Driving under the Influence of Psychotropic Substances: A Technical Interpretation
Abstract
:1. Introduction
2. Methods and Applicable Legislation
3. Specific Aspects of Legislation
4. Specific Interpretations
4.1. The Cannabinoids
- The law defines Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) as illicit substances.
- While Δ9-THC and THC-OH are pharmacologically active (i.e., they can influence cognitive abilities for road driving), THC-COOH is not, and as such, does not influence function.
- THC-COOH has a long half-life (t1/2) and a large detection window, far beyond the manifestation of acute effects [8].
- In fact, in occasional cannabis smokers, THC-COOH was found up to 7 days after the last use [9].
- Therefore, THC-COOH is the compound within this group that is most often detected.
- Nevertheless, although it can be detected, its presence should not be used for the assessment of the state of influence, because it has no affinity for the cannabinoid receptor and therefore has no recognized psychoactive effect [10].
- In other words, it may be said that an in-control has concentrations of 18 ng/mL THC-COOH or 18 ng/mL Δ9-THC in blood.
- However, it should be clarified that the THC-COOH positivity, undoubtedly means that a driver consumed Δ9-THC.
- Tolerance to Δ9-THC can be developed, meaning that for equal concentrations of Δ9-THC, regular consumers may be less influenced than occasional consumers [11].
- Some studies have proposed interpretations based on blood concentrations that are listed below because the state of influence is largely dependent on biological concentrations [14].
- In occasional consumers and in the case of recent consumption, Δ9-THC concentrations of 2–5 ng/mL are usually associated with states of influence [15].
- Concentrations greater than 5 ng/mL are equivalent to an accident risk approximately equal to the alcohol rate of 1.5 g/L [16].
- Concentrations of 7–10 ng/mL Δ9-THC in serum (3.5–5 ng/mL in whole blood) cause a state of influence similar to BAC of 0.5 g/L [17].
- The state of influence increases 2.4, 2.5 and 3.2 for concentrations of Δ9-THC in the blood of 3.0–4.8, 4.9–10.1 and >10.2 ng/mL, respectively [11].
- Values below 2 ng/mL indicate no influence [14].
- For concentrations greater than 2 ng/mL, performance impairment was seen for some, but not all, driving-related tasks [14].
- For concentrations of 2–5 ng/mL Δ9-THC, 71% of influenced individuals; for 5–10 ng/mL, 75–90% of individuals are influenced, and for concentrations greater than 30 ng/mL, 100% are influenced [14].
- In some countries, such as the United Kingdom, limits of 2 μg/L for Δ9-THC have been set so as not to accidentally penalize drivers exposed to passive consumption and due to the inherent analytical difficulties associated with enforcing a 0.0000 μg/L limit.
4.2. Cocaine and Metabolites
- Cocaine use is associated with an average of 2 to 10 times higher risk of serious injury or fatality in road accidents, according to the findings of the Project Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) [19].
- This risk is similar to driving with a BAC between 0.5 g/L and 0.8 g/L [20].
- Cocaine is mainly metabolized by 2 pathways: major benzoylecgonine and ecgonin methyl ester metabolites and several other minor metabolites.
- For the purposes of Law No. 18/2007 of 17 May, only cocaine and its main metabolite, benzoylecgonine, which comes from spontaneous hydrolysis or the action of human carboxylesterase 1, were analyzed [21].
- Since benzoylecgonine is inactive this is a method of detoxification and lacks psychoactive activity [22]. Thus, if this compound is found (and with negative cocaine) it does not mean that the individual is under the influence of this psychoactive substance.
- However, it should be clarified that benzoylecgonine positivity undoubtedly means that the driver is a consumer of illicit substances, specifically cocaine.
- In other words, while cocaine may be absent from a blood sample after 4 to 6 h, benzoylecgonine may be present for up to 6 days after cocaine administration, especially in chronic users.
- In some countries, such as the United Kingdom, limits of 50 μg/L benzoylecgonine and 10 μg/L cocaine have been defined so as not to penalize accidentally exposed drivers, because of passive consumption.
4.3. Opiates
- Consideration should be given to the fact that many pharmaceutical formulations (e.g., used as analgesics and antitussives) have codeine and morphine, and therefore may produce a positive opiate but not due to illicit consumption. Despite being an omitted legislation, in these cases, the licit consumption can be easily attested by a medical prescription.
- For example, codeine undergoes O-demethylation, catalyzed by CYP2D6 and 2D7, resulting in morphine. Thus, morphine is present when patients are administering codeine [31]. It is even plausible that morphine has been administered per se, especially in hospital for the for severe pain in cases of extensive traumatic injuries.
- In this case, it is necessary, when possible, that the collection of biological samples be made before starting therapeutic measures.
- The presence of 6-acetylmorphine (6-AM) is evidence of recent heroin use, since it results from hydrolysis of heroin catalyzed by human carboxyesterase-1 and 2 in the liver and brain and plasma butyrylcholinesterase [31].
- The very reduced t1/2 of heroin means it cannot be used for analysis to document its consumption.
- For morphine, its t1/2 of approximately 1 to 3 h extends its blood window of detection to 10 to 15 h after ingestion [41].
- In some countries, such as the United Kingdom, even applying a zero-tolerance regime, the limit of 5 μg/L for 6-acetylmorphine is used so as not to penalize accidentally exposed drivers, because of passive consumption or high values of 80 μg/L for morphine because of its large therapeutic application [42].
4.4. Amphetamines and Derivatives
- The interpretation for this group is more obvious, since the compounds considered in Law No. 18/2007 of 17 May are all pharmacologically active.
- Nevertheless, it is important to highlight the fact that methamphetamine is metabolized to amphetamine and 3,4-methylenedioxymetamphetamine (i.e., MDMA or ecstasy) and 3,4-methylenedioxyethylamphetamine (MDEA or MDE) are metabolized into 3,4-methylenedioxyamphetamine (MDA) [45], which is more potent than the former [46].
- Therefore, the assessment of these compounds may give rise to erroneous presumptions regarding the type of substance that was consumed.
- 1,3-benzodioxolil-N-methylbutanamine (i.e., 3,4-methylenedioxy-N-methyl-α-ethylphenylethylamine; MBDB) has little or no expression (including compared to other substances not included in the law) and is metabolized to its active metabolite 1-(3,4-methylenedioxyphenyl)-2-butanamine (BDB) [47].
- In some countries, such as the United Kingdom, even applying a zero-tolerance regime, a limit of 250 μg/L for amphetamine has been established by recognizing its therapeutic applications (e.g., attention deficit hyperactivity disorder and narcolepsy). Despite the potential therapeutic application, it should be highlighted that it does not mean they are safe in terms of driving. For methamphetamine and 3,4-methylenedioxyamfetamine, minimum limits of 10 μg/L were set so as not to be penalized due to accidental exposure.
5. About the Inclusion of Other Compounds
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Dinis-Oliveira, R.J.; Magalhães, T. Driving under the Influence of Psychotropic Substances: A Technical Interpretation. Psychoactives 2022, 1, 7-15. https://doi.org/10.3390/psychoactives1010002
Dinis-Oliveira RJ, Magalhães T. Driving under the Influence of Psychotropic Substances: A Technical Interpretation. Psychoactives. 2022; 1(1):7-15. https://doi.org/10.3390/psychoactives1010002
Chicago/Turabian StyleDinis-Oliveira, Ricardo Jorge, and Teresa Magalhães. 2022. "Driving under the Influence of Psychotropic Substances: A Technical Interpretation" Psychoactives 1, no. 1: 7-15. https://doi.org/10.3390/psychoactives1010002