scholarly journals 5-methoxy-N,N-dimethyltryptamine: An ego-dissolving endogenous neurochemical catalyst of creativity

2019 ◽  
Author(s):  
Christopher B. Germann

Abstract5-Methoxy-N,N-dimethyltryptamine (acronymized as 5-MeO-DMT) is sui generis among the numerous naturally-occurring psychoactive substances due to its unparalleled ego-dissolving effects which can culminate in a state of nondual consciousness (which is phenomenologically similar to transformative peak experiences described in various ancient contemplative traditions, e.g., Advaita Vedānta, Mahāyāna Buddhism). The enigmatic molecule is endogenous to the human brain and has profound psychological effects which are hitherto only very poorly understood due to the absence of scientifically controlled human experimental trials. Its exact neuronal receptor binding profile is a matter of ongoing scientific research, however, its remarkable psychoactivity is presumably mediated via agonism of the 5-HT2A (serotonin) receptor subtype. Anthropological/ethnopharmacological evidence indicates that various cultures utilized 5-MeO-DMT containing plants for medicinal, psychological, and spiritual purposes for millennia. In this paper we argue that this naturally occurring serotonergic compound could be fruitfully utilized as a neurochemical research tool which has the potential to significantly advance our understanding of the cognitive and neuronal processes which underpin cognition and creativity (downregulation of the default-mode network, increased neuronal functional connectivity, etc.). An eclectic interdisciplinary perspective is adopted, and we present converging evidence from a plurality of sources in support of this conjecture. Specifically, we suggest that 5-MeO-DMT has great potential in this respect due to its incommensurable capacity to completely disintegrate self-referential cognitive/neuronal processes (viz., “ego death”). The importance of unbiased systematic scientific research on naturally occurring endogenous psychoactive compounds is discussed from a Jamesian radical empiricism perspective and potential scenarios of abuse are discussed (particularly in the context of military torture).

2005 ◽  
Vol 18 (2) ◽  
pp. 113
Author(s):  
Myung Ha Yoon ◽  
Hong Buem Bae ◽  
Jeong Il Choi ◽  
Seok Jae Kim ◽  
Chang Mo Kim ◽  
...  

2021 ◽  
Vol 22 (10) ◽  
pp. 5285
Author(s):  
Kazuhiro Mio ◽  
Shoko Fujimura ◽  
Masaki Ishihara ◽  
Masahiro Kuramochi ◽  
Hiroshi Sekiguchi ◽  
...  

Serotonin receptors play important roles in neuronal excitation, emotion, platelet aggregation, and vasoconstriction. The serotonin receptor subtype 2A (5-HT2AR) is a Gq-coupled GPCR, which activate phospholipase C. Although the structures and functions of 5-HT2ARs have been well studied, little has been known about their real-time dynamics. In this study, we analyzed the intramolecular motion of the 5-HT2AR in living cells using the diffracted X-ray tracking (DXT) technique. The DXT is a very precise single-molecular analytical technique, which tracks diffraction spots from the gold nanocrystals labeled on the protein surface. Trajectory analysis provides insight into protein dynamics. The 5-HT2ARs were transiently expressed in HEK 293 cells, and the gold nanocrystals were attached to the N-terminal introduced FLAG-tag via anti-FLAG antibodies. The motions were recorded with a frame rate of 100 μs per frame. A lifetime filtering technique demonstrated that the unliganded receptors contain high mobility population with clockwise twisting. This rotation was, however, abolished by either a full agonist α-methylserotonin or an inverse agonist ketanserin. Mutation analysis revealed that the “ionic lock” between the DRY motif in the third transmembrane segment and a negatively charged residue of the sixth transmembrane segment is essential for the torsional motion at the N-terminus of the receptor.


2001 ◽  
Vol 281 (3) ◽  
pp. G798-G808 ◽  
Author(s):  
H. Takahara ◽  
M. Fujimura ◽  
S. Taniguchi ◽  
N. Hayashi ◽  
T. Nakamura ◽  
...  

Few previous studies have discussed the changes in serotonin receptor activity in the small intestine of diabetic animals. Therefore, we examined serotonin content in duodenal tissue and dose-dependent effects of serotonin agonists and antagonists on the motor activity of ex vivo vascularly perfused duodenum of streptozotocin (STZ)-diabetic rats. Serotonin content was significantly increased in enterochromaffin cells but not altered in serotonin-containing neurons in STZ-diabetic rats. Motor activity assessed by frequency, amplitude, and percent motility index per 10 min of pressure waves was reduced in the duodenum of diabetic rats, and this reduction was reversed by insulin treatment. Serotonin dose dependently increased the motor activity in control rat duodenum but only a higher concentration of serotonin increased the motor activity in diabetic rats. The 5-hydroxytryptamine (5-HT) receptor subtype 4 (5-HT4) antagonist SB-204070 dose dependently reduced motor activity in both control and diabetic rats, whereas the 5-HT3receptor antagonist azasetron, even at a higher concentration, failed to affect motor activity in diabetic rat duodenum but dose dependently reduced motor activity in control rat duodenum. These results suggest that 5-HT3receptor activity was impaired but 5-HT4receptor activity was intact in STZ-diabetic rat duodenum. Such an impairment of 5-HT3receptor activity may induce the motility disturbance in the small intestine of diabetes mellitus.


Author(s):  
Sabine Niebert ◽  
Gijsbert J. van Belle ◽  
Steffen Vogelgesang ◽  
Till Manzke ◽  
Marcus Niebert

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5186 ◽  
Author(s):  
Serena Silvestro ◽  
Giovanni Schepici ◽  
Placido Bramanti ◽  
Emanuela Mazzon

Cannabidiol (CBD) is a non-psychoactive phytocannabinoid known for its beneficial effects including antioxidant and anti-inflammatory properties. Moreover, CBD is a compound with antidepressant, anxiolytic, anticonvulsant and antipsychotic effects. Thanks to all these properties, the interest of the scientific community for it has grown. Indeed, CBD is a great candidate for the management of neurological diseases. The purpose of our review is to summarize the in vitro and in vivo studies published in the last 15 years that describe the biochemical and molecular mechanisms underlying the effects of CBD and its therapeutic application in neurological diseases. CBD exerts its neuroprotective effects through three G protein coupled-receptors (adenosine receptor subtype 2A, serotonin receptor subtype 1A and G protein-coupled receptor 55), one ligand-gated ion channel (transient receptor potential vanilloid channel-1) and one nuclear factor (peroxisome proliferator-activated receptor γ). Moreover, the therapeutical properties of CBD are also due to GABAergic modulation. In conclusion, CBD, through multi-target mechanisms, represents a valid therapeutic tool for the management of epilepsy, Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.


2000 ◽  
Vol 6 (4) ◽  
pp. 270-277 ◽  
Author(s):  
André Ludovic Phanjoo

The sexual behaviour of older people is more often the target of jocularity or ridicule than the subject of serious scientific research. As a consequence, relatively little is known about the sexual behaviour of the over-65s and such information as is available shows a polarisation according to gender, male sexual behaviour and dysfunction being viewed very much in the light of physical problems, whereas women's sexual behaviour revolves around attitudes towards sexuality and the psychological effects of ageing. This review will address the biological changes associated with ageing, the psychological and social concomitants, the prevalence of sexual dysfunction, its aetiological factors, and the management of common sexual problems including those found in an institutional setting.


2011 ◽  
Vol 31 (2) ◽  
pp. 114
Author(s):  
T.W. Goecke ◽  
A.B. Ekici ◽  
B. Niesler ◽  
C.R. Loehberg ◽  
C. Hammer ◽  
...  

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