Nicholas V. Cozzi - The Consciousness Library

Direct anti-inflammatory actions of N,N -dimethyltryptamine on microglia are revealed by proteomic profiling and receptor pharmacology

bioRxiv (Cold Spring Harbor Laboratory) August 11, 2026 István Pesti, Ágnes Bessenyei, Rita Frank et al. preprint

ABSTRACT N,N -dimethyltryptamine (DMT) is an endogenous psychedelic tryptamine that has recently emerged as a promising therapeutic candidate for acute ischemic stroke. Although DMT consistently reduces infarct size, attenuates neuroinflammation, and improves functional outcome in experimental stroke, the cellular and receptor mechanisms underlying these effects remain poorly understood....

DOI: 10.64898/2026.08.05.742931

Serotonin 2A receptor binding, functional activity, and in vitro metabolism of two trideuteromethoxy 2C-B isotopologues.

Naunyn-Schmiedeberg's archives of pharmacology June 18, 2026 Nicholas V. Cozzi

The aim of this study was to investigate the effects of deuterium substitution on the in vitro pharmacology of the psychedelic drug 2-(4-bromo-2,5-dimethoxyphenyl)ethan-1-amine (2C-B). Two deuterated isotopologues of 2C-B, namely 2-(4-bromo-5-methoxy-2-(methoxy-d3)phenyl)ethan-1-amine (2CB-2OCD3) and 2-(4-bromo-2-methoxy-5-(methoxy-d3)phenyl)ethan-1-amine (2CB-5OCD3), were synthesized and...

DOI: 10.1007/s00210-026-05566-5 Full text 5-ht2a receptor Binding affinity Calcium Deuterium +3

Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial.

Journal of the Neurological Sciences May 15, 2024 Emmanuelle A. D. Schindler, R Andrew Sewell, Christopher Gottschalk et al. 37 citations

In a recent randomized, double-blind, placebo-controlled study, we observed a nonsignificant reduction of attack frequency in cluster headache after pulse administration of psilocybin (10 mg/70 kg, 3 doses, 5 days apart each). We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen. Eligible participants returned to receive a psilocybin pulse...

DOI: 10.1016/j.jns.2024.122993 Full text Psilocybin Magic mushrooms Cluster headache Headache disorders +8

Exploratory investigation of a patient‐informed low‐dose psilocybin pulse regimen in the suppression of cluster headache: Results from a randomized, double‐blind, placebo‐controlled trial

Headache The Journal of Head and Face Pain November 1, 2022 Christina Luddy, Yutong Zhu, Hayley Lindsey et al. 75 citations

Abstract Objective Using a patient‐informed regimen, we conducted an exploratory randomized, double‐blind, placebo‐controlled study to systematically investigate the effects of psilocybin in cluster headache. Background Sustained reductions in cluster headache burden after limited quantities of psilocybin‐containing mushrooms are anecdotally reported, although to date there are no controlled...

DOI: 10.1111/head.14420 Psilocybin Cluster headache Randomized controlled trial Anesthesia +4

Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder.

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology September 1, 2022 Deepak Cyril D'Souza, Shariful A. Syed, L Taylor Flynn et al. 156 citations

There is considerable interest in the therapeutic potential of psychedelic drugs. Dimethyltryptamine (DMT) is a potent, rapid-onset, and short-acting psychedelic drug that has not yet been independently tested for the treatment of depression. The safety, tolerability, and efficacy of intravenous DMT were investigated in treatment-resistant individuals with major depressive disorder (MDD) and...

DOI: 10.1038/s41386-022-01344-y Full text Psychedelic therapy Treatment-resistant depression Depressive disorder Rapid-onset psychedelic +22

Psilocybin: crystal structure solutions enable phase analysis of prior art and recently patented examples

Acta Crystallographica Section C Structural Chemistry December 20, 2021 Alexander M. Sherwood, Robert B. Kargbo, Kristi W. Kaylo et al. 10 citations

Psilocybin {systematic name: 3-[2-(dimethylamino)ethyl]-1 H -indol-4-yl dihydrogen phosphate} is a zwitterionic tryptamine natural product found in numerous species of fungi known for their psychoactive properties. Following its structural elucidation and chemical synthesis in 1959, purified synthetic psilocybin has been evaluated in clinical trials and has shown promise in the treatment of...

DOI: 10.1107/s2053229621013164 Full text

N,N-Dimethyltryptamine attenuates spreading depolarization and restrains neurodegeneration by sigma-1 receptor activation in the ischemic rat brain.

Neuropharmacology July 1, 2021 Írisz Szabó, Viktória É Varga, Szabolcs Dvorácskó et al. 67 citations

Dimethyltryptamine (DMT), an endogenous ligand of sigma-1 receptors (Sig-1Rs), acts against systemic hypoxia, but whether DMT may prevent cerebral ischemic injury is unexplored. Here global forebrain ischemia was created in anesthetized rats and aggravated with the induction of spreading depolarizations (SDs) and subsequent short hypoxia before reperfusion. Drugs (DMT, the selective Sig-1R...

DOI: 10.1016/j.neuropharm.2021.108612 Full text Cerebral ischemia N,N-Dimethyltryptamine Sigma-1 receptor Spreading depolarization +1

Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2021 Emmanuelle A. D. Schindler, R Andrew Sewell, Christopher Gottschalk et al. 138 citations

While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test...

DOI: 10.1007/s13311-020-00962-y Full text Psilocybin Single dose Migraine headache Lasting therapeutic effects +8

Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

ACS Omega July 1, 2020 Jessica Sable, Tura Patterson, Gary Tarpley et al. 41 citations

A second-generation kilogram-scale synthesis of the psychedelic tryptamine psilocybin has been developed. The synthesis was designed to address several challenges first encountered with the scale-up of previously described literature procedures, which were not optimized for providing consistent yield and purity of products, atom economy, or being run in pilot plant-scale reactors. These...

DOI: 10.1021/acsomega.0c02387 Psilocybin Phosphorylation

Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials

Drug Testing and Analysis July 1, 2020 Nicholas V. Cozzi, Paul F. Daley 12 citations

Abstract Since 2006, there has been a resurgent interest in the pharmacology and therapeutics of psychedelic drugs. Psilocybin, the 4‐phosphoryl ester of N,N ‐dimethyltryptamine (DMT), has been studied most often, but DMT itself is also appealing because of its brief but profound psychological effects and its presence as an endogenous substance in mammalian brain. Although there have been a few...

DOI: 10.1002/dta.2889 X-ray powder diffraction Alane Aluminum hydride Pharmaceutical synthesis +12

Receptor binding profiles and behavioral pharmacology of ring-substituted N,N-diallyltryptamine analogs.

Neuropharmacology November 1, 2018 Landon M. Klein, Nicholas V. Cozzi, Paul F. Daley et al. 43 citations

Substantial effort has been devoted toward understanding the psychopharmacological effects of tryptamine hallucinogens, which are thought to be mediated by activation of 5-HT2A and 5-HT1A receptors. Recently, several psychoactive tryptamines based on the N,N-diallyltryptamine (DALT) scaffold have been encountered as recreational drugs. Despite the apparent widespread use of DALT derivatives in...

DOI: 10.1016/j.neuropharm.2018.02.028 Full text 4-aco-dalt 4-Acetoxy-N,N-Diallyltryptamine 4-Hydroxy-N,N-Diallyltryptamine 5-MEO-Dalt +8

High dose psilocybin is associated with positive subjective effects in healthy volunteers

Journal of Psychopharmacology June 27, 2018 Christopher R. Nicholas, Kelsey M. Henriquez, Michele Gassman et al. 85 citations

Aim: The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Methods: Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8–36.6 mg; 27.1–54.0 mg; 36.3–59.2 mg) a minimum of four weeks apart in a...

DOI: 10.1177/0269881118780713 Psilocybin Mysticism Significant difference

Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults

Clinical Pharmacokinetics March 28, 2017 Randall Brown, Christopher R. Nicholas, Nicholas V. Cozzi et al. 189 citations

IntroductionPsilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy...

DOI: 10.1007/s40262-017-0540-6 Psilocybin Pharmacokinetics Pharmacology Urine +2

Receptor binding profiles and quantitative structure-affinity relationships of some 5-substituted-N,N-diallyltryptamines.

Bioorganic & Medicinal Chemistry Letters February 1, 2016 Nicholas V. Cozzi, Paul F. Daley 24 citations

N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive...

DOI: 10.1016/j.bmcl.2015.12.053 Full text 5-Methoxy-N,N-Diallyltryptamine Dalt Hallucinogen Psychopharmacology +9

Synthesis and characterization of 5‐methoxy‐2‐methyl‐N,N‐dialkylated tryptamines

Drug Testing and Analysis 2012 Simon D. Brandt, Ruchanok Tearavarich, Nicola M. Dempster et al. 10 citations

The absence of reference material is a commonly experienced difficulty among medical and forensic professionals tasked with identifying new psychoactive substances that are encountered for the first time. The identification of newly emerging substances lies at the heart of forensic and clinical analysis, and a proactive public health policy calls for a thorough analysis of the properties of new...

DOI: 10.1002/dta.398 Tryptamines Iminium Designer drug Mass spectrometry +6

Microwave‐accelerated preparation and analytical characterization of 5‐ethoxy‐N,N‐dialkyl‐[α,α,β,β‐H4]‐ and [α,α,β,β‐D4]‐tryptamines

Drug Testing and Analysis December 29, 2010 Ruchanok Tearavarich, Viwat Hahnvajanawong, Nicola M. Dempster et al. 10 citations

The increased interest in N,N-dialkyl tryptamines is a reflection of their diverse range of biologically active properties. Deuterated derivatives are of interest for use as internal standards in bioanalytical or pharmacological assays. The present study reports on the synthesis of twelve novel 5-ethoxy-N,N-dialkyl-[α,α,β,β-H(4) ]-tryptamines and their [α,α,β,β-D(4) ]-counterparts following the...

DOI: 10.1002/dta.223 Tryptamines Iminium Tetrahydrofuran Mass spectrometry +7

Dimethyltryptamine and other hallucinogenic tryptamines exhibit substrate behavior at the serotonin uptake transporter and the vesicle monoamine transporter.

J Neural Transm (Vienna) September 12, 2009 Nicholas V. Cozzi, Anupama Gopalakrishnan, Lyndsey L. Anderson et al. 144 citations

N,N-dimethyltryptamine (DMT) is a potent plant hallucinogen that has also been found in human tissues. When ingested, DMT and related N,N-dialkyltryptamines produce an intense hallucinogenic state. Behavioral effects are mediated through various neurochemical mechanisms including activity at sigma-1 and serotonin receptors, modification of monoamine uptake and release, and competition for...

DOI: 10.1007/s00702-009-0308-8 DMT 5-HT Hallucinogens psychedelics Psychoactive compounds +19

The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

Science February 13, 2009 Dominique Fontanilla, Molly Johannessen, Abdol R. Hajipour et al. 528 citations

The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound...

DOI: 10.1126/science.1166127 Full text Sigma-1 receptor Sigma receptor Hallucinogen Pharmacology +6

N,N ‐dialkyltryptamines inhibit plasma membrane and vesicular serotonin transport

The FASEB Journal March 1, 2008 Nicholas V. Cozzi, Anupama Gopalakrishnan, Lyndsey L. Anderson et al.

The plant hallucinogen N,N ‐dimethyltryptamine (DMT) has been used for religious and other purposes for many centuries. Over the past few decades, DMT has been reported in human brain, and pharmacological studies have shown that DMT binds to monoamine receptors. Recently, several N,N ‐dialkyltryptamines were reported to modify monoamine uptake and release in rat brain synaptosomes, indicating...

DOI: 10.1096/fasebj.22.1_supplement.714.10

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