N,N-Dimethyltryptamine: An Endogenous Hallucinogen
International review of neurobiology January 1, 1981 Steven A. Barker, John A. Monti, Samuel T. Christian 113 citations
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International review of neurobiology
ISSN 2162-5514
16 papers in the library · 172 citations · publishing 1981-2025
Papers
Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics.
International review of neurobiology January 1, 2016 L F Tófoli, D B De Araujo 25 citations
After a ban on psychedelic research in the late 1960s, covert studies continued through the 1990s, but the past decade has seen renewed scientific interest in substances such as LSD, ayahuasca, and psilocybin. This chapter reviews EEG and brain imaging studies that evaluate how psychedelics affect the brain. It also examines evidence for using psychedelics as adjunct therapy for psychiatric and addictive disorders, noting that psychedelics appear to have efficacy in treating depression and alcohol-use disorders.
Psychedelics and substance use disorder treatment.
International review of neurobiology January 1, 2025 Caitlin M. DuPont, Matthew W. Johnson 6 citations
Classic psychedelics, including LSD, psilocybin, and ayahuasca, show benefits for reducing drinking and achieving abstinence in alcohol use disorder, with small clinical trials also showing promising initial results for tobacco and opioid use disorders. No trials have yet been conducted for stimulant or cannabis use disorders. Most evidence comes from naturalistic observational studies or correlational survey data, which, combined with clinical trials, suggest potential broad transdiagnostic efficacy across multiple addictive drugs. These effects likely stem from biological improvements in brain areas involved in reward and emotional processing, reducing relapse risk, and psychological insights that reinforce personal motivations for sobriety. More work is needed to characterize benefits and limitations.
Ayahuasca for the treatment of alcohol use disorder.
International review of neurobiology January 1, 2024 Eduardo A V Marinho, Yasmim A Serra, Alexandre J Oliveira-Lima et al. 6 citations
Psychedelics such as LSD and psilocybin have shown promise for treating alcohol use disorder by reducing drinking and promoting abstinence. Ayahuasca, an Amazonian brew containing β-carbolines and DMT, has also emerged as a potential treatment. Clinical studies, mostly retrospective, report significant decreases in alcohol use among ayahuasca users. Pre-clinical evidence indicates ayahuasca blocks abuse-related effects of alcohol. The chapter reviews clinical and pre-clinical evidence suggesting ayahuasca may be a promising new pharmacotherapy for alcohol use disorder and discusses potential mechanisms.
Serotonin, immune function, and psychedelics as potent anti-inflammatories.
International review of neurobiology January 1, 2025 Charles D. Nichols, Timothy P. Foster 4 citations
Psychedelics, known for their behavioral effects, also influence the immune system through serotonin 5-HT2A receptors found throughout the body. Serotonin acting at these receptors generally promotes inflammation by increasing cytokine production, eosinophil recruitment, T-cell activation, and mast cell degranulation. However, some psychedelics show powerful anti-inflammatory and immunomodulatory effects via 5-HT2A receptor activation in preclinical models of human inflammatory diseases. Human studies are limited but suggest psychedelics may offer a new strategy for treating inflammatory conditions. This review covers serotonergic modulation of immune function, the role of 5-HT2A receptors, and key findings on psychedelics' anti-inflammatory efficacy.
Psychedelics for the treatment of end-of-life distress in patients with a life-threatening disease.
International review of neurobiology January 1, 2025 Stephan Tap, Tijmen Bostoen, Joost Breeksema et al. 4 citations
Patients with life-threatening disease often experience end-of-life distress—physical, psychological, emotional, and spiritual suffering linked to chronic illness and the prospect of death. Palliative care aims to improve quality of life, but current psychological and pharmacological interventions show inconclusive evidence with only short- to moderate effects and often require months to work. Over the past decade, psychedelic-assisted therapy has been investigated for addressing end-of-life distress, producing highly significant and sometimes sustained decreases in depression and death anxiety, along with improvements in meaning, spiritual well-being, optimism, life satisfaction, and attitudes toward disease. This chapter describes end-of-life distress, its prevalence, limitations of palliative interventions, the evidence for psychedelic-assisted therapy, why it may work for these patients, and future directions.
Cognitive and affective models of psychedelics in rodents.
International review of neurobiology January 1, 2025 Dasha Anderson, Emma S J Robinson 3 citations
Public and academic interest in psychedelics has grown due to clinical evidence of their potential benefits for treating major depressive disorder. Mechanistic studies in rodents remain relatively few but are crucial for understanding the neurobiological underpinnings of therapeutic effects. Findings from rodent studies will benefit patients only if they achieve translational validity. This chapter critically appraises rodent assays traditionally used to study cognition and affect, summarizing existing findings with psychedelics, and highlights novel, translationally valid assays. The authors argue that adopting translational assays is critical for interpreting animal studies of psychedelic effects, and that such studies can help unravel therapeutic mechanisms only if they involve relevant doses.
History of psychedelic drug science and molecular pharmacology.
International review of neurobiology January 1, 2025 David E Nichols, Charles D Nichols 3 citations
Classic psychedelics have been used for millennia for healing and religious purposes. Modern psychedelic science began in 1898 when Dr. Arthur Heffter identified mescaline as the active alkaloid in peyote. Western society's relationship with psychedelics has been contentious: initially valued as medicines and scientific tools, they were later criminalized during the 1960s counterculture, halting research for nearly 20 years. As the political climate shifted, clinical trials resumed, with high-profile studies demonstrating efficacy for psychiatric disorders. This review covers 125 years of psychedelic science, highlighting key events and findings that advanced understanding of their pharmacology, chemistry, and therapeutic potential.
Molecular brain imaging of psychedelic action.
International review of neurobiology January 1, 2025 Paul Cumming, Klemens Egger, Gitte M Knudsen 2 citations
Molecular brain imaging techniques such as PET and SPECT have been used since the 1980s to study psychostimulants, and more recently to investigate psychedelics. Most published research involves SPECT studies of cerebral blood flow and PET studies of metabolism and neuroreceptors, particularly the 5-HT2A receptor, which is primarily responsible for the effects of classical psychedelics. Some evidence documents interactions at dopamine D2/3 receptors in the striatum, but many other potential molecular targets remain unexplored. The growing therapeutic use of psychedelics for neurological and psychiatric disorders highlights the need for broader, systematic investigation of their effects on brain function.
The protective effect of DMT against neurodegeneration.
International review of neurobiology January 1, 2025 Ede Frecska, Attila Kovács, Attila Szabo 2 citations
DMT, an endogenous agonist of the sigma-1 receptor (Sig-1R) in addition to its serotonin receptor actions, shows therapeutic potential for neuroprotection against ischemia-reperfusion injury (IRI) and neurodegenerative disorders. Sigma-1 receptors are highly expressed in the brain and spinal cord and are implicated in central nervous system disorders. Previous theoretical and experimental work suggests targeting sigma and serotonin receptors via DMT may treat conditions like stroke, global brain ischemia, Alzheimer's disease, and amyotrophic lateral sclerosis. The paper reviews Sig-1R's role in cellular bioenergetics related to IRI and summarizes preclinical DMT studies that mitigated IRI and related neuropathologies. DMT's effect may involve universal cellular protective mechanisms, positioning it as a model molecule for developing treatments for neurodegenerative disorders.
Effects of psychedelics on human oscillatory brain activity.
International review of neurobiology January 1, 2025 Kate Godfrey, Lisa X Luan, Christopher Timmermann 1 citation
Classic psychedelics like LSD, psilocybin, ayahuasca, and DMT consistently reduce alpha power (8-13 Hz) in occipital regions, as measured by resting-state EEG and MEG. Below 30 Hz, desynchronization is typical, though DMT can preserve or increase delta/theta activity. Measures of signal diversity, such as Lempel-Ziv complexity, reliably increase during psychedelic states, indicating more variable neural firing. Real-time subjective intensity and plasma levels robustly covary with spectral and complexity changes, suggesting potential for real-time EEG biomarkers. Limited research on functional connectivity and cortical travelling waves hints at decreased top-down control and increased bottom-up signaling, a possible transient reversal of hierarchical organization, but replications are needed. EEG has yet to be evaluated in clinical studies.
Clinical pharmacology.
International review of neurobiology January 1, 2025 Severin B Vogt, Matthias E Liechti 1 citation
Serotonergic psychedelics such as psilocybin, LSD, mescaline, DMT, and 5-MeO-DMT produce comparable acute subjective and somatic effects primarily through interactions with 5-HT2A receptors, but their exact therapeutic mechanisms remain unclear. These classic psychedelics differ substantially in pharmacokinetics and metabolism, leading to different durations of action that may influence their suitability for specific therapeutic uses. MDMA has a distinct psychopharmacological profile with stimulant-like and empathogenic effects. Acute effects of psychedelics mirror their plasma-concentration-time curves, whereas MDMA's acute effects are shorter-lasting than its presence in the body, and MDMA exhibits marked acute pharmacological tolerance.
Post-traumatic stress disorder in psychedelic research.
International review of neurobiology January 1, 2025 Tijmen Bostoen, Stephan Tap, Joost Breeksema et al. 1 citation
MDMA-assisted therapy shows substantial and sustained reductions in PTSD symptoms, especially for patients resistant to conventional treatments. Over the past two decades, it has emerged as one of the most promising psychedelic treatments, with the FDA designating it a 'breakthrough therapy' in 2017. However, due to methodological concerns such as unblinding and potential expectancy effects, the FDA decided in 2024 not to approve it for clinical use, requiring additional research. The chapter examines psychological and neurobiological mechanisms of action, methodological challenges, and future directions for psychedelic-assisted therapies for PTSD.
Serotonergic psychedelics for depression: A comprehensive overview.
International review of neurobiology January 1, 2025 A M Wingert, C Agnorelli, J Peill et al. 1 citation
Depressive disorders remain a major global challenge, especially with rising treatment-resistant cases. Recent research highlights the antidepressant potential of psilocybin and other 5-HT₂A receptor agonists for major depressive disorder and treatment-resistant depression. Phase I and II clinical trials show that even a single administration can produce rapid and sustained symptom reduction, with effects comparable to conventional treatments like SSRIs and ketamine. Serotonergic psychedelics have a distinctive pharmacological profile and robust safety data, making them promising for patients unresponsive to standard therapies. However, integration into routine practice is hindered by the resource-intensive nature of psychedelic-assisted therapy, requiring specialized training and controlled settings. Some countries, including Australia, Switzerland, and Canada, have begun allowing psilocybin use for treatment-resistant depression.
Human neuroimaging: fMRI.
International review of neurobiology January 1, 2025 Matthew B Wall, Robin L Carhart-Harris
Functional MRI has been central to recent psychedelic research in healthy and clinical populations. Classic psychedelics such as psilocybin, LSD, and DMT acutely and profoundly disrupt normal resting-state brain connectivity, an effect likely linked to their subjective experiences and longer-term positive emotional impacts. This chapter outlines fMRI methodology and reviews current knowledge from task and resting-state studies in both non-clinical and clinical groups. Current limitations include small datasets and lack of standardization; future work should provide more data, standardize acquisition and analysis, conduct multi-modal imaging, and share data openly. fMRI remains a key tool for understanding psychedelic mechanisms and developing psychedelic-based treatments.
Potential therapeutic effects of psychedelics in small doses: Is there a role for microdosing in psychiatry?
International review of neurobiology January 1, 2025 Iva Totomanova, Eline C H M Haijen, Petra P M Hurks et al.
Small doses of LSD and psilocybin produce subtle acute effects on neural connectivity, brain electrophysiology, blood pressure, sleep duration, pain perception, temporal processing, and mood, and reduce symptoms of depression and obsessive-compulsive behavior in patient samples. Extra-pharmacological factors such as baseline subjective state, expectations, and individual differences in drug metabolism influence treatment outcomes. Controlled microdosing studies suggest potential therapeutic applications, but large-scale clinical trials are still needed.