Psychedelic Science Newsletter - 2024 February

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3 Mar

Science in Sixty Seconds

Mapping the Mind with EEG

Electroencephalography (EEG) is a non-invasive neuroimaging technique that measures the brain’s electrical activity. It records neuronal firing through electrodes on the scalp and generates distinct wave patterns that mirror various aspects of brain function and cognitive processes. EEG's millisecond-level precision provides a real-time, dynamic view of brain activity, making it an invaluable tool in both clinical and research settings.

EEG in Psychiatry

EEG is increasingly valuable in neuropsychiatry, aiding in the diagnosis and treatment of conditions like epilepsy, depression, and ADHD. It holds immense promise as a biomarker as it can pinpoint unique neural patterns associated with different disorders, even distinguishing between subtypes [1,2]. This capability extends to monitoring disease progression and treatment response, including distinguishing between treatment and placebo effects [3,4,5]. Consequently, EEG enables treatment customization based on individual patient profiles, paving the way for a new era of personalized medicine in neuropsychiatry.

Insights into Psychedelic Actions

EEG research is significantly advancing our understanding of how psychedelics influence the human brain. Here are several key findings:

Disruption of Normal Brainwave Patterns: Psychedelics disrupt typical brainwave patterns, indicating that the brain is entering a unique functional state.
Alterations in Brain Connectivity [6]: Psychedelics promote hyperconnectivity and increased entropy across the brain, This allows for greater communication between different areas and networks, particularly those associated with higher-level functions like imagination. This hyperconnected state may underpin the changes in consciousness and perception associated with psychedelic experiences.
Increased Neuroplasticity [7]: One major finding is the sustained increase in theta power following psilocybin administration. Theta waves, associated with relaxation, creativity, meditation, and dreaming, are indicators of neuroplasticity. Their increase implies that psychedelics might promote neural flexibility, potentially leading to lasting changes in brain function.
Correlation with Symptom Improvement [7]: The increase in EEG theta power post-psilocybin administration correlated with improvements in depression symptoms. This suggests a direct link between the changes in brain activity induced by psychedelics and their potential therapeutic effects.
Cross-species Similarities [8,9]: The EEG patterns elicited by psychedelics in animals closely resemble those observed in human studies, indicating strong translational validity and hinting at a consistent cross-species mechanism of action.

EEG is helping drive significant advancements in neuroscience by providing real-time insights into the intricate workings of the human mind. As technology advances, so too will our understanding of brain function. This will not only provide enhanced insights into underlying psychedelic mechanisms but also opens doors to pioneering novel treatments for various neuropsychiatric disorders.

RESEARCH UPDATES

Psychedelic Clinical Research

Flexible Dosing of Psilocybin for Complex Treatment-Resistant Depression | This randomized clinical trial demonstrates the feasibility and preliminary efficacy of a flexible dosing schedule of psilocybin in individuals with severely treatment-resistant depression, including those with co-morbid conditions or bipolar II disorder (N=30). Repeated doses were associated with enhanced reduction in depression severity | Med

ADHD Brains Altered in 5-HT2A-rich Regions | Neuroimaging study reveals that children with ADHD exhibit altered cortical brain activity in areas associated with GABA and 5-HT2A receptors, offering new insights into the neurobiological mechanisms of ADHD. | Psychiatry and Clinical Neurosciences

5-HT2A as a Biomarker for Multiple Sclerosis | Serum auto-antibodies against 5-HT2A receptor subtype were identified as highly sensitive and specific markers for diagnosing multiple sclerosis (MS); study using ELISA assay analysis of 208 control samples and 104 MS patient samples | Int J Mol Sci

Predicting Psilocybin Therapy Outcomes – fMRI | Using machine learning to analyze fMRI data, researchers found that baseline functional connectivity in certain brain networks can predict the treatment outcomes of psilocybin therapy for depression with high accuracy. Data from two trials (N=16 and N=22). | Journal of Affective Disorders

5-HT2A Gene Linked to Internet Addiction | This study identifies a link between Internet Addiction Disorder and a polymorphism in the 5-HT2A receptor gene (N=40), suggesting a genetic predisposition to this disorder. | Frontiers in Psychiatry

Psychedelics Enhance Sexual Function| Psychedelics potentially improve self-reported sexual satisfaction and functioning. Findings from a mixed-methods study combining data from a large naturalistic study and a smaller, controlled clinical trial | Scientific Reports

Ethnic Disparities in Depression Treatment | A study of treatment-resistant depression in the UK reveals significant differences in treatment pathways and antidepressant prescriptions between ethnic groups, with White patients receiving more antidepressant treatments than the Black, Asian, and Minority Ethnic (BAME) group. | Journal of Affective Disorders

Microdosing vs. Medication for ADHD | A naturalistic study reports that microdosing reduced self-reported ADHD symptoms and improved emotion regulation, more than conventional medications, in adults with severe ADHD (N=66). | European Psychiatry

Psilocybin Exposures Among Youth in the US | The study reveals a significant increase in psilocybin exposures among adolescents and young adults reported to US poison centers. After no significant changes in the number of cases during 2013-2018, cases began to increase in 2019. In 2022 cases more than tripled among adolescents and more than doubled among young adults, compared to 2018. | Journal of Adolescent Health

Young Adults Microdosing | Among young adults in Southern California, 12% were aware of microdosing and 3% had experience with it, primarily using psilocybin and LSD. White race, male gender, bisexuality, prior drug use, ADHD symptoms, mindfulness, and sensation-seeking were associated with microdosing. | Journal of Psychoactive Drugs

Psychedelic Preclinical Research

Psilocybin vs. Mushroom Extract Effects in Mice | A study comparing chemically synthesized psilocybin and psychedelic mushroom extract in mice reveals that the mushroom extract had a more potent and prolonged effect on neuroplasticity-related synaptic proteins and distinct frontal cortex metabolic profiles. | Molecular Psychiatry

Serotonin and Dopamine in ADHD Treatment | Manipulating serotonergic and alpha-2 adrenergic receptors (with a 5-HT1A agonist, 5-HT2A antagonist, alpha-2 agonist) reduced ADHD symptoms in a rat model. The positive effects were associated with upregulation of 5-HT2A receptors and differential expression of dopamine receptors in various brain regions. | International Journal of Molecular Sciences

Serotonin's Role in Prefrontal Cortex Development | Increased serotonin release in the developing prefrontal cortex of mice enhances synaptic density and strength of excitatory synapses; via 5-HT2A and 5-HT7 receptors and independent of glutamatergic activity. | Nature Communications

Psilocybin's Cytotoxic and Anti-inflammatory Effects | Psilocin demonstrates anti-inflammatory properties in activated murine macrophages, suggesting potential therapeutic uses beyond its psychedelic effects. Psilocybin was almost twice as cytotoxic as psilocin. | International Immunopharmacology

5-HT1A Receptors and Stress Vulnerability | Reduced 5-HT1A, but not 5-HT2A, receptor expression in the lateral septum was associated with increased stress vulnerability in mice, and stimulating these receptors reduced stress-induced symptoms | Progress in Neuro-Psychopharmacology and Biological Psychiatry

Structure-Activity Relationships of Phenethylamines | This study reports three validated models for understanding how phenethylamines affect the reuptake of serotonin, dopamine, and norepinephrine through monoamine transporters. | ACS Chemical Neuroscience

Methylone as a Neuroplastogen | Methylone demonstrates rapid-acting neuroplastic effects with higher specificity and fewer off-target effects than MDMA in rats, suggesting its potential in treating PTSD and other neuropsychiatric disorders. | Frontiers in Neuroscience

LSD Microdosing Effects on Zebrafish | Repeated microdoses of LSD did not significantly change anxiety-like behavior, boldness, or locomotion in zebrafish. | Scientific Reports

Serotonergic Receptors x Social Support in Fear Extinction | Blocking different serotonergic receptors in the medial prefrontal cortex shows varied impacts on fear extinction learning in rats depending on the presence of social support. Blocking 5-HT5A and 5-HT6 receptors impaired fear extinction consolidation in the presence of social support, while blocking the 5-HT2A receptor impairs fear extinction when conducted alone. This suggests distinct neuromodulatory processes in social vs. solitary contexts. | Behavioural Brain Research

[Preprint] Psilocybin's Impact on Brain Networks – EEG in Rats | Psilocybin disrupts theta-gamma coupling and alters high gamma and theta connectivity and network density in a dose-dependent manner in rat cortex, with unique effects on different brain regions; EEG recordings from 27 electrodes | bioRxiv

[Preprint] How Psilocybin Alters Fear Extinction | A single dose of psilocybin altered cortical neural activity during fear learning and extinction in mice. Specifically, psilocybin suppressed fear-active neurons and recruited extinction-active neurons and the extent of change was predictive of enhanced fear extinction, suggesting that psilocybin enhances behavioral flexibility by recruiting new populations of neurons. | bioRxiv

Psychedelic Reviews and Commentaries

Psychedelic-Assisted Therapy for People with Gambling Disorder? | The review explores the potential use of psychedelic-assisted therapy (PAT) as a treatment option for gambling disorder, highlighting promising results from recent studies on psychedelic therapy for various mental health and addiction issues and advocating for further research into its effectiveness for gambling disorder. J Behav Addict

Effects Of Hallucinogenic Drugs On The Human Heart | The review examines the effects of various psychedelics – including bufotenin, psilocin, psilocybin, LSD, ergotamine, ergometrine, DMT, and 5-MeO-DMT – on the human heart. Specifically, it examines inotropic (the force of contraction of the heart muscle) and chronotropic (how fast the heart beats), providing insights on potential cardiac effects. Front Pharmacol

Expectancy Effects In Psychedelic Trials | This review discusses the impact of participant expectations on psychedelic trials, covering how expectancy is measured, expectancy effects observed in trials, and the potential independent or interactive role of expectancy with drug effects, highlighting the importance of managing expectancy for future psychedelic trials' rigor and generalizability. Biol Psychiatry Cogn Neurosci Neuroimaging

Efficacy And Acceptability Of Psilocybin For Primary Or Secondary Depression: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials | This systematic review and meta-analysis of 10 randomized controlled trials (N=524) found that psilocybin has a significant antidepressant effect with a large effect size (Hedge's g = -0.89) and that therapeutic effects increased with dose. Adverse events were mostly transient but could be serious. Front Psychiatry

Psychedelics Increase Brain Neurotrophic Factor | A systematic review and meta-analysis of 9 studies showing that psychedelic consumption is associated with increased levels of brain-derived neurotrophic factor (BDNF), suggesting enhanced neuroplasticity and neuron growth. | Journal of Psychopharmacology

Altered States And Social Bonds: Effects Of MDMA And Serotonergic Psychedelics On Social Behavior As A Mechanism Underlying Substance-Assisted Therapy | This review explores the prosocial effects of MDMA and serotonergic psychedelics, highlighting differences in their mechanisms and implications for therapeutic interventions, focusing on altered self-image, responses to social reward, responses to negative social input, and social neuroplasticity. Biol Psychiatry Cogn Neurosci Neuroimaging

Multimodal Neuroimaging of the Effect of Serotonergic Psychedelics on the Brain | The review explores the functional changes in the brain following the administration of serotonergic psychedelics like psilocybin, LSD, or DMT using fMRI and PET neuroimaging techniques, aiming to enhance understanding of their neurobiological mechanisms and potential for treating neuropsychiatric illnesses. AJNR Am J Neuroradiol

Psychedelic Clinical Trials Update

A round-up of the latest registered clinical trials investigating psychedelics:

Harmine/DMT | Molecular Imaging Study | Molecular Imaging Study of Harmine/DMT: a Basic Research Approach (HaD-PET). This study will assess acute cerebrometabolic effects of harmine/DMT in healthy volunteers using quantitative FDG-PET - NCT06252506

Psilocybin | Major Depressive Disorder | The Effects of Psilocybin on Self-Focus and Self-Related Processing in Major Depressive Disorder. This open-label functional Magnetic Resonance Imaging (fMRI) study will assess the effects of a single dose of psilocybin on rumination and the neural correlates of rumination in individuals with major depressive disorder - NCT06247839

Psilocybin | OCD | PsilOCD: A Pharmacological-Challenge Feasibility Study. This study will assess the impact of psilocybin on cognitive inflexibility and neural plasticity in a cohort of people with obsessive-compulsive disorder (OCD) - NCT06258031

Ketamine v. Spravato | Treatment-resistant Depression | Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression (TREK). This study will compare the effectiveness of two formulations of ketamine - Spravato® and racemic ketamine in people with treatment-resistant depression. - NCT06278779

PSYLO UPDATES

Next stop, Paris! Psylo is excited to be competing on the world stage at the Hello Tomorrow Global Start-Up Challenge in March.

Among thousands of global applicants, Psylo is honored to be one of seven finalists in the Medical Biotech & Pharmaceuticals track - Thanks to Dr Will Jorgensen, Director Of Medicinal Chemistry, taking first place at the APAC competition!

CEO Joshua Ismin at a UNSW Founders event in Sydney. (Photo courtesy of Anna Kucera.)

Sam Banister, CSO, and Dilara Bahceci, Head of Communications, at the International Society for Research on Psychedelics (ISRP) meeting in New Orleans. This was a great opportunity to network with leading researchers and hear about the latest discoveries.

Sam and Chief of Staff Krista Licata had the pleasure of having lunch with Ian Lau from Kolon in Denver.

Psylo in the Media

Josh Ismin appeared on a panel for What The Health - a great go-to for the latest updates in health, innovation, and tech.
Dr. Mario de la Fuente Revenga, Senior Director of Translational Pharmacology, wrote a letter to the DEA about the rescheduling of DOI, which was featured in Psychedelic Alpha.