Review of Selected 2-Phenylethylamine Derivatives and Opioids, Systematic Review of Their Effects on Psychomotor Abilities and Driving Performance: Psychopharmacology in the Context of Road Safety
Kacper Żełabowski, Kamil Biedka, Wojciech Pichowicz, Maria Sterkowicz, Izabela Radzka, Ignacy Ilski, Michał Wesołowski, Kacper Wojtysiak, Wiktor Petrov, Dawid Ślebioda, Maciej Rząca, Agnieszka Chłopaś-konowałek
Pharmaceuticals October 28, 2025 DOI: 10.3390/ph18101555 via DOAJ
Summary
The effects of psychoactive substances on driving performance depend on dose, tolerance, and medical condition. Therapeutic amphetamine and methylphenidate can improve psychomotor function and safety in patients with ADHD, while recreational or high-dose methamphetamine and MDMA impair coordination and increase impulsivity. Opioid effects vary: small therapeutic fentanyl doses in chronically treated patients do not notably impair driving, but methadone and tramadol commonly cause somnolence, slowed reactions, and higher accident risk. The review confirms that substance impact is multifactorial and supports individualized pharmacotherapy and further research for evidence-based guidelines.
Study at a glance
| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Population | Adult participants in studies of PEA derivatives or opioids and driving-related psychomotor function |
| Keywords | Psychopharmacotherapy Drug abuse Psychoactive substances Psychomotor performance Driving safety |
| Key finding | Therapeutic amphetamine and methylphenidate can enhance driving safety in ADHD patients, whereas recreational methamphetamine and MDMA impair performance, and opioid effects range from no impairment with low-dose fentanyl to increased accident risk with methadone and tramadol. |
Abstract
Background: Driving is a coordinated psychomotor activity that involves reaction time, attention, and decision-making. Psychoactive substances such as 2-phenylethylamine (PEA) derivatives and opioids may affect these functions and contribute to traffic safety. This systematic review revealed the effects of the selected PEA derivatives and opioids on psychomotor performance among drivers and potential road safety outcomes. Methods: The review followed PRISMA 2020 standards. Using the PICO method, we conducted a systematic search in Embase, PubMed, and Web of Science (2000–2025). Included studies involved adult participants and quantified the effect of PEA derivatives or opioids on driving-related psychomotor function. Thirty-one articles, such as randomized controlled trials, crossover studies, observational studies, and simulator-based studies, were examined. Risk of bias was evaluated using the RoB2 tool. Results: Evidence indicates therapeutic amphetamine and methylphenidate doses can enhance psychomotor function and safety in patients with ADHD. Recreational or high-dose use of methamphetamine and MDMA is associated with impaired coordination, variable speed, and increased impulsivity. Opioid effects are tolerance- and dose-dependent. Small therapeutic doses of fentanyl in chronically treated patients do not notably impair driving. On the other hand, methadone and tramadol commonly cause somnolence, retardation of reaction, and increased accident risk. Conclusions: The impact of opioids and PEA derivatives on psychomotor function is multifactorial, depending on dose, time, route of administration, and patient status. These substances can either improve or impair driving safety. The findings confirm the need for individual-specific pharmacotherapy treatment. They also highlight the importance of further studies to formulate evidence-based clinical and legislative guidelines.