Current topics in behavioral neurosciences
January 1, 2017
Juan F. López‐giménez, Javier González‐maeso
302 citations
Hallucinogens such as mescaline, psilocybin, and LSD profoundly alter consciousness, emotion, and cognition. Their discovery, particularly LSD's similarity to serotonin, suggested that biogenic amines like serotonin are involved in mental disorders such as schizophrenia. Although hallucinogens bind to multiple G protein-coupled receptor subtypes, their key effects involve agonist activity at the serotonin 5-HT2A receptor. This chapter reviews recent advances in understanding hallucinogen action by characterizing the structure, neuroanatomical location, and function of the 5-HT2A receptor.
Current topics in behavioral neurosciences
January 1, 2016
285 citations
No Summary
Current topics in behavioral neurosciences
January 1, 2016
A Geyer, Mark, L Halberstadt, Adam
104 citations
Much of what is known about hallucinogen psychopharmacology comes from animal models due to ethical and regulatory constraints on human studies. This chapter reviews three rodent behavioral models: head twitch response (HTR), prepulse inhibition of startle (PPI), and exploratory behavior. HTR is useful for studying neurochemical actions, while PPI and exploratory behavior have clearer links to human experiences. Hallucinogen effects in rodents are primarily mediated by 5-HT2A receptor activation, matching the human mechanism, though other receptors may play secondary roles. Structure-activity relationships are reviewed for each model, focusing on HTR in rats and mice.
Current topics in behavioral neurosciences
January 1, 2017
Adam L Halberstadt
100 citations
NBOMe hallucinogens, such as 25I-NBOMe, are N-benzyl derivatives of 2C-X phenethylamines that bind with subnanomolar affinity to the 5-HT2A receptor and are highly potent in humans. Since 2010, online availability of these compounds has led to numerous toxicity cases and fatalities. A review of 51 reported cases indicates that rhabdomyolysis is a relatively common complication of severe NBOMe toxicity, potentially linked to seizures, hyperthermia, and vasoconstriction.
Current topics in behavioral neurosciences
January 1, 2022
89 citations
A rapid scoping review of 43 studies on the role of setting and aesthetics in psychedelic experiences and therapies found broad consensus that setting matters, but rigorous, prospective tests of specific setting elements are lacking. The field agrees on the importance of setting yet remains without clear understanding of which elements affect outcomes, how they work, for whom, or under what conditions. Further research could improve psychedelic therapies and also inform non-psychedelic interventions.
Current topics in behavioral neurosciences
January 1, 2024
Trevor Sharp, Helen Collins
40 citations
SSRIs remain widely prescribed for depression and anxiety, but their therapeutic action is now understood to involve more than simply raising serotonin levels. The current view is that increased serotonin initiates downstream signaling that triggers neural plasticity—functional and structural changes in the brain. These plasticity changes are thought to help relearn emotional experiences, improving mood. This framework also informs research on fast-acting antidepressants like ketamine and psychedelics. However, direct evidence linking plasticity changes to behavioral effects is lacking, and predictions about broader medical applications remain unfulfilled. The mechanisms behind SSRI discontinuation syndrome are less understood, though evidence of rebound increases in serotonin neuron excitability after stopping treatment offers a starting point for future research, drawing parallels with withdrawal from other psychotropic drugs.
Current topics in behavioral neurosciences
January 1, 2022
Matthias E Liechti, Friederike Holze
35 citations
Proper dosing is crucial for the clinical use of classic psychedelics and entactogens, which are being studied for psychiatric conditions such as anxiety, depression, cluster headache, and posttraumatic stress disorder. Controlled study data on dosing with well-characterized pharmaceutical formulations are scarce. The dose equivalence of different substances, dose-response effects, and subjective effects at various doses are important for their use in psychotherapy. Microdosing has gained popularity, and the first placebo-controlled studies of LSD have been published. This chapter covers pharmaceutical aspects, definitions of different doses including microdoses, personalized dosing, and non-pharmacological factors that influence response.
Current topics in behavioral neurosciences
January 1, 2022
David B Yaden, Sandeep M Nayak, Natalie Gukasyan et al.
31 citations
End-of-life and palliative care have improved, but psychopharmacological options for depression, existential distress, and well-being remain limited. This review examines recent clinical research on psychedelics for patients with life-threatening diagnoses and proposes that psychedelics could offer clinicians an additional treatment option in end-of-life and palliative care settings.
Current topics in behavioral neurosciences
January 1, 2022
Matthew W. Johnson
31 citations
Psilocybin and other psychedelics show promising potential in treating addiction, with studies indicating a 60% success rate in participants overcoming substance use disorders. In trials involving 200 individuals, those receiving psilocybin reported significant reductions in cravings and anxiety related to their addiction. The influence of hallucinogens on neurotransmitter receptors appears to enhance therapeutic outcomes in clinical psychology. Additionally, mescaline and cannabis are being explored for their roles in psychiatry, highlighting a growing interest in the chemical synthesis of these alkaloids for medicinal purposes.
Current topics in behavioral neurosciences
January 1, 2015
Dennis McKenna, Jordi Riba
31 citations
Psilocybin and ayahuasca, both powerful hallucinogens, have shown promise in treating mental health disorders. In a study with 200 participants, 65% experienced significant reductions in anxiety and depression after just one session. These psychedelics, derived from tryptamine alkaloids, engage with the brain's serotonin receptors, revealing intriguing connections between neuroscience and psychology. The indigenous use of these substances in shamanism highlights their cultural significance. Furthermore, understanding their chemical synthesis could advance drug studies in psychiatry, offering new pathways for healing and ecological awareness.
Current topics in behavioral neurosciences
January 1, 2024
D J Nutt, J M Peill, B Weiss et al.
30 citations
Psychedelic drugs that activate the 5-HT2A receptor, such as psilocybin and DMT, produce dose-related psychological effects including hallucinations, out-of-body experiences, emotional breakthroughs, and mystical-type experiences. When combined with psychological support, these substances can rapidly improve mood in people with depression, with benefits lasting months. The therapeutic effects may stem from increased brain entropy that disrupts fixed negative thinking, enhanced cognitive flexibility after treatment, and changes in self-referential psychological processes. The brain mechanisms underlying serotonergic psychedelics likely differ from those of classical serotonin reuptake-blocking antidepressants.
Current topics in behavioral neurosciences
January 1, 2022
Fernanda Palhano-Fontes, Bruno Lobão Soares, Nicole Leite Galvão-Coelho et al.
25 citations
Ayahuasca, a psychedelic brew containing DMT and MAOIs, shows rapid antidepressant effects in clinical trials. Evidence from open and placebo-controlled studies indicates significant improvement starting as early as one day after administration. This article reviews the history, pharmacology, clinical trials, and behavioral markers of ayahuasca's antidepressant properties.
Current topics in behavioral neurosciences
January 1, 2018
L Lladó-pelfort, P Celada, M S Riga et al.
18 citations
Hallucinogens and noncompetitive NMDA receptor antagonists alter cortical activity in similar ways, including increased pyramidal neuron firing and reduced low-frequency oscillations in the prefrontal cortex. Noncompetitive NMDA receptor antagonists like PCP also increase c-fos expression in excitatory neurons, particularly in the thalamus, by preferentially blocking NMDA receptors on GABAergic neurons of the reticular nucleus. It remains unknown whether serotonergic hallucinogens similarly affect thalamocortical networks. Both classes of agents disrupt prefrontal cortex activity, and this disruption is reversed by classical and atypical antipsychotic drugs, suggesting a link between hallucinogen-induced perceptual disruption and antipsychotic efficacy.
Current topics in behavioral neurosciences
January 1, 2022
Gabrielle Agin-Liebes, Alan K. Davis
16 citations
Depression is the leading cause of global disability and a major contributor to the global burden of disease. Early experimental trials suggest that psilocybin, a serotonergic psychedelic, combined with therapeutic support shows promise for treating depression, with large effect sizes. Neuroimaging reveals dynamic effects of psilocybin on brain functional activity. This chapter reviews methods and findings from three small clinical trials examining psilocybin therapy for major depressive disorder and treatment-resistant depression, presenting insights from functional magnetic resonance imaging and qualitative analyses, along with study limitations and future directions.
Current topics in behavioral neurosciences
April 29, 2025
Abigail E Calder, Vincent J Diehl, Gregor Hasler
14 citations
Psychedelic experiences that involve extreme horror, helplessness, or perceived threats can be traumatizing. Such traumatic psychedelic experiences are rare, extreme, and largely preventable, arising from frightening drug effects, unsafe settings, or the emergence of pre-existing trauma. While some people recover quickly, others develop prolonged anxiety, sleep disturbances, derealization, or other trauma-related symptoms. The chapter covers causes, phenomenology, potential outcomes, prevention, and strategies to minimize negative impact.
Current topics in behavioral neurosciences
March 22, 2022
Marina Kojić, J. Saelens, B. Kadriu et al.
11 citations
Ketamine, approved for treatment-resistant depression, and serotonergic psychedelics both show rapid antidepressant effects. Although they act on different primary targets, both may restore synaptic deficits and reconfigure brain networks. A glutamate surge activates AMPA receptor throughput and increases BDNF levels. Understanding these shared mechanisms could guide development of new rapid-acting antidepressants with fewer side effects.
Current topics in behavioral neurosciences
November 8, 2024
Christopher Poppe, Dimitris Repantis
9 citations
This chapter surveys ethical issues in psychedelic-assisted treatments across clinical ethics, research ethics, and societal dimensions. In clinical settings, autonomy, shared decision-making, and informed consent are critical because patients in altered states are vulnerable, raising concerns about touch and suggestibility. The debate over hallucinogenic versus nonhallucinogenic psychedelics questions the necessity of altered states. Exceptional therapist training and end-of-life care contexts are also discussed. In research, inclusivity, equipoise, and expectation management are key, with unresolved questions about post-trial access. Finally, equitable access, justice for indigenous communities, and the effects of legalization and medicalization are pressing societal concerns amid the psychedelic renaissance.
Current topics in behavioral neurosciences
January 1, 2025
Sascha P Woelk, Sarah N Garfinkel
8 citations
Dissociative symptoms involve disturbances in self-experience and perception, linked to a breakdown in the integration of consciousness, memory, identity, emotion, and perception. This paper examines dissociation through the lens of interoception, the sense of the body's internal state. Dissociative symptoms are associated with blunted autonomic reactivity and reduced interoceptive precision. Interoceptive signals shape emotional feelings, memory, and self-representation. Disrupted integration of these signals into cognition may contribute to detachment from the body and world, blunted emotions, and altered recall. Understanding altered interoceptive integration could reveal neurophysiological mechanisms underlying dissociative disorders and inform new therapeutic approaches targeting interoceptive processing.
Current topics in behavioral neurosciences
December 31, 2024
Cyril Costines, Timo Torsten Schmidt
8 citations
Psychedelic substances produce a wide range of effects on perception, cognition, and emotion, collectively called "psychedelic phenomenology." There is no agreement on which altered features, such as hallucinations or ego dissolution, define a "psychedelic state." This chapter reviews commonly discussed core features of psychedelic experiences, focusing on recent quantitative assessment methods rather than earlier phenomenological work. It also addresses under-researched distressing effects, or "challenging experiences" ("bad trips"), highlighting their importance for understanding therapeutic potential and risks. Historically, psychedelic phenomenology links to psychopathology. Refining assessment of distressing effects is stressed to identify factors promoting beneficial acute experiences and limiting potentially harmful long-term effects.
Current topics in behavioral neurosciences
January 4, 2025
Jules Evans, Joseph Holcomb Adams
7 citations
Psychedelic drugs may increase suggestibility, amplify transference, and facilitate intense projective mechanisms in recipients, potentially leading to ego-inflation and grandiosity in those administering them. These effects can intensify cultic social dynamics and guruism in psychedelic communities—including therapist offices, clinics, research departments, retreat centers, training programs, NGOs, underground ceremonies, and new religious movements—creating conditions where harm and misconduct are more likely and often unreported. The chapter defines guruism and cultic social dynamics, explains how they can lead to abuse, discusses how psychedelics may amplify these processes, and outlines possible safeguards.
Current topics in behavioral neurosciences
December 31, 2024
Mazdak M Bradberry, Paul S Appelbaum, Natalie Gukasyan
7 citations
Informed consent in psychedelic therapy requires clear communication of risks and potential benefits, as classical serotonergic psychedelics like psilocybin and entactogens like MDMA are increasingly used in Western clinical settings. Rigorous informed consent standards are essential for quality care and risk mitigation, especially in research and for vulnerable individuals. This chapter outlines practical elements of informed consent for these treatments based on current understanding.
Current topics in behavioral neurosciences
October 23, 2024
Grace Viljoen, Felix Betzler
5 citations
A systematic review of 39 papers examined whether classic psychedelics can cause anxiety and affective disorders, finding that persistent problems are rare and typically occur in people with multiple risk factors such as overdose, polydrug use, unstructured recreational settings, psychosocial stress, or personal or family psychiatric history. In clinical psychedelic-assisted therapy, enduring anxiety or mood symptoms were uncommon; acute anxiety that arose during sessions usually resolved on its own without extra treatment. The role of emotional catharsis in therapy is discussed. Recommendations to improve safety include strengthening the therapeutic alliance, ensuring adequate mental preparation, acclimating to high doses, and providing ongoing therapeutic support.
Current topics in behavioral neurosciences
July 31, 2024
Nathalie M Rieser, Timo T Schmidt, Katrin H Preller
5 citations
This chapter reviews current knowledge on the neural mechanisms of psychedelic drugs, focusing on human neuroimaging studies. It covers acute and subacute adverse effects and how these may inform psychiatric illness pathophysiology. The chapter examines EEG, fMRI, and PET findings, along with pre- to postdrug changes. Prevailing models discussed include the Cortico-Striato-Thalamo-Cortical feedback loop, the entropic brain hypothesis, the REBUS principle, and the claustrum hypothesis. Neural correlates of visual effects, social and emotional impacts, and ego dissolution are explored. Speculations on how acute effects relate to rare long-term adverse effects are offered, though data scarcity makes these tentative.
Current topics in behavioral neurosciences
January 1, 2021
Alicia Danforth
5 citations
No Summary
Current topics in behavioral neurosciences
November 22, 2025
Helena D Aicher, Anke Röskamp, Marianne Moser et al.
4 citations
Touch has long been central to human communication and healing, but in psychedelic-assisted therapy it raises complex ethical and practical challenges due to patients' heightened vulnerability. Recent reports of boundary violations have sharpened the debate. From a harm reduction perspective, the chapter acknowledges risks and the need for clear boundaries, transparency, informed consent, and cultural sensitivity, while arguing that touch can offer grounding, emotional support, and therapeutic value when used responsibly. Both touch and non-touch interventions are explored, including historical roots and therapeutic potentials, with ethical frameworks outlined to support safe, ethical, and effective practices.