Mystical States achieved through Psychedelics: The Origins, Classical, and Contemporary Use of Psychedelics
Andrew C. Papanicolaou in A Scientific Assessment of the Validity of Mystical Experiences, 2021
On the basis of their chemical structure, the classic psychedelics are divided into two classes. The one includes drugs with a chemical structure like that of tryptamine. Among the drugs in this class are the synthesized psychedelic LSD, psilocybin, and dimethyltryptamine or DMT, which is found in ayahuasca, a psychotropic concoction used ritually in South America. The second category includes substances with a chemical structure similar to phenethylamine. Mescaline, the main psychoactive agent in the peyote (Lophophora williamsii), and other cacti, is the best-known psychedelic of that class. This class includes also several synthesized compounds. The cactus Peyote has been used for millennia by several Mexican Indian tribes including the Chichimeca, Huichol, and Tarahumara tribes, for therapeutic and religious purposes9 and it continues to be used today as a sacrament by the Native American Church to be recounted below.
Hormones of the Moss Protonema
R. N. Chopra, Satish C. Bhatla in Bryophyte Development: Physiology and Biochemistry, 2019
In contrast to the hypothesis of Cove and Ashton,2 experiments with “auxin-resistant” mutants of F. hygrometrica (NAR) indicate another way to reduce the endogenous auxin content. The Funaria mutants were selected in the same way as the Physcomitrella mutants, on a substrate with a high concentration of NAA (5 to 50 μM). The most clearly defined mutant, NAR-2, behaves as a type 4 mutant of P. patens; NAR-4 and -5 resemble the type 5 to 7 mutants.2 The development of NAR-2 can be normalized by a supplement of about 0.1 to 1 μM IAA, α-NAA, or 2,4-D. The precursors indicated in Figure 5 induce the formation of caulonemata, which have the ability to form buds after kinetin treatment (Table 2). Only tryptamine has no significant effect, similar to observations in the wild-type under LLI conditions.38 Therefore, a block in the biosynthetic pathway between tryptophan and IAA could not have caused the auxin deficiency. A reduced sensitivity in the mutants can be excluded by the experiments because the effective concentrations are the same for the mutant NAR-2 and the wild-type in LLI. These are the reasons for assuming that the auxin requirement is due to an enhanced degradation of auxin in the protonema as was demonstrated recently by Atzorn et al.121 using an auxin ELISA test.
Interaction of Drugs of Dependence With Receptors
S.J. Mulé, Henry Brill in Chemical and Biological Aspects of Drug Dependence, 2019
Using physicochemical methods, it has been shown that slight modifications of the psychotomimetic tryptamine derivatives produce ring systems which are similar to LSD, bufotenin, or psilocybin.66–68,93,94 In particular, attempts have been made by Kang and Green68 to relate potency of these drugs to their electronic configuration using molecular orbital calculations. Although it is true that at times such correlations “ are extremely good, this might simply be coincidence. This is inevitable when a series of drugs is examined in animal experiments in which chemical modification can give rise to variable effects on activity, and these effects are modified by such factors as distribution, excretion, metabolism, binding to serum proteins, binding to nonreceptor macromolecules, and ability to penetrate into the CNS. Furthermore, in such complex systems, there is no direct evidence that the drugs are all acting by a common mechanism; this is even true when one is dealing with series of drugs acting on an isolated tissue.95 Such SAR studies carried out in whole animals may have only limited value in defining the configuration of the receptor site which is involved with their effects. A useful test for the ideas which emerged from these various SAR studies would be the antibodies to LSA prepared by Van Vunakis et al.86 Moreover, it was shown that various tryptamine derivatives have graded affinities for this antibody.
A comprehensive study on the relieving effect of Lilium brownii on the intestinal flora and metabolic disorder in p-chlorphenylalanine induced insomnia rats
Published in Pharmaceutical Biology, 2022
Yanpo Si, Wenjun Wei, Xiaohui Chen, Xiaolong Xie, Tao Guo, Yohei Sasaki, Youbo Zhang, Lili Wang, Fei Zhang, Shuying Feng
Compared with the PCPA group, 33 and 66 metabolites were upregulated and downregulated in the LB group, respectively (Figure 7(D)). Among these differential metabolites, a total of 37 metabolites returned to a healthy level after LB intervention (Table 1). The KEGG pathway analysis of metabolites in the LB group showed that the tryptophan metabolic pathway, as well as arachidonic acid metabolic pathway highly associated with insomnia, were mainly adjusted (Figure 8(B)). Insomnia is known to cause disorders in tryptophan metabolism (Bhat et al. 2020). It can be seen from the results of differential metabolites that the tryptamine in the PCPA group was significantly reduced, while the N-γ-acetyl-N-2-formyl-5-methoxykynurenamine (AFMK), as the enzymatic degradation production of 5-HT, was elevated. To our knowledge, tryptamine, as a tryptophan catabolite produced by the gut microbiota, is a β-arylamine neurotransmitter, which is generated by l-tryptophan through the action of pyridoxal phosphate (PLP)-dependent decarboxylases (Williams et al. 2014). Tryptamine, structurally related to serotonin, can be a precursor of the neurotransmitter 5-HT and likely binds to the same site(s) (Mousseau and Butterworth 1994).
Trends in the Top-Cited Articles on Classic Psychedelics
Published in Journal of Psychoactive Drugs, 2021
David Wyndham Lawrence, Bhanu Sharma, Roland R. Griffiths, Robin Carhart-Harris
Psychedelics are a broad class of psychoactive agents defined as substances that induce alterations in perception, mood, cognition, sense of self, and consciousness (Carhart-Harris et al. 2016a, 2016b; Griffiths et al. 2016, 2006; Muttoni, Ardissino, and John 2019; Nichols 2004). Psychedelics can be classified by their “(1) pharmacodynamics and molecular structure; (2) the subjective perceptual, psychological, and/or spiritual effect; and (3) the derived source material” (Lawrence and Carhart-Harris 2019). Classic psychedelics, also described as serotonergic psychedelics, are serotonin 5-HT2A receptor agonists and are structurally related to either tryptamine or phenethylamine (Johnson et al. 2019). Examples of classic psychedelics include psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT), and mescaline (Hendricks et al. 2015; Nichols 2016). Classic psychedelics have shown to be of benefit in the management of major depressive disorder, anxiety, cancer-related existential crisis, and substance use disorders, particularly as an adjuvant to psychotherapy (Carhart-Harris et al. 2018, 2016a; Griffiths et al. 2016, 2006; Johnson et al. 2019; Muttoni, Ardissino, and John 2019; Ross et al. 2016; Uthaug et al. 2019).
Studies of xenobiotic-induced gut microbiota dysbiosis: from correlation to mechanisms
Published in Gut Microbes, 2021
Liang Chi, Pengcheng Tu, Hongyu Ru, Kun Lu
Gut microbiota also can metabolize tryptophan to different neurotransmitters, such as tryptamine and serotonin.144,145 Tryptamine is a product of tryptophan catabolism functioning as a β-arylamine neurotransmitter. Clostridium sporogenes-produced tryptamine by decarboxylating tryptophan induces ion secretion in intestinal epithelial cells which could affect gastrointestinal motility.145 Likewise, another study demonstrated that tryptamine could activate GPCR serotonin receptor-4 to promote fluid secretion and accelerate gut transit.146 Serotonin is another key neurotransmitter in the gut-brain-axis.144 A previous study demonstrated that indigenous spore-forming bacteria in gut microbiota promoted serotonin biosynthesis in colonic enterochromaffin cells, which increased the gastrointestinal motility and enhanced platelet activation and aggregation.147 The gut microbiota-regulated peripheral serotonin synthesis plays a mediatory role in host glucose homeostasis.148 However, how microbiota-derived serotonin affecting neuron system is still largely unclear.
Related Knowledge Centers
- Bufotenin
- Indolamines
- Indole
- Melatonin
- Neuromodulation
- Psilocin
- Psilocybin
- Tryptophan
- Serotonin
- N,N-Dimethyltryptamine