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Psychedelic-Assisted Therapy and Psychedelic Science: A Review and Perspective on Opportunities in Neurosurgery and Neuro-Oncology

NEUROSURGERY (2023)

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Article Neurosciences

Deep Brain Stimulation for Depression Informed by Intracranial Recordings

Sameer A. Sheth et al.

Summary: The success of deep brain stimulation (DBS) in treating Parkinson's disease has led to its application in other disorders, including treatment-resistant depression. However, the inconsistent results of DBS for treatment-resistant depression can be attributed to a lack of understanding of the brain networks regulating mood, especially on an individual level. This study reports the results of the first subject treated with DBS for treatment-resistant depression using an approach that incorporates intracranial recordings to personalize understanding of network behavior and its response to stimulation. The findings demonstrate the feasibility of this personalized platform, which has the potential to improve surgical neuromodulation for various neurological and psychiatric disorders.

BIOLOGICAL PSYCHIATRY (2022)

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Review Clinical Neurology

Models of psychedelic drug action: modulation of cortical-subcortical circuits

Manoj K. Doss et al.

Summary: Classic psychedelic drugs have potential in treating psychiatric disorders, and the involvement of the serotonin 2A receptor and the cerebral cortex is crucial in their action. Different models, including the CSTC model, REBUS model, and CCC model, have been proposed to explain the impact of 5-HT2A activation on neural systems during psychedelic drug effects.

BRAIN (2022)

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Review Medicine, Research & Experimental

Safety and Feasibility of Nucleus Accumbens Surgery for Drug Addiction: A Systematic Review

Paula Alejandra Navarro et al.

Summary: This study conducted a systematic review of 15 studies on NAcc surgery for substance dependence treatment, finding that while available studies report benefits in treating drug addictions with NAcc surgery, further carefully planned prospective studies are needed to address the efficacy and indications.

NEUROMODULATION (2022)

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Review Biochemistry & Molecular Biology

Psychedelic-inspired approaches for treating neurodegenerative disorders

Hannah N. Saeger et al.

Summary: Psychedelics are increasingly recognized for their potential to treat various brain disorders by influencing gene expression, activating neuronal mechanisms, and modulating the immune system. While not yet extended to neurodegenerative disorders, approaches based on psychedelic science may be useful for treating these diseases. The primary target of psychedelics, the 5-HT2A receptor, plays important roles in neuronal health and may have implications for diseases like Alzheimer's and dementia.

JOURNAL OF NEUROCHEMISTRY (2022)

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Article Clinical Neurology

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up

Natalie Gukasyan et al.

Summary: This study demonstrates that psilocybin-assisted therapy can have long-lasting antidepressant effects in patients with moderate to severe depression, as observed over a 12-month period.

JOURNAL OF PSYCHOPHARMACOLOGY (2022)

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Article Psychiatry

Apathy after subarachnoid haemorrhage: A systematic review

Wai Kwong Tang et al.

Summary: This systematic review examines the symptom of apathy after non-traumatic subarachnoid hemorrhage (SAH), including its prevalence, severity, time course, associated factors, and impact on patients' quality of life. The study found that apathy is common after SAH and may be influenced by comorbid cognitive impairment and hydrocephalus. Apathy is associated with reduced participation in leisure and sexual activities. However, there were methodological shortcomings in the included studies, highlighting the need for further research.

JOURNAL OF PSYCHOSOMATIC RESEARCH (2022)

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Review Neurosciences

Serotonin toxicity of serotonergic psychedelics

Benjamin Malcolm et al.

Summary: This review evaluates the risks of serotonin toxicity (ST) when combining psychedelics with available serotonergic pharmacotherapy options, describing signs and symptoms of ST, mechanisms of ST risk, known information about serotonergic psychedelic drug interactions, and potential management strategies. The severity of serotonin-related adverse reactions ranges from serotonin syndrome being the most severe manifestations of ST, and the varying serotonergic mechanisms of psychedelics and psychotropics suggest that some combinations may pose a significant risk for ST while others are likely benign.

PSYCHOPHARMACOLOGY (2022)

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Article Neurosciences

Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects

Friederike Holze et al.

Summary: This study compared the subjective and autonomic effects of LSD and psilocybin, finding that the higher doses of both substances produced similar subjective effects, but psilocybin had weaker effects at a lower dose. Additionally, LSD and psilocybin showed differences in their effects on heart rate and blood pressure.

NEUROPSYCHOPHARMACOLOGY (2022)

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Review Behavioral Sciences

Beating pain with psychedelics: Matter over mind?

Igor Elman et al.

Summary: Research suggests that psychedelic drugs may have potential analgesic effects for chronic pain by reducing physical and emotional pain, restoring neural connectivity, and exerting anti-neuroinflammatory and pro-immunomodulatory actions. However, the use of these drugs raises concerns regarding safety, legality, and ethics. Additional investigation into these areas is needed to further understand the mechanisms of chronic pain and affective disorders, and develop innovative and effective neurobiological-based therapies.

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS (2022)

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Article Psychiatry

Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder A Randomized Clinical Trial

Michael P. Bogenschutz et al.

Summary: This study aimed to evaluate the effects of high-dose psilocybin on patients with AUD. The results showed that psilocybin combined with psychotherapy significantly decreased the percentage of heavy drinking days.

JAMA PSYCHIATRY (2022)

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Review Anesthesiology

More Than 1 in 3 Patients With Chronic Low Back Pain Continue to Use Opioids Long-term After Spinal Fusion A Systematic Review

Matthew L. Vraa et al.

Summary: This systematic review examines the rates of opioid use after lumbar spine fusion. The results show a high proportion of patients using opioids long-term after surgery, but there is a lack of consistent reporting on this outcome in lumbar fusion trials. This limits definitive conclusions about the efficacy of spinal fusion in reducing long-term opioid use.

CLINICAL JOURNAL OF PAIN (2022)

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Review Psychiatry

Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern-era clinical studies

Kristoffer A. A. Andersen et al.

Summary: The systematic review of modern-era clinical studies on serotonergic psychedelics drugs for mental health conditions shows promising treatment efficacy and long-lasting effects in some patients. The safety and feasibility of the studies provide important evidence for the potential of psychedelic therapy as a new treatment avenue for psychiatric conditions.

ACTA PSYCHIATRICA SCANDINAVICA (2021)

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Article Biochemistry & Molecular Biology

A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain

Nakul Ravi Raval et al.

Summary: This study showed that a single dose of psilocybin can lead to increased SV2A density and decreased 5-HT2AR density in the pig brain, suggesting a potential role in the antidepressant effects of psilocybin.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Clinical Neurology

Efficacy and Safety of Intravenous Mesenchymal Stem Cells for Ischemic Stroke

Jong-Won Chung et al.

Summary: This study indicates that autologous MSC treatment did not lead to improvements in 90-day outcomes for patients with chronic stroke, as measured by the mRS score. However, detailed functional analysis did show significant improvement in lower extremity motor function in the MSC group compared to the control group.

NEUROLOGY (2021)

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Review Pharmacology & Pharmacy

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

Antonio Inserra et al.

Summary: Psychedelic compounds are emerging as potential novel therapeutics in psychiatry, with their main effects mediated through the modulation of neurotransmitter systems, immunity, and neuroplasticity. Promising results suggest an opportunity for improvement in the treatment of psychiatric disorders, an area that has seen limited advancement in the past 20 years. Studies are underway to separate the psychedelic effects from the therapeutic effects of these compounds, aiming to provide more effective treatment options.

PHARMACOLOGICAL REVIEWS (2021)

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Article Neurosciences

Depression following traumatic brain injury: a comprehensive overview

Marc Fakhoury et al.

Summary: Traumatic brain injury (TBI) is a major health concern that often leads to long-term complications, with depression being the most common complication. Post-traumatic depression (P-TD) affects around 30% of individuals with TBI, with the majority experiencing symptoms within the first year. The mechanisms and effective treatments for P-TD are still not fully understood.

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Review Psychology, Clinical

Transcranial Magnetic Stimulation: A review about its efficacy in the treatment of alcohol, tobacco and cocaine addiction

Mariangela Antonelli et al.

Summary: Repetitive TMS has shown promising results in patients with alcohol, tobacco, and cocaine use disorder, indicating a potential role in the treatment of SUD.

ADDICTIVE BEHAVIORS (2021)

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The Human Connectome Project: A retrospective

Jennifer Stine Elam et al.

Summary: The Human Connectome Project (HCP) aims to accelerate advances in human neuroimaging by studying a large number of healthy young adults and sharing data and tools. The WU-Minn-Ox consortium has achieved its core objectives and emerged as a set of best-practice strategies for optimizing data acquisition and analysis.

NEUROIMAGE (2021)

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Review Pharmacology & Pharmacy

The Evolved Psychology of Psychedelic Set and Setting: Inferences Regarding the Roles of Shamanism and Entheogenic Ecopsychology

Michael James Winkelman

Summary: This review discusses the impact of shamanism and psychedelics on human evolution, including their effects on the selection of ancient human psychological traits and adaptive mechanisms, as well as the connections between shamanism and psychedelics in terms of natural selection and innate modular thought processes.

FRONTIERS IN PHARMACOLOGY (2021)

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Review Neurosciences

Serotonergic Psychedelics in Neural Plasticity

Kacper Lukasiewicz et al.

Summary: Classical serotonergic psychedelics can induce therapeutic effects by promoting neural plasticity.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2021)

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Review Psychiatry

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

John R. Kelly et al.

Summary: Psychedelic therapy, with its combination of psychopharmacology and psychological support, shows promise as a transdiagnostic treatment strategy for various disorders, particularly depression, treatment resistant depression, and addiction disorders. However, further research is needed to understand the specific clinical dimensions and underlying neurobiological pathways of psychedelics' efficacy.

FRONTIERS IN PSYCHIATRY (2021)

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Article Biochemistry & Molecular Biology

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study

Jennifer M. Mitchell et al.

Summary: The results demonstrate that MDMA-assisted therapy is safe and effective in treating severe post-traumatic stress disorder. Compared with placebo, MDMA significantly reduces CAPS-5 scores and improves functional impairment.

NATURE MEDICINE (2021)

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Article Medicine, General & Internal

Trial of Psilocybin versus Escitalopram for Depression

Robin Carhart-Harris et al.

Summary: The study compared the efficacy of psilocybin and escitalopram in treating patients with major depressive disorder. While there was no significant difference in antidepressant effects between the two drugs at week 6, secondary outcomes generally favored psilocybin over escitalopram, though these results were not adjusted for multiple comparisons. Larger and longer trials are needed to further compare psilocybin with established antidepressants.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Article Psychology, Multidisciplinary

Psychedelics, Sociality, and Human Evolution

Jose Manuel Rodriguez Arce et al.

Summary: The study suggests that our hominin ancestors encountered and possibly ingested psychedelic mushrooms during their evolution, impacting their sociality and adaptability. The use of psychedelics may have helped ancient hominins better adapt to environmental changes and shape the socio-cognitive niche.

FRONTIERS IN PSYCHOLOGY (2021)

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Article Psychiatry

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder A Randomized Clinical Trial

Alan K. Davis et al.

Summary: The study showed that psilocybin therapy with psychological support is effective in treating MDD, building on previous findings in patients with cancer and depression, as well as in a nonrandomized study in patients with treatment-resistant depression.

JAMA PSYCHIATRY (2021)

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Review Rehabilitation

TBI as a Risk Factor for Substance Use Behaviors: A Meta-analysis

J. Davis VanderVeen

Summary: The study revealed a small decrease in substance use behaviors after moderate to severe TBI, while there was no significant change after mild TBI. The findings suggest the importance of accurate assessment to identify individuals at greatest risk for problematic substance use behaviors after TBI.

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2021)

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Article Clinical Neurology

Short- and long-term opioid use in survivors of subarachnoid hemorrhage

Ali Mahta et al.

Summary: Opioids are commonly used for pain management in acute subarachnoid hemorrhage (SAH) patients, but the risk of long-term opioid dependence is unclear. Research showed that some patients continue to use opioids after discharge, and factors such as poor Hunt and Hess grades and intraventricular hemorrhage may influence opioid prescription at discharge.

CLINICAL NEUROLOGY AND NEUROSURGERY (2021)

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Review Pharmacology & Pharmacy

Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics

Lily R. Aleksandrova et al.

Summary: The emerging therapeutic efficacy of ketamine and classical psychedelics for depression has sparked considerable interest in the mechanisms underlying neuroplasticity. Preclinical and clinical evidence suggests that these drugs induce synaptic, structural, and functional changes, particularly in pyramidal neurons in the prefrontal cortex, resulting in adaptive rewiring of pathological neurocircuitry.

TRENDS IN PHARMACOLOGICAL SCIENCES (2021)

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Implication of problematic substance use in poststroke depression: an hospital-based study

Yolaine Rabat et al.

Summary: The study found a significant proportion of stroke patients with problematic substance use, including cannabis users. The prevalence of PSD is high, especially for severe depression. The results suggest that baseline tobacco dependence severity may increase the risk of PSD.

SCIENTIFIC REPORTS (2021)

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Reducing the Cognitive Footprint of Brain Tumor Surgery

Nicholas B. Dadario et al.

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FRONTIERS IN NEUROLOGY (2021)

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Psychedelics for Brain Injury: A Mini-Review

Shariq Mansoor Khan et al.

Summary: Stroke and traumatic brain injury are major causes of disability, but pharmacologic treatment of brain injury is still in its infancy. Recent clinical trials are exploring the potential of psychedelic therapeutics in influencing neuroinflammation, hippocampal neurogenesis, and neuroplasticity to treat brain injury. Further trials will provide insight into how these drugs may impact brain injury treatment, particularly in cases of TBI and reperfusion injury from stroke.

FRONTIERS IN NEUROLOGY (2021)

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Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics

Cato M. H. de Vos et al.

Summary: Clinical studies suggest that psychedelics induce rapid changes in neuroplasticity mechanisms, leading to alterations in gene and protein expression, increased neurotrophic factor levels, and enhanced dendritic complexity. Repeated administration of psychedelics can directly stimulate neurogenesis and elevate BDNF mRNA levels, indicating potential long-lasting effects on brain plasticity. Future research could focus on deciphering specific cellular mechanisms activated by different psychedelics to better understand their therapeutic potential.

FRONTIERS IN PSYCHIATRY (2021)

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Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Gabriele Bonaventura et al.

Summary: Stem cells offer potential therapeutic strategies for severe neurodegenerative disorders by replacing damaged neuronal cells and creating a neuro-protective environment through the release of bioactive molecules. The field of stem cells is advancing with the introduction of new technologies and alternative cell tissue sources, pointing towards exciting frontiers in research for treatment options of these diseases.

CELLS (2021)

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Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer

Stephen Ross et al.

Summary: Psilocybin-assisted psychotherapy (PAP) shows rapid and sustained improvements in depression, demoralization, and hopelessness in cancer patients. Further analysis reveals significant within-group reductions in loss of meaning and suicidal ideation following PAP treatment.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2021)

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Fear of Cancer Recurrence and Death Anxiety: Unaddressed Concerns for Adult Neuro-oncology Patients

Ashlee R. Loughan et al.

Summary: Despite preliminary findings suggesting prevalence of these concerns, primary brain tumor (PBT) patients are considerably underrepresented in existential psycho-oncology literature. Current research findings indicate that existential distress is correlated with heightened depression and anxiety, leading to overall worsened quality of life.

JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS (2021)

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Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects

Friederike Holze et al.

NEUROPSYCHOPHARMACOLOGY (2020)

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Beyond LSD: A Broader Psychedelic Zeitgeist during the Early to Mid-20th Century

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Psilocybin-occasioned mystical-type experience in combination with meditation and other spiritual practices produces enduring positive changes in psychological functioning and in trait measures of prosocial attitudes and behaviors

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Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution

Enzo Tagliazucchi et al.

CURRENT BIOLOGY (2016)

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Article Clinical Neurology

LSD modulates music-induced imagery via changes in parahippocampal connectivity

Mendel Kaelen et al.

EUROPEAN NEUROPSYCHOPHARMACOLOGY (2016)

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Article Clinical Neurology

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

Roland R. Griffiths et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2016)

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Article Clinical Neurology

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial

Stephen Ross et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2016)

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Review Neurosciences

The Human Connectome Project's neuroimaging approach

Matthew F. Glasser et al.

NATURE NEUROSCIENCE (2016)

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Article Neurosciences

LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality

Patrick C. Dolder et al.

NEUROPSYCHOPHARMACOLOGY (2016)

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Article Orthopedics

Recidivism Rates After Smoking Cessation Before Spinal Fusion

Brandon B. Carlson et al.

ORTHOPEDICS (2016)

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Article Multidisciplinary Sciences

Neural correlates of the LSD experience revealed by multimodal neuroimaging

Robin L. Carhart-Harris et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

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Article Clinical Neurology

Classic hallucinogens in the treatment of addictions

Michael P. Bogenschutz et al.

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY (2016)

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Review Clinical Neurology

Anxiety prevalence following spinal cord injury: a meta-analysis

J. Le et al.

SPINAL CORD (2016)

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Review Psychiatry

Novel psychopharmacological therapies for psychiatric disorders: psilocybin and MDMA

Michael C. Mithoefer et al.

LANCET PSYCHIATRY (2016)

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Review Rehabilitation

Prevalence of Depression After Spinal Cord Injury: A Meta-Analysis

Ryan Williams et al.

ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION (2015)

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Article Psychiatry

Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: cohort study using a primary care database

Trevor Hill et al.

BMC PSYCHIATRY (2015)

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Article Neurosciences

Finding the self by losing the self: Neural correlates of ego-dissolution under psilocybin

Alexander V. Lebedev et al.

HUMAN BRAIN MAPPING (2015)

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Article Clinical Neurology

Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin

Frederick S. Barrett et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2015)

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Review Clinical Neurology

Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences?

Tomislav Majic et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2015)

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Article Clinical Neurology

Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study

Michael P. Bogenschutz et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2015)

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Review Anesthesiology

Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis

Kevin E. Vowles et al.

PAIN (2015)

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Article Clinical Neurology

Patients Experience High Levels of Anxiety 2 Years Following Aneurysmal Subarachnoid Hemorrhage

Ann-Christin von Vogelsang et al.

WORLD NEUROSURGERY (2015)

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Article Psychology, Clinical

Indoleamine Hallucinogens in Cluster Headache: Results of the Clusterbusters Medication Use Survey

Emmanuelle A. D. Schindler et al.

JOURNAL OF PSYCHOACTIVE DRUGS (2015)

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Article Clinical Neurology

Predictors of Depression and Anxiety in Patients with Intracranial Neoplasms

Brian S. Appleby et al.

JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES (2014)

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Article Multidisciplinary Sciences

Homological scaffolds of brain functional networks

G. Petri et al.

JOURNAL OF THE ROYAL SOCIETY INTERFACE (2014)

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Letter Psychology, Multidisciplinary

Hallucinogens - don't choose ignorance

Laura Oxley

PSYCHOLOGIST (2014)

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Article Clinical Neurology

Frequency of anxiety after stroke: a systematic review and meta-analysis of observational studies

C. Alexia Campbell Burton et al.

INTERNATIONAL JOURNAL OF STROKE (2013)

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Review Psychology, Clinical

A Multidimensional Approach to Apathy after Traumatic Brain Injury

Annabelle Arnould et al.

NEUROPSYCHOLOGY REVIEW (2013)

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Article Clinical Neurology

Depression in relation to anxiety, obsessionality and phobia among neurosurgical patients with a primary brain tumor: A 1-year follow-up study

Arja Mainio et al.

CLINICAL NEUROLOGY AND NEUROSURGERY (2011)

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Editorial Material Substance Abuse

Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin

Udo Benzenhoefer et al.

ADDICTION (2010)

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Article Neurosciences

OPINION The neurobiology of psychedelic drugs: implications for the treatment of mood disorders

Franz X. Vollenweider et al.

NATURE REVIEWS NEUROSCIENCE (2010)

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Review Clinical Neurology

Human hallucinogen research: guidelines for safety

M. W. Johnson et al.

JOURNAL OF PSYCHOPHARMACOLOGY (2008)

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Article Clinical Neurology

Decreased quality of life and depression as predictors for shorter survival among patients with low-grade gliomas:: a follow-up from 1990 to 2003

Arja Mainio et al.

EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE (2006)

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Article Oncology

Predicting major depression in brain tumor patients

DK Wellisch et al.

PSYCHO-ONCOLOGY (2002)

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