Psychopharmacology

Cannabis is widely used globally, with 2.7–4.9% annual prevalence and high lifetime use. Its main psychoactive compound, THC, produces relaxation and euphoria but can impair memory, attention, executive function, and driving-related skills, sometimes causing anxiety or paranoia. In contrast, CBD is non-psychoactive and may have anxiolytic and antipsychotic effects. We conduct laboratory and field studies to examine THC’s neurocognitive, neurophysiological, and pharmacokinetic effects in occasional and chronic users, including impacts on memory, inhibitory control, and criminal-event recall. Our research also explores cannabis induced neuroadaptations, synthetic cannabinoids, and individual variability, informing pharmacodynamic models and legal and clinical evaluations of cannabis-related impairment.

Aging is associated with a gradual cognitive decline, affecting memory, attention, and executive function. In some individuals, deterioration accelerates and can lead to dementia, including Alzheimer’s disease, for which effective treatments remain limited. Our department investigates novel therapeutic targets to improve cognition in aging and dementia, building on foundational work by Nobel laureate Eric Kandel. Rather than focusing solely on receptor activation, we target intracellular signaling pathways, particularly cyclic nucleotide cascades, to enhance neuroplasticity. Using pharmacological interventions such as the PDE4 inhibitor roflumilast, we have demonstrated memory-enhancing effects in both animal models and human studies. 

Sleep is equally critical for memory. Sleep deprivation impairs hippocampus-dependent memory and disrupts molecular signaling pathways required for consolidation. During sleep, memories undergo systems and synaptic consolidation, processes associated with slow-wave and REM sleep. We investigate whether sleep loss erases memory traces or merely weakens their retrieval. Our optogenetic and pharmacological studies suggest that information can persist in the brain and be artificially reactivated, an approach now translated to human research within the RDoC framework.

Finally, we examine so-called “smart drugs.” Although many supplements claim cognitive benefits, our research shows that while caffeine can enhance performance, multi-ingredient smart pills often provide no benefit beyond placebo. We are currently investigating placebo effects on cognition to better understand their magnitude and underlying mechanisms. 

In addition, we specifically focus on the diagnostics and interventions for neuropsychiatric symptoms that may accompany cognitive ageing.

Drowsiness-inducing medications can impair driving. Our group developed a highly sensitive on-the-road driving test using real traffic conditions to measure impairment via standard deviation of lateral position (SDLP), an indicator of weaving and crash risk. Applied in about 100 studies over 4 decades of research, it evaluates medicinal drugs and substances like cannabis and MDMA. Drug effects are compared to alcohol benchmarks, and SDLP strongly correlates with real-world crash risk, supporting its clinical relevance.

Psychedelics are drugs that produce profound altered states of consciousness, affecting perception, cognition, and emotion. Classic psychedelics such as LSD, psilocybin, and DMT, along with empathogens like MDMA, are gaining renewed interest for treating depression, anxiety, and PTSD. Using multimodal designs in clinical trials, we investigate neurobiological and cognitive effects of psychedelics, potential treatment applications and behavioural interventions to support or sustain therapeutic effects. Evidence suggests psychedelics promote neuroplasticity, potentially explaining lasting mood benefits. Our work explores molecular markers, including BDNF and microRNAs, to better understand therapeutic effects in humans. We also investigate microdosing paradigms, which involve repeated administration of very low doses that do not produce a full psychedelic experience, to assess subtle cognitive and affective effects. In addition, we study non-pharmacological approaches such as structured breathwork, which can induce altered states of consciousness through physiological regulation of breathing and may offer therapeutic potential in anxiety by modulating stress and emotional processing systems.

Within this research programme, we investigate how biological, cognitive, and environmental factors interact to shape stress responses and vulnerability to a broad range of stress-related mental and affective disorders, including depression, anxiety, sleep disturbances, and eating disorders. One line of research examines how chronic stress exposure increases the risk for mental and affective disorders as a function of genetic and cognitive vulnerability factors, such as neuroticism and the 5-HTTLPR genotype. In addition, we explore whether serotonin-enhancing nutritional interventions may modulate these relationships. A second focus addresses stress-induced habitual and addictive behaviours, with particular emphasis on the role of dopamine, while critically examining inconsistencies in laboratory findings. A third line of research investigates the impact of stress on memory processes, demonstrating that stress-induced activation of the HPA axis and subsequent cortisol elevations impair intentional forgetting through alterations in prefrontal and parietal brain mechanisms. Finally, we examine whether mindfulness training enhances cognitive control and thereby strengthens emotion regulation and psychological resilience. The fourth line focuses on traumatic stress and its association with dementia risk and neuropsychiatric symptoms.

Novel psychoactive substances (NPS) are unregulated compounds designed to imitate the effects of illicit drugs and carry significant risks of abuse and dependence. Often marketed as “legal highs” or “designer drugs,” they are widely available on the consumer market. Emergency intoxications—frequently involving cathinones, opioids, and synthetic cannabinoids, often combined with other substances or alcohol—are increasing, with symptoms including agitation, coma, and psychosis. Because current risk evaluations mainly rely on severe hospitalisation cases, we conduct controlled, dose-escalation clinical studies to better assess safety profiles and explore potential therapeutic applications under responsible use conditions.