ACS Pharmacology & Translational Science - The Consciousness Library

Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice

ACS Pharmacology & Translational Science August 2, 2023 Zarmeen Zahid, Zhen Zheng, N. Jones et al. 50 citations

While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course of anxious responsiveness remains unclear. Using rodents, both time-bound...

DOI: 10.1021/acsptsci.3c00123 Psilocybin Anxiolytic Corticosterone Antagonist +5

Receptor Binding Profiles for Tryptamine Psychedelics and Effects of 4-Propionoxy-N,N-dimethyltryptamine in Mice

ACS Pharmacology & Translational Science March 10, 2023 Marilyn Naeem, Grant C. Glatfelter, Duyen N. K. Pham et al. 25 citations

Analogues of 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) are being sold on recreational drug markets and developed as potential medications for psychedelic-assisted therapies. Many of these tryptamine-based psilocybin analogues produce psychedelic-like effects in rodents and humans primarily by agonist activity at serotonin 2A receptors (5-HT2A). However, the comprehensive...

DOI: 10.1021/acsptsci.2c00222 Full text Pharmacology Tryptamines Stereochemistry

Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice

ACS Pharmacology & Translational Science November 2, 2022 Eline Pottie, Marilyn Naeem, Vamshikrishna Reddy Sammeta et al. 91 citations

4-Phosphoryloxy-N,N-dimethyltryptamine (psilocybin) is a naturally occurring tertiary amine found in many mushroom species. Psilocybin is a prodrug for 4-hydroxy-N,N-dimethyltryptamine (psilocin), which induces psychedelic effects via agonist activity at the serotonin (5-HT) 2A receptor (5-HT2A). Several other 4-position ring-substituted tryptamines are present in psilocybin-containing...

DOI: 10.1021/acsptsci.2c00177 Full text Psilocybin Serotonin Pharmacology Tryptamines +6

Automated Computer Software Assessment of 5-Hydroxytryptamine 2A Receptor-Mediated Head Twitch Responses from Video Recordings of Mice

ACS Pharmacology & Translational Science April 8, 2022 Grant C. Glatfelter, Michael R. Chojnacki, Shelby A. McGriff et al. 18 citations

Psychedelics are a class of drugs that produce unique subjective effects via agonist actions at the 5-hydroxytryptamine 2A receptor (5-HT2A). The 5-HT2A-mediated head twitch response (HTR) in rodents is used as a reliable proxy for psychedelic drug activity in humans, but existing methods for measuring HTRs require surgery or time-consuming visual scoring. In the present work, we validated a...

DOI: 10.1021/acsptsci.1c00237 Full text Head geology

Working with Weirdness: A Response to “Moving Past Mysticism in Psychedelic Science”

ACS Pharmacology & Translational Science July 16, 2021 Joost J. Breeksema, Michiel van Elk 69 citations

In response to a recent call to rid psychedelic science of the concept of mystical experience, we argue that acknowledging the varieties and weirdness of psychedelic experiences should be at the heart of any research program on this topic. We highlight the rich tradition and scientific tools for studying mystical-type experiences, their relevance for understanding the therapeutic effects of...

DOI: 10.1021/acsptsci.1c00149

Correction to Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy.

ACS Pharmacology & Translational Science June 11, 2021 Justin C Strickland, Albert Garcia‐romeu, Matthew W Johnson correction

[This corrects the article DOI: 10.1021/acsptsci.0c00187.].

DOI: 10.1021/acsptsci.1c00119 Full text

Moving Past Mysticism in Psychedelic Science

ACS Pharmacology & Translational Science May 4, 2021 James W. Sanders, Josjan Zijlmans 94 citations

The mysticism framework is used to describe psychedelic experiences and explain the effects of psychedelic therapies. We discuss risks and difficulties stemming from the scientific use of a framework associated with supernatural or nonempirical belief systems and encourage researchers to mitigate these risks with a demystified model of the psychedelic state.

DOI: 10.1021/acsptsci.1c00097 Mysticism Epistemology Literature

Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes.

ACS Pharmacology & Translational Science April 9, 2021 Gabrielle Agin-Liebes, Trevor F Haas, Rafael Lancelotta et al. 121 citations

Mescaline is a naturally occurring psychoactive alkaloid that has been used as a sacrament by Indigenous populations in spiritual ritual and healing ceremonies for millennia. Despite promising early preliminary research and favorable anecdotal reports, there is limited research investigating mescaline's psychotherapeutic potential. We administered an anonymous online questionnaire to adults (N...

DOI: 10.1021/acsptsci.1c00018 Full text

Consciousness, Religion, and Gurus: Pitfalls of Psychedelic Medicine.

ACS Pharmacology & Translational Science April 9, 2021 Matthew W. Johnson 109 citations

This viewpoint identifies pitfalls in the study of psychedelic compounds, including those that pose challenges for the potential use of psychedelics as medicines. They are as follows: (1) Sloppiness regarding use of the term "consciousness". (2) Inappropriate introduction of religious/spiritual beliefs of investigators or clinicians. (3) Clinical boundaries and other ethical challenges...

DOI: 10.1021/acsptsci.0c00198 Full text

Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore.

ACS Pharmacology & Translational Science April 9, 2021 Thomas W. Flanagan, Gerald Billac, Alexus N. Landry et al. 50 citations

Psychedelic drugs can exert potent anti-inflammatory effects. However, anti-inflammatory effects do not appear to correlate with behavioral activity, suggesting different underlying mechanisms. We hypothesized that the distinct structural features of psychedelics underlie functionally selective mechanisms at the target 5-HT2A receptor to elicit maximal anti-inflammatory effects. In order to...

DOI: 10.1021/acsptsci.0c00063 Full text 5-ht2a receptor Inflammation reduction Inflammation suppression Anti-inflammatory effects +24

Tropane-Based Ibogaine Analog Rescues Folding-Deficient Serotonin and Dopamine Transporters.

ACS Pharmacology & Translational Science April 9, 2021 Shreyas Bhat, Daryl A. Guthrie, Ameya Kasture et al. 37 citations

Missense mutations that give rise to protein misfolding are rare, but collectively, defective protein folding diseases are consequential. Folding deficiencies are amenable to pharmacological correction (pharmacochaperoning), but the underlying mechanisms remain enigmatic. Ibogaine and its active metabolite noribogaine correct folding defects in the dopamine transporter (DAT), but they rescue...

DOI: 10.1021/acsptsci.0c00102 Full text Protein misfolding Protein folding diseases Proteinopathy Proteostasis +15

EEG Gamma Band Alterations and REM-like Traits Underpin the Acute Effect of the Atypical Psychedelic Ibogaine in the Rat.

ACS Pharmacology & Translational Science April 9, 2021 Joaquín González, Matías Cavelli, Santiago Castro-Zaballa et al. 26 citations

Ibogaine is a psychedelic alkaloid that has attracted large scientific interest because of its antiaddictive properties in observational studies in humans as well as in animal models. Its subjective effect has been described as intense, vivid dream-like experiences occurring while awake; hence, ibogaine is often referred to as an oneirogenic psychedelic. While this unique dream-like profile has...

DOI: 10.1021/acsptsci.0c00164 Full text Anti-addictive potential Waking dream Dream-like effects Vivid effects +13

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

ACS Pharmacology & Translational Science March 18, 2021 Stephen Ross, Gabrielle Agin-Liebes, Sharon L. Lo et al. 133 citations

People with advanced cancer are at heightened risk of desire for hastened death (DHD), suicidal ideation (SI), and completed suicide. Loss of Meaning (LoM), a component of demoralization, can be elevated by a cancer diagnosis and predicts DHD and SI in this population. We completed a randomized controlled trial in which psilocybin-assisted psychotherapy (PAP) produced rapid and sustained...

DOI: 10.1021/acsptsci.1c00020 Full text Psilocybin Suicide prevention Suicidal ideation Distress +10

On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review

ACS Pharmacology & Translational Science March 11, 2021 Richard J. Zeifman, Nikhita Singhal, Leah Breslow et al. 60 citations

Use of classic psychedelics (e.g., psilocybin, ayahuasca, and lysergic acid diethylamide) is increasing, and psychedelic therapy is receiving growing attention as a novel mental health intervention. Suicidality remains a potential safety concern associated with classic psychedelics and is, concurrently, a mental health concern that psychedelic therapy may show promise in targeting. Accordingly,...

DOI: 10.1021/acsptsci.1c00024 Full text Psilocybin Lysergic acid diethylamide Clinical psychology Mental health +4

Serotonin 2A Receptor (5-HT2AR) Activation by 25H-NBOMe Positional Isomers: In Vitro Functional Evaluation and Molecular Docking.

ACS Pharmacology & Translational Science February 25, 2021 Eline Pottie, Olga V. Kupriyanova, Asher L. Brandt et al.

Serotonergic psychedelics are defined as compounds having serotonin 2A receptor (5-HT2AR) activation as an important pharmacological mechanism. These compounds include the phenylalkylamine class, containing substances with e.g. 2C-X structures (phenethylamines) or their N-methoxybenzyl analogues (NBOMes). Besides their abuse potential, psychedelics are increasingly recognized for having...

DOI: 10.1021/acsptsci.0c00189 Full text

Ethical Concerns about Psilocybin Intellectual Property

ACS Pharmacology & Translational Science 2021 Konstantin Gerber, Inti García Flores, Angela Christina Ruiz et al. 54 citations

Since a 1957 exposé in Life Magazine, chemical compounds derived from Psilocybe mushrooms have been the focus of dozens of attempted and successful patents, most recently to treat depression. Regrettably, the Mazatec indigenous communities who stewarded these traditional medicines for millenia are not party to any of these patents, despite a number of international treaties asserting indigenous...

DOI: 10.1021/acsptsci.0c00171 Psilocybin Indigenous Intellectual property Environmental ethics +4

Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy

ACS Pharmacology & Translational Science December 29, 2020 Justin C Strickland, Albert Garcia‐romeu, Matthew W. Johnson 89 citations

Mounting evidence supports the serotonin 2A receptor agonist psilocybin as a psychiatric pharmacotherapy. Little research has experimentally examined how session "set and setting" impacts subjective and therapeutic effects. We analyzed the effects of the musical genre played during sessions of a psilocybin study for tobacco smoking cessation. Participants (N = 10) received psilocybin (20-30...

DOI: 10.1021/acsptsci.0c00187 Full text Psilocybin Musical Music therapy Overtone +2

Discriminative Stimulus Effects of Substituted Tryptamines in Rats

ACS Pharmacology & Translational Science December 29, 2020 Michael B. Gatch, Adam C. Hoch, Theresa M. Carbonaro 13 citations

Novel synthetic compounds have been available for decades as quasi-legal alternatives to controlled substances. The hallucinogen-like effects of eight novel substituted tryptamines were evaluated to determine their potential abuse liability. Male Sprague-Dawley rats were trained to discriminate 2,5-dimethoxy-4-methylamphetamine (DOM, 0.5 mg/kg, i.p., 30 min) from saline....

DOI: 10.1021/acsptsci.0c00173 Full text Tryptamines Stimulus control Hallucinogen Abuse liability +3

Investigation of the Structure–Activity Relationships of Psilocybin Analogues

ACS Pharmacology & Translational Science December 14, 2020 Adam K. Klein, Muhammad Chatha, Lauren J. Laskowski et al. 103 citations

The 5-HT2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and other serotonergic hallucinogens (psychedelic drugs). Although a large amount of experimental work has been conducted to characterize the pharmacology of psilocybin and its dephosphorylated metabolite psilocin (4-hydroxy-N,N-dimethyltryptamine), there has been little systematic...

DOI: 10.1021/acsptsci.0c00176 Full text Psilocybin Serotonin Tryptamines Hallucinogen +8

The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects

ACS Pharmacology & Translational Science December 10, 2020 David E. Olson 328 citations

Psychedelics represent one of the most promising classes of experimental medicines for the treatment of neuropsychiatric disorders due to their ability to promote neural plasticity and produce both rapid and sustained therapeutic effects following a single administration. Conventional wisdom holds that peak mystical experiences induced by psychedelics are a critical component of their...

DOI: 10.1021/acsptsci.0c00192 Full text

Psilocybin-Assisted Group Therapy and Attachment: Observed Reduction in Attachment Anxiety and Influences of Attachment Insecurity on the Psilocybin Experience

ACS Pharmacology & Translational Science December 9, 2020 Christopher S. Stauffer, B. Anderson, Kile Ortigo et al. 65 citations

Attachment insecurity is determined early in life, is a risk factor for psychopathology, and can be measured on two separate continuous dimensions: attachment anxiety and attachment avoidance. Therapeutic changes toward more secure attachment correlate with reduction in psychiatric symptoms. Psilocybin-assisted psychotherapy has demonstrated promise in the treatment of psychopathology, such as...

DOI: 10.1021/acsptsci.0c00169 Full text Psilocybin Anxiety Psychopathology Attachment theory +3

Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth

ACS Pharmacology & Translational Science September 11, 2020 Calvin Ly, Alexandra C. Greb, Maxemiliano V. Vargas et al. 127 citations

Cortical neuron atrophy is a hallmark of depression and includes neurite retraction, dendritic spine loss, and decreased synaptic density. Psychoplastogens, small molecules capable of rapidly promoting cortical neuron growth, have been hypothesized to produce long-lasting positive effects on behavior by rectifying these deleterious structural and functional changes. Here we demonstrate that...

DOI: 10.1021/acsptsci.0c00065 Full text Stimulation Ampa receptor Neurite Cortical neurons +1

Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers

ACS Pharmacology & Translational Science August 31, 2020 Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al. 134 citations

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 (5, 10, and 20 μg) on...

DOI: 10.1021/acsptsci.0c00099 Neuroplasticity Placebo Plasma levels Blood plasma +2

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