Psychedelic Research

Psychedelics are a class of drugs that induce profound altered states of consciousness, including acute alterations in perception and cognition, and amplified emotional states. Substances include classic psychedelics like lysergic acid diethylamide (LSD), psilocybin and dimethyltryptamine (DMT), and empathogens like methylenedioxymethamphetamine (MDMA).

Recently, there has been renewed interest in the therapeutic potential of these substances for mental disorders like depression, anxiety, and post-traumatic stress disorder. Anecdotal reports suggest that they may provide therapeutic relief for individuals whose current treatment options are ineffective. A growing number of clinical studies have also shown very promising results. Recently, we demonstrated the rapid improvement of depression symptoms in treatment-resistant depression patients, following administration of varying doses of GH-001 (5-MeO-DMT) (Figure 1). However the underlying mechanisms of action of these substances and their efficacy have yet to be fully elucidated.

Utilizing multimodal study designs, our research focuses on assessing the neurobiological and cognitive mechanisms (see Figure 2) of psychedelic drugs in regular and low doses (i.e., microdosing) (see Figure 3), with a particular focus on those that may lead to enhancements in psychological well-being. Here we are particularly interested in changes in brain function, cognitive/psychological flexibility, and (pro)-social behavior. We examine these processes via experimental, naturalistic, and survey studies.

Additionally, animal studies with psychedelics have shown that these drugs can stimulate the creation of new connections between neurons, a process which is referred to as neuroplasticity (de Vos et al., 2021). Since neuroplasticity underlies important cognitive functions such as psychological flexibility and emotion regulation, this effect of psychedelics may explain the persisting positive effects on mood and cognition observed in our human studies (Magaraggia et al., 2020). However, measuring neuroplasticity in humans is challenging due to the limited methods available for assessing the cellular and molecular aspects of brain functioning in non-invasive manners. Therefore, our team is exploring new methods to study the molecular effects of psychedelics at the level of neuroplasticity in the brain by measuring the blood content and brain activity after exposing participants and patients to psychedelic treatments. For example, we are looking at qualitative and quantitative changes in the levels of protein and genetic material that are known to play a role in neuroplasticity such as brain-derived neurotrophic factor (Hutten et al., 2020), and microRNAs contained inside brain-derived particles (i.e., extracellular vesicles).

  • Creativity is an essential cognitive ability linked to all areas of our everyday functioning. Thus, finding a way to enhance it is of broad interest. A large number of anecdotal reports suggest that the consumption of psychedelic drugs can enhance creative thinking; however, scientific evidence is lacking.

  • Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use.

  • ADHD in adulthood is often overlooked, which negatively affects the individual’s well-being. First-line pharmacological interventions are effective in many ADHD patients, relieving symptoms rapidly. However, there seems to be a proportion of individuals who discontinue, or fail to respond to these treatments. For these individuals, alternative treatment options should be explored.

  • There is a popular interest in microdosing with psychedelics such as LSD. This practice of using one-tenth of a full psychedelic dose according to a specific dosing schedule, anecdotally enhances mood and performance. Nonetheless, controlled research on the efficacy of microdosing is scarce. The main objective of the present dose-finding study was to determine the minimal dose of LSD needed to affect mood and cognition.

  • The knowledge that brain functional connectomes are both unique and reliable has enabled behaviourally relevant inferences at a subject level. However, it is unknown whether such “fingerprints” persist under altered states of consciousness.

  • The phenethylamine 4-fluoroamphetamine (4-FA) is a so-called novel psychoactive substance with a chemical structure resembling that of amphetamine and MDMA.

  • Lysergic acid diethylamide (LSD) is an ergot alkaloid derivative with psychedelic properties that has been implicated in the management of persistent pain. Clinical studies in the 1960s and 1970s have demonstrated profound analgesic effects of full doses of LSD in terminally ill patients, but this line of research evaporated after LSD was scheduled worldwide.

  • The purpose of this study was to compile usage patterns and adverse event rates for individual NPs belonging to each of three main psychedelic structural families.

  • 2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens.

  • Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities.

  • Ayahuasca is a South American psychotropic plant tea traditionally used in Amazonian shamanism. The tea contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT), plus β-carboline alkaloids with monoamine oxidase-inhibiting properties.

  • There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression.

  • The first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-MeO-DMT on affect and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience.

  • Microdosing with psychedelics has gained considerable media attention where it is portrayed as a performance enhancer, especially popular on the work floor. While reports are in general positive, scientific evidence about potential negative effects is lacking aside from the prevalence and motives for use.

  • In the past few years, the issue of ‘microdosing’ psychedelics has been openly discussed in the public arena where claims have been made about their positive effect on mood state and cognitive processes such as concentration. However, there are very few scientific studies that have specifically addressed this issue, and there is no agreed scientific consensus on what microdosing is.

  • Despite preclinical evidence for psychedelic-induced neuroplasticity, confirmation in humans is grossly lacking. Given the increased interest in using low doses of psychedelics for psychiatric indications and the importance of neuroplasticity in the therapeutic response, this placebo-controlled within-subject study investigated the effect of single low doses of LSD

  • Evidence is accumulating that psychedelics may possess antidepressant activity, and this can potentially be explained through a multi-level (psychobiological, circuitry, (sub)cellular and molecular) analysis of the cognitive systems RDoC domain.

  • We conducted a placebo-controlled, parallel group design comprising of 60 healthy participants who received either placebo (n=30) or 0.17 mg/kg psilocybin (n=30). Blood samples were taken to assess acute changes in immune status, and 7 days after drug administration.

  • Decades ago, the classical psychedelics psilocybin and LSD entered the therapeutic setting and already then showed their therapeutic potential in the treatment of psychiatric disorders. For thousands of years another psychedelic, ayahuasca, is being used by tribes in western Amazonia for healing and divination, and in recent years its use has expanded worldwide.

  • Using 7T fMRI, we assessed resting-state static and dynamic FCs for 21 Santo Daime members after collective ayahuasca intake in an acute, within-subject study.

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