of alcohol abuse or dependency problems, in need of social-rehabilita‐ tive intervention. In Table 1 is a summary of the dysfunctions correlating to values of blood alcohol concentration (BAC) derived from clinical observation and studies on man-machine

Knowledge of the above described effects and the observation in a real or simulated driving test, allow for the following conclusions. Alcohol consumption determines a deterioration in one's driving ability through an increase in speed, loss of awareness, impaired visual function

majority of the xenobiotics only correlates, in fact, with their blood concentration.

types of research.

90 Toxicology Studies - Cells, Drugs and Environment

**3. Alcohol, drugs and driving**

underlying such skills.

interaction.

The central nervous system is affected not only by the acute effects of ethanol abuse, but also from chronic intake. A significant percentage of alcohol dependents are affected by dementia, cerebellar degeneration, peripheral miopathies and neuropathies.

Incapacity to drive caused by *Cannabis indica* (marijuana and hashish), varies according to the dose of active ingredient taken, not excluding the accidental consumer. Alterations of per‐ formance are reported for values of tetrahydrocannabinol (THC, the active principle of Cannabis) comprised between 2 and 5 ng/ml [10]. THC leads to an increase in systolic pressure and cardiac frequency, conjunctival hyperemia, difficulty with nocturnal vision and focusing on objects, above all if in motion, reduction in awareness, distortions of space and time, delayed reactions to stimuli, anxiety, paranoia, panic attacks, motor coordination deficit and impaired judgement with a greater propensity for "risk taking" [11]. These effects, especially expressive with speed and "wavering" of the car (as demonstrated by real driving tests), are accentuated by and also affect reaction times when cannabis is consumed in combination with alcohol [8], as well as together with other psychoactive substances. The effects of cannabinoids are also found in chronic consumers in the long term.

All **hallucinogens***,* of natural origin (mescaline, psilocine, psilocybine, etc.) or of synthesis (LSD, derivatives and analogues) induce driving incapacity, seriously altering all the sensitive, neurocognitive, and psychomotor functions, at any dose, either in a state of tolerance or intolerance. The hallucinogenic effects, which start from 15 minutes to 1 hour after ingestion, determine the increase of arterial pressure and of body temperature, as well as spatial-temporal distortion and depersonalisation, often leading to suicide attempts.

**Cocaine** and **amphetamines** are the most prevalent disabling psycho-stimulants, which, though causing a "HIGH" stage and initial improvement of certain psycho-motory functions (reaction time, attention, awareness), cause an incapacity by altering risk perception [12,13]. The initial stimulating effects are soon substituted by tremors, hypertension, tachycardia and, in the case of amphetamines, increase in body temperature and manifestation of epileptic convulsions. In the "DOWN" phase, debilitating effects follow such as depression, irritability, fatigue and anxiety attacks. The down phase can occur a early as 45 minutes after ingestion and has a duration of 2-4 days. As for amphetamine derivatives (e.g. ecstasy) physical and behavioural effects manifest after just a few minutes of ingestion, and protract up to six hours. Such effects, due to a generalized stimulation of the central nervous system, include: euphoria, hyperexcitability, nervousness, tachycardia, insomnia, anorexia, bruxism and mydriasis. Paradoxically, such effects are accompanied by a sense of wellbeing and relaxation and some ameliorative psychological effects. Among the chronic effects are deficits in cognitive functions (memory loss, difficulty concentrating and learning) and psychotic flashbacks. For both hallucinogens and psycho-stimulants drugs, studies of man-machine interaction demonstrate: an increase in dynamic variations of the motor vehicle, both in a lateral and longitudinal (waving) direction; maintenance of high speed; notable reduction of safety distances; reduced reaction to sound and visual stimuli (mydriasis). The above-mentioned effects, indicators of a considerable risk of road crashes and accidents [14], are accentuated or favoured by the combined intake of ethylic alcohol or the increase in drug dose (lateral undulations, increase in speed and reaction times).

The role of natural **opiates**, *Methadone* and *Buprenorphine* in the determination of road accidents is still debated. The verified effects on the incapacity to drive correlate to mood changes, reduced motor coordination, drowsiness, slower psychomotor coordination and pupillary constriction. Withdrawal symptoms and frequent association with other psychoactive substances take on considerable importance, particularly with ethyl alcohol. For some authors Methadone Maintenance Treatment is thought to impede capacity to drive, until psychic stabilisation (> 1 year) and secure absence of the co-use of other psychoactive substances. Buprenorphine in healthy subjects increases reaction time in a laboratory test but not in a simulation driving test.

Studies that have evaluated all medications employed in heroine dependence therapy have shown that the parameters of competence (deviation from the lateral standard position, speed and capacity to steer round a bend, reaction to stimuli), do not present a difference in treated patients *vs* controls, except in the case of combined intake of ethylic alcohol [15].

**Gamma hydroxybutyrate** (GHB), a natural constituent of diverse systems and apparatus of the human organism, also a drug used in anaesthesiology therapy and in the treatment of alcohol dependence, is the object of abuse for its euphoric, sedative and anabolic effects. Other effects deriving from GHB intake include: disorientation, slowness to react, agitation, inability to focus attention, impaired coordination and balance, tremors, drowsiness, unconsciousness. Given the capacity of GHB to induce sedation, the possibility of determining incapacity to drive motor vehicles becomes evident. It produces collateral effects characterized by nausea, vomiting, drowsiness, vertigo, bradycardia and respiratory depression, coma. Association with alcohol exponentially increases the above described effects [16].

All **hallucinogens***,* of natural origin (mescaline, psilocine, psilocybine, etc.) or of synthesis (LSD, derivatives and analogues) induce driving incapacity, seriously altering all the sensitive, neurocognitive, and psychomotor functions, at any dose, either in a state of tolerance or intolerance. The hallucinogenic effects, which start from 15 minutes to 1 hour after ingestion, determine the increase of arterial pressure and of body temperature, as well as spatial-temporal

**Cocaine** and **amphetamines** are the most prevalent disabling psycho-stimulants, which, though causing a "HIGH" stage and initial improvement of certain psycho-motory functions (reaction time, attention, awareness), cause an incapacity by altering risk perception [12,13]. The initial stimulating effects are soon substituted by tremors, hypertension, tachycardia and, in the case of amphetamines, increase in body temperature and manifestation of epileptic convulsions. In the "DOWN" phase, debilitating effects follow such as depression, irritability, fatigue and anxiety attacks. The down phase can occur a early as 45 minutes after ingestion and has a duration of 2-4 days. As for amphetamine derivatives (e.g. ecstasy) physical and behavioural effects manifest after just a few minutes of ingestion, and protract up to six hours. Such effects, due to a generalized stimulation of the central nervous system, include: euphoria, hyperexcitability, nervousness, tachycardia, insomnia, anorexia, bruxism and mydriasis. Paradoxically, such effects are accompanied by a sense of wellbeing and relaxation and some ameliorative psychological effects. Among the chronic effects are deficits in cognitive functions (memory loss, difficulty concentrating and learning) and psychotic flashbacks. For both hallucinogens and psycho-stimulants drugs, studies of man-machine interaction demonstrate: an increase in dynamic variations of the motor vehicle, both in a lateral and longitudinal (waving) direction; maintenance of high speed; notable reduction of safety distances; reduced reaction to sound and visual stimuli (mydriasis). The above-mentioned effects, indicators of a considerable risk of road crashes and accidents [14], are accentuated or favoured by the combined intake of ethylic alcohol or the increase in drug dose (lateral undulations, increase

The role of natural **opiates**, *Methadone* and *Buprenorphine* in the determination of road accidents is still debated. The verified effects on the incapacity to drive correlate to mood changes, reduced motor coordination, drowsiness, slower psychomotor coordination and pupillary constriction. Withdrawal symptoms and frequent association with other psychoactive substances take on considerable importance, particularly with ethyl alcohol. For some authors Methadone Maintenance Treatment is thought to impede capacity to drive, until psychic stabilisation (> 1 year) and secure absence of the co-use of other psychoactive substances. Buprenorphine in healthy subjects increases reaction time in a laboratory test but not in a

Studies that have evaluated all medications employed in heroine dependence therapy have shown that the parameters of competence (deviation from the lateral standard position, speed and capacity to steer round a bend, reaction to stimuli), do not present a difference in treated

**Gamma hydroxybutyrate** (GHB), a natural constituent of diverse systems and apparatus of the human organism, also a drug used in anaesthesiology therapy and in the treatment of

patients *vs* controls, except in the case of combined intake of ethylic alcohol [15].

distortion and depersonalisation, often leading to suicide attempts.

92 Toxicology Studies - Cells, Drugs and Environment

in speed and reaction times).

simulation driving test.

As far as **medicinal drugs** are concerned**,** there is an *ample difference* between the effects of psychotropic *medicines* belonging to the *same therapeutic class.*

Among *Antidepressants*, *Barbiturates*, *Benzodiazepines*, *Hypnotics* and *Neuroleptics,* are disabling medicines and medicines for which the conclusions are not definitive. Also among *Anxiolot‐ ics* and *Antihistamines* coexist disabling drugs and drugs free from effects.

In particular, psychopharmacological studies of man-machine interactions (real and simulated driving test, laboratory test) have identified: drugs that induce an incapacity to drive; drugs that determine a positive effect on the capacity to drive; drugs that do not determine any effect [17].

An analytical systematic research in the field of Alcohol, Drugs and Driving poses particular problems regarding: correct blood sampling, which requires skin disinfection with an alcohol free liquid and blood drawing with a vacutainer vial containing suitable preservatives and anticoagulants; urine sampling, carried out under visual control; use of a chain of custody that documents time, place and personnel engaged in collection and transfer of samples; written consensus to sample collection and analysis given by the subject suspected of DUI, when considered by statuary laws; analytical procedures to be adopted; conservation of specimens in case of possible contestation.

Analytical procedures for the determination of BAC must be in headspace gas-chromatogra‐ phy with a suitable specific detector, whereas the determination of ethanol by enzymatic methods in serum or urine is not suitable for a report of medico-legal value.

The range of substances that must be determined qualitatively and quantitatively is wide, and includes both scheduled and prescription drugs (e.g. benzodiazepines, Z drugs), depending on specific Country legislation. It is thus necessary to have more validated methods available, both in GC-MS and LC-MS, and adequate reference standards. In the evaluation phase, only concentrations identified in the blood may be related to the state of impairment, although there is no univocal approach: in some Countries, threshold values are given by law (blood cut-off) to determine riving impairment, in other Countries no values are set and every concentration is considered impairing (*zero tolerance*).

For the use of oral fluid as the biological fluid for road side DUI controls, the following problems arise: absence of standardized procedure for sample taking; frequent paucity of specimen compared to conventional matrices (e.g. blood) with consequent limitations of multiclass analyses and counter analyses; greater concentration of active compounds than their metabolites, detectable at low concentrations if not sometimes absent; variability of the relationship between salivary and blood concentrations, depending on the variability of the salivary pH, in turn dependent on the speed of saliva production; the possibility of oral contamination as a result of endonasal or inhalatory intake (smoking) of a substance, with a consequent increase of the salivary concentration, independent of the blood concentration.

In light of such criticality, analyses on saliva specimen introduce prospects of controversy connected to analytical, kinetic and evaluative problems.
