ACS Chemical Neuroscience
March 9, 2021
Grant C. Glatfelter, Donna Walther, Michael Evans‐brown et al.
29 citations
Synthetic cathinones are a class of new psychoactive substances that induce psychostimulant effects and pose risk for hospitalizations, overdose, and death. At the present time, derivatives of the synthetic cathinone, methylone, are being confiscated in nonmedical (i.e., recreational) drug markets worldwide. In particular, eutylone is a newly emerging methylone analog that possesses ethyl...
ACS Chemical Neuroscience
January 5, 2021
M. de la Fuente Revenga, Urjita H. Shah, Nima Nassehi et al.
Known classic psychedelic serotonin 2A receptor (5-HT2AR) agonists retain a tryptamine or phenethylamine at their structural core. However, activation of the 5-HT2AR can be elicited by drugs lacking these fundamental scaffolds. Such is the case of the N-substituted piperazine quipazine. Here, we show that quipazine bound to and activated 5-HT2AR as measured by [3H]ketanserin binding...
ACS Chemical Neuroscience
December 2, 2020
R Bruno Hernández-alvarado, Abraham Madariaga-Mazón, Alfredo Ortega et al.
29 citations
Salvinorin A is the main bioactive compound in Salvia divinorum, an endemic plant with ancestral use by the inhabitants of the Mazateca mountain range (Sierra Mazateca) in Oaxaca, México. The main use of la pastora, as locally known, is in spiritual rites due to its extraordinary hallucinogenic effects. Being the first known nonalkaloidal opioid-mediated psychotropic molecule, salvinorin A set...
ACS Chemical Neuroscience
October 6, 2020
Genís Ona, Rafael G. Dos Santos, Jaime E. C. Hallak et al.
12 citations
Research with psychedelic drugs has mainly focused on isolated compounds. However, this approach is challenged by the "polypharmacology" paradigm. In this Viewpoint, we suggest that we may be missing something if we do not use the whole product in the case of ayahuasca or Psilocybe mushrooms. After describing how research on psychedelic drugs can be effectively combined with the...
ACS Chemical Neuroscience
June 3, 2020
Paola Rodrı Guez, Jessika Urbanavicius, José Pedro Prieto et al.
44 citations
Anecdotal reports and open-label case studies in humans indicated that the psychedelic alkaloid ibogaine exerts profound antiaddictive effects. Ample preclinical evidence demonstrated the efficacy of ibogaine, and its main metabolite, noribogaine, in substance-use-disorder rodent models. In contrast to addiction research, depression-relevant effects of ibogaine or noribogaine in rodents have...
ACS Chemical Neuroscience
May 12, 2020
Kodye L. Abbott, Kristina Gill, Patrick Flannery et al.
7 citations
Modern day research, in an attempt to determine the potential therapeutic and adverse effects of illicit substances, is a growing field, but one that faces many regulatory challenges. Due to the potential abuse of illicit substances such as Cannabis, 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD) and psilocybin, regulations have been conceived with the intent of...
ACS Chemical Neuroscience
May 8, 2020
Rachel S Crowley, Andrew P Riley, Amy F Alder et al.
Previous structure-activity relationship (SAR) studies identified the first centrally-acting, non-nitrogenous μ opioid receptor (MOR) agonist, kurkinorin (1), derived from salvinorin A. In an effort to further probe the physiological effects induced upon activation of MORs with this non-morphine scaffold, a variety of analogues were synthesized and evaluated in vitro for their ability to...
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...
ACS Chemical Neuroscience
April 23, 2020
Hideaki Yano, Pramisha Adhikari, Sett Naing et al.
26 citations
The nonmedical (i.e., recreational) misuse of synthetic cannabinoids (SCs) is a worldwide public health problem. When compared to cannabis, the misuse of SCs is associated with a higher incidence of serious adverse effects, suggesting the possible involvement of noncannabinoid sites of action. Here, we find that, unlike the phytocannabinoid Δ9-tetrahydrocannabinol, the indole-moiety containing...
ACS Chemical Neuroscience
March 5, 2020
Meghan Hibicke, Alexus N. Landry, Hannah M. Kramer et al.
211 citations
Psilocybin shows efficacy to alleviate depression in human clinical trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of...
ACS Chemical Neuroscience
February 3, 2020
Jinghua Zhao, XueJie Liu, Daiyue Chang et al.
About 16% of the world's population has major depressive disorder. Traditional antidepressants have slow effect rates and low response rates. Many studies have shown that low doses of ketamine can produce rapid and effective antidepressant effects. However, its mechanism of action needs further exploration. Lipopolysaccharide (LPS) was used to establish a depression model in rats and PC12 nerve...
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...
ACS Chemical Neuroscience
August 21, 2019
Amelia D Dunn, Brian Reed, Jose Erazo et al.
Biased ligands preferentially activate certain signaling pathways downstream of their target receptor, leading to differential physiological or behavioral responses downstream. The kappa opioid receptor (KOR) is a drug target for diseases involving mood and reward, such as depression and addiction. Biased KOR ligands offer the potential to overcome negative side effects that have previously...
ACS Chemical Neuroscience
March 4, 2019
Lindsay P. Cameron, Charlie J. Benson, Brian C. Defelice et al.
163 citations
-dimethyltryptamine (DMT). The behavioral and cellular effects of this dosing regimen were distinct from those induced following a single high dose of the drug. We found that chronic, intermittent, low doses of DMT produced an antidepressant-like phenotype and enhanced fear extinction learning without impacting working memory or social interaction. Additionally, male rats treated with DMT on...
ACS Chemical Neuroscience
December 27, 2018
Patrick Vizeli, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti
13 citations
Methylenedioxymethamphetamine (MDMA; ecstasy) is used recreationally and has been investigated as an adjunct to psychotherapy. Most acute effects of MDMA can be attributed to activation of the serotonin (5-hydroxytryptamine [5-HT]) system. Genetic variants, such as single-nucleotide polymorphisms (SNPs) and polymorphic regions in 5-HT system genes, may contribute to interindividual differences...
ACS Chemical Neuroscience
September 30, 2018
Julian Maier, Felix P. Mayer, Simon D. Brandt et al.
15 citations
Aminorex (5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) and 4-methylaminorex (4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) are psychostimulants that have long been listed in Schedules IV and I of the UN Convention on Psychotropic Substances of 1971. However, a range of psychoactive analogues exist that are not internationally controlled and therefore often classified as new psychoactive...
ACS Chemical Neuroscience
September 25, 2018
Andrey D. Volgin, Oleg A. Yakovlev, Konstantin A. Demin et al.
38 citations
Hallucinogenic drugs potently alter human behavior and have a millennia-long history of use for medicinal and religious purposes. Interest is rapidly growing in their potential as CNS modulators and therapeutic agents for brain conditions. Antimuscarinic cholinergic drugs, such as atropine and scopolamine, induce characteristic hyperactivity and dream-like hallucinations and form a separate...
ACS Chemical Neuroscience
September 14, 2018
Michael Wasko, Paula A. Witt‐enderby, Christopher K. Surratt
63 citations
The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga's psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was...
ACS Chemical Neuroscience
July 23, 2018
Lindsay P. Cameron, David E. Olson
114 citations
Though relatively obscure, N, N-dimethyltryptamine (DMT) is an important molecule in psychopharmacology as it is the archetype for all indole-containing serotonergic psychedelics. Its structure can be found embedded within those of better-known molecules such as lysergic acid diethylamide (LSD) and psilocybin. Unlike the latter two compounds, DMT is ubiquitous, being produced by a wide variety...
ACS Chemical Neuroscience
July 12, 2018
Lee E. Dunlap, Anne M. Andrews, David E. Olson
105 citations
Better known as "ecstasy", 3,4-methylenedioxymethamphetamine (MDMA) is a small molecule that has played a prominent role in defining the ethos of today's teenagers and young adults, much like lysergic acid diethylamide (LSD) did in the 1960s. Though MDMA possesses structural similarities to compounds like amphetamine and mescaline, it produces subjective effects that are unlike any of the...
ACS Chemical Neuroscience
June 29, 2018
Haden A. Geiger, Madeline G. Wurst, R. Nathan Daniels
139 citations
Psilocybin is found in a family of mushrooms commonly known as "magic mushrooms" that have been used throughout history to induce hallucinations. In the late 1950s Albert Hofmann, of Sandoz Laboratories, identified and synthesized the psychoactive compounds psilocybin and psilocin which are found in psilocybe mushrooms. Psilocybin was marketed by Sandoz as Indocybin for basic...
ACS Chemical Neuroscience
June 4, 2018
Marc Aixalà, Rafael G. Dos Santos, Jaime E. C. Hallak et al.
14 citations
In the past decade, an increasing number of clinical trials are reporting evidence that psychedelics or serotonergic hallucinogens (such as lysergic acid diethylamide, psilocybin, and ayahuasca/dimethyltryptamine) could be effective in the treatment of mood, anxiety, and substance use disorders. The mechanisms responsible for these effects are not fully understood but seem to involve changes in...
ACS Chemical Neuroscience
May 30, 2018
Bruce K. Cassels, Patricio Sáez-briones
84 citations
Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote ( Lophophora williamsii) and the South American wachuma ( Trichocereus pachanoi, T. peruvianus, and T. bridgesii)....
ACS Chemical Neuroscience
April 17, 2018
Lindsay P. Cameron, Charlie J. Benson, Lee E. Dunlap et al.
168 citations
Depression and anxiety disorders are debilitating diseases resulting in substantial economic costs to society. Traditional antidepressants often take weeks to months to positively affect mood and are ineffective for about 30% of the population. Alternatives, such as ketamine, a dissociative anesthetic capable of producing hallucinations, and the psychoactive tisane ayahuasca, have shown great...
ACS Chemical Neuroscience
February 20, 2018
David E. Nichols
87 citations
Lysergic acid diethylamide (LSD) is one of the most potent psychoactive agents known, producing dramatic alterations of consciousness after submilligram (≥20 μg) oral doses. Following the accidental discovery of its potent psychoactive effects in 1943, it was supplied by Sandoz Laboratories as an experimental drug that might be useful as an adjunct for psychotherapy, or to give psychiatrists...