Jesper L. Kristensen - The Consciousness Library

Hippocampal synaptic transmission and Ca2⁺ signaling are altered by the selective 5-HT2A receptor agonist, 25CN-NBOH.

Neuroscience August 30, 2026 Yang Wang, Sinem Cetinkaya Karaca, Mille Deckmann Rasmussen et al.

Classical psychedelics exert therapeutic effects on affective disorders, with serotonin 5-HT2A receptor activation thought to play a central role. The cellular mechanisms by which 5-HT2A signaling modulates neural circuits remain incompletely understood and may differ across mood-regulating brain regions. While psychedelic actions have been extensively studied in the medial prefrontal cortex,...

DOI: 10.1016/j.neuroscience.2026.08.049 Full text Calcium imaging Hippocampus ca1 Patch-clamp electrophysiology Psychedelics +2

Regarding “The molecular mechanisms through which psilocybin prevents suicide: evidence from network pharmacology and molecular docking analyses”

Translational Psychiatry January 31, 2026 Jesper L. Kristensen

Clinical investigations into the therapeutic actions of psilocybin have been the focus of much attention in recent years as duly cited in the manuscript.The authors of the present manuscript discuss potential targets through which psilocybin may help prevent suicide using computational network pharmacology coupled with molecular docking investigations.Unfortunately, the manuscript contains the...

DOI: 10.1038/s41398-026-03844-7 Full text Psilocybin Hallucinogen Molecular pharmacology Schizophrenia object-oriented programming +1

Psychedelics produce enduring behavioral effects and functional plasticity through mechanisms independent of structural plasticity

Neuropsychopharmacology November 12, 2025 Hannah M. Kramer, Meghan Hibicke, Jason W. Middleton et al. 7 citations

Activation of serotonin 2A (5-HT2A) receptors is thought to underly the long-lasting antidepressant effects of psychedelics such as psilocybin, but beyond that, the molecular and cellular mechanisms involved are not well understood. Recent preclinical studies using mice have primarily examined relatively short time points after psychedelic administration, which does not address the long-lasting...

DOI: 10.1038/s41386-025-02272-3 Full text Psilocybin Neuroplasticity Synaptic plasticity Serotonin +11

The Selective Serotonin 5-HT2A Receptor Agonist (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents

ACS Pharmacology & Translational Science May 29, 2025 Meghan Hibicke, Erik Kaadt, Emil Märcher-Rørsted et al. 3 citations

Psychedelics have emerged as a promising treatment for mental health disease, and the therapeutic potential of psilocybin and lysergic acid diethylamide (LSD) is presently being pursued in numerous clinical trials. This has prompted a search for novel agents with more specific pharmacological activities than the rather promiscuous classical psychedelics. Here we present the detailed...

DOI: 10.1021/acsptsci.5c00208 Serotonin Antidepressant Piperidine Agonist +3

The Selective 5HT2A Receptor Agonist, 25CN-NBOH Exerts Excitatory and Inhibitory Cellular Actions on Mouse Medial Prefrontal Cortical Neurons.

Synapse (New York, N.Y.) March 1, 2025 Yang Wang, Jesper L. Kristensen, Kristi A. Kohlmeier 5 citations

Psychedelic compounds have gained renewed interest due to their rapid and long-lasting therapeutic effects on stress-related disorders. While the underlying mechanisms of therapeutic actions of psychedelic compounds are still unclear, these drugs are thought to modulate the activity of the serotonergic system, primarily through activating serotonin type 2A receptor (5-HT2AR) and studies have...

DOI: 10.1002/syn.70014 Full text Serotonin Action potential Brain slices Electrophysiological recordings +1

Discovery and Structure–Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists

Journal of Medicinal Chemistry April 22, 2024 Karla Frydenvang, Emil Märcher-Rørsted, Anders A. Jensen et al. 7 citations

Classical psychedelics such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT) are showing promising results in clinical trials for a range of psychiatric indications, including depression, anxiety, and substance abuse disorder. These compounds are characterized by broad pharmacological activity profiles, and while the acute mind-altering effects can be ascribed...

DOI: 10.1021/acs.jmedchem.4c00082 Pharmacology 5-HT Receptor Structure–activity relationship Serotonin agonist +1

The selective 5-HT2A receptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

bioRxiv Preprint Server April 19, 2024 Anders A. Jensen, Cláudia R. Cecchi, Meghan Hibicke et al. preprint

Psychedelic-assisted psychotherapy has over the last decade emerged as a promising treatment strategy for mental health disease, and the therapeutic potential in classical psychedelics such as psilocybin, LSD and 5-MeO-DMT is presently being pursued in a plethora of clinical trials. However, the resurgent interest in the drugs as therapeutics has also prompted a search for novel agents with...

DOI: 10.1101/2024.04.19.590212 Full text

Structure-Activity Assessment and In-Depth Analysis of Biased Agonism in a Set of Phenylalkylamine 5-HT2A Receptor Agonists.

ACS Chemical Neuroscience August 2, 2023 Eline Pottie, Christian B M Poulie, Icaro A Simon et al. 25 citations

Serotonergic psychedelics are described to have activation of the serotonin 2A receptor (5-HT2A) as their main pharmacological action. Despite their relevance, the molecular mechanisms underlying the psychedelic effects induced by certain 5-HT2A agonists remain elusive. One of the proposed hypotheses is the occurrence of biased agonism, defined as the preferential activation of certain...

DOI: 10.1021/acschemneuro.3c00267 Full text 5-ht2a Biased agonism In vitro pharmacology Minigαq +6

Animal Behavior in Psychedelic Research.

Pharmacological Reviews October 1, 2022 Anna U. Odland, Jesper L. Kristensen, Jesper T. Andreasen 23 citations

Psychedelic-assisted psychotherapy holds great promise in the treatment of mental health disorders. Research into 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelic compounds has increased dramatically over the past two decades. In humans, these compounds produce drastic effects on consciousness, and their therapeutic potential relates to changes in the processing of emotional,...

DOI: 10.1124/pharmrev.122.000590 Full text Psychedelics Animal-behavior Behavioral-research Therapeutic-compounds

Discovery of β-Arrestin-Biased 25CN-NBOH-Derived 5-HT2A Receptor Agonists.

Journal of Medicinal Chemistry September 22, 2022 Christian B M Poulie, Eline Pottie, Icaro A Simon et al. 32 citations

The serotonin 2A receptor (5-HT2AR) is the mediator of the psychedelic effects of serotonergic psychedelics, which have shown promising results in clinical studies for several neuropsychiatric indications. The 5-HT2AR is able to signal through the Gαq and β-arrestin effector proteins, but it is currently not known how the different signaling pathways contribute to the therapeutic effects...

DOI: 10.1021/acs.jmedchem.2c00702 Full text Psychedelic-medicine Pharmacology Mental-health Serotonin-research

The Alkaloids from Lophophora diffusa and Other "False Peyotes".

Journal of Natural Products August 27, 2021 Camilla B Chan, Christian B M Poulie, Simon S Wismann et al. 13 citations

Commonly, false peyote refers to Lophophora diffusa. However, several other unrelated cacti go by this colloquial name. They either resemble "true" peyote, Lophophora williamsii, or are found in similar habitats. To date, over 40 different alkaloids have been isolated from the Lophophora genus. Of these, only the pharmacological actions of mescaline (1) have been extensively investigated. The...

DOI: 10.1021/acs.jnatprod.1c00381 Full text

Investigating the role of 5-HT2A and 5-HT2C receptor activation in the effects of psilocybin, DOI, and citalopram on marble burying in mice

Behavioural Brain Research December 28, 2020 Anna U. Odland, Jesper L. Kristensen, Jesper T. Andreasen 60 citations

Psychedelic drugs acting as 5-hydroxyptryptamine 2A receptor (5-HT2AR) agonists have shown promise as viable treatments of psychiatric disorders, including obsessive-compulsive disorder. The marble burying test is a test of compulsive-like behavior in mice, and psychedelics acting as 5-HT2AR agonists can reduce digging in this test. We assessed the 5-HT2R contribution to the mechanisms of two...

DOI: 10.1016/j.bbr.2020.113093 Psilocybin Citalopram Hallucinogen Pharmacology +3

Investigation of the 2,5-Dimethoxy Motif in Phenethylamine Serotonin 2A Receptor Agonists.

ACS Chemical Neuroscience May 6, 2020 Emil Märcher-Rørsted, Adam L. Halberstadt, Adam K. Klein et al. 20 citations

The 2,5-dimethoxyphenethylamine (2,5-PEA) scaffold is recognized as a motif conferring potent agonist activity at the serotonin 2A receptor (5-HT2AR). The 2,5-dimethoxy motif is present in several classical phenethylamine psychedelics such as 2,4,5- trimethoxyamphetamine (TMA-2), 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5- dimethoxy-4-bromoamphetamine...

DOI: 10.1021/acschemneuro.0c00129 Full text Phenethylamine Agonists Serotonin 2a receptor Structure−activity relationship +2

The selective 5-HT2A receptor agonist 25CN-NBOH: structure-activity relationship, in vivo pharmacology, and in vitro and ex vivo binding characteristics of [3H]25CN-NBOH.

Biochemical Pharmacology April 13, 2020 A. Jensen, Adam L. Halberstadt, Emil Märcher-Rørsted et al. 25 citations

The remarkable effects exhibited by classical psychedelics in recent clinical trials have spawned considerable interest in 5-HT2A receptor (5-HT2AR) activation as a treatment strategy for several psychiatric/cognitive disorders. In this study we have continued our development of 25CN-NBOH, one of the most 5-HT2AR-selective agonists reported to date, as a pharmacological tool for exploration of...

DOI: 10.1016/j.bcp.2020.113979

DARK Classics in Chemical Neuroscience: NBOMes

ACS Chemical Neuroscience October 28, 2019 Christian B M Poulie, Anders A. Jensen, Adam L. Halberstadt et al. 63 citations

N-Benzylphenethylamines, commonly known as NBOMes, are synthetic psychedelic compounds derived from the phenethylamine class of psychedelics (2C-X compounds), which originally have been derived from the naturally occurring alkaloid mescaline. Analogously to their parent compounds and other classical psychedelics, such as psilocybin and lysergic acid diethylamide (LSD), NBOMes are believed to...

DOI: 10.1021/acschemneuro.9b00528 Full text Clinical neuroscience Cognitive neuroscience Cognitive science

5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism.

ACS Chemical Neuroscience November 16, 2016 Sebastian Leth-Petersen, Ida N Petersen, Anders A. Jensen et al.

The toxic hallucinogen 25B-NBOMe is very rapidly degraded by human liver microsomes and has low oral bioavailability. Herein we report on the synthesis, microsomal stability, and 5-HT2A/5-HT2C receptor profile of novel analogues of 25B-NBOMe modified at the primary site of metabolism. Although microsomal stability could be increased while maintaining potent 5-HT2 receptor agonist properties,...

DOI: 10.1021/acschemneuro.6b00265 Full text 5-ht2a receptor agonists Phenethylamines Hallucinogens Microsomal stability

Metabolic Fate of Hallucinogenic NBOMes

Chemical Research in Toxicology December 16, 2015 Sebastian Leth-Petersen, Charlotte Gabel‐Jensen, Nic Gillings et al. 43 citations

2,5-Dimethoxy-N-benzylphenethylamines (NBOMes) are very potent 5-HT2AR agonists. Illicit use of these psychedelic compounds has emerged in recent years, and several fatalities have been linked to their recreational use. In its [(11)C]-labeled form, one NBOMe (25B-NBOMe) was recently developed as a PET-ligand for clinical investigations of 5HT2AR ([(11)C]Cimbi-36). Herein, we have identified the...

DOI: 10.1021/acs.chemrestox.5b00450 Hallucinogen Pharmacology

Serotonin 2A Receptor Agonist Binding in the Human Brain with [11C]Cimbi-36

Journal of Cerebral Blood Flow & Metabolism April 30, 2014 Anders Ettrup, Sofi Da Cunha‐bang, Brenda Mcmahon et al. 106 citations

[ 11 C]Cimbi-36 was recently developed as a selective serotonin 2A (5-HT 2A ) receptor agonist radioligand for positron emission tomography (PET) brain imaging. Such an agonist PET radioligand may provide a novel, and more functional, measure of the serotonergic system and agonist binding is more likely than antagonist binding to reflect 5-HT levels in vivo. Here, we show data from a...

DOI: 10.1038/jcbfm.2014.68 Serotonin agonist Human brain 5-HT Receptor Endocrinology +1

Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists.

ACS Chemical Neuroscience March 19, 2014 Martin Hansen, Karina Phonekeo, James S Paine et al. 125 citations

N-Benzyl substitution of 5-HT2A receptor agonists of the phenethylamine structural class of psychedelics (such as 4-bromo-2,5-dimethoxyphenethylamine, often referred to as 2C-B) confer a significant increase in binding affinity as well as functional activity of the receptor. We have prepared a series of 48 compounds with structural variations in both the phenethylamine and N-benzyl part of the...

DOI: 10.1021/cn400216u Full text Receptor pharmacology Medicinal chemistry Serotonin receptors Drug discovery

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