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Traumländer



dabei seit 2015
94 Forenbeiträge

  Geschrieben: 07.12.17 19:56
Long-term use of psychedelic drugs is associated with differences in brainstructure and personality in humans

Busco et al. schrieb:
Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown.
Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue.

Wenn es genial ist, ist es typisch.
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dabei seit 2012
3.258 Forenbeiträge
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5 Galerie-Bilder

  Geschrieben: 25.01.18 12:05
Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug

Izyaslav Lapin schrieb:
Phenibut (β-phenyl-γ-aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA-mimetic, primarily at GABAB and, to some extent, at GABAA receptors. It also stimulates dopamine receptors and antagonizes β-phenethylamine (PEA), a putative endogenous anxiogenic. The psychopharmacological activity of phenibut is similar to that of baclofen, a p-Cl-derivative of phenibut. This article reviews the structure-activity relationship of phenibut and its derivatives. Emphasis is placed on the importance of the position of the phenyl ring, the role of the carboxyl group, and the activity of optical isomers. Comparison of phenibut with piracetam and diazepam reveals similarities and differences in their pharmacological and clinical effects. Phenibut is widely used in Russia to relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic patients; as well as a pre- or post-operative medication. It is also used in the therapy of disorders characterized by asthenia and depression, as well as in post-traumatic stress, stuttering and vestibular disorders.

I take drugs like life’s my Friday
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dabei seit 2012
3.258 Forenbeiträge
1 Tripberichte
5 Galerie-Bilder

  Geschrieben: 04.02.18 14:27
Erowid Datenbank für Paper:

https://www.erowid.org/references/
I take drugs like life’s my Friday
Traumländer



dabei seit 2015
704 Forenbeiträge
5 Tripberichte
1 Galerie-Bilder

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  Geschrieben: 06.02.18 22:00
Nasal mucosal versus gastrointestinal absorption of nasally administered cocaine
Sie umschlingen einander in der Hoffnung, zusammenzuwachsen und so ihre Einheit wiedergewinnen zu können.
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dabei seit 2012
3.258 Forenbeiträge
1 Tripberichte
5 Galerie-Bilder

  Geschrieben: 17.02.18 23:19
Das Journal Psychopharmacology hat seine neuste Ausgabe der psychedelischen Forschung gewidmet. Hier mal die Open-Access-Artikel der Ausgabe:

Psychedelics and related drugs: therapeutic possibilities, mechanisms and regulation

Long-lasting subjective effects of LSD in normal subjects

Direct comparison of the acute subjective, emotional, autonomic, and endocrine effects of MDMA, methylphenidate, and modafinil in healthy subjects

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression

Psilocybin with psychological support for treatment-resistant depression: six-month follow-up

The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research

Insbesondere das letzte Paper weckt mein Interesse, kommen doch die Wissenschaftler zu einem beruhigenden Schluss:

Henningfield et al. schrieb:
Kratom leaves and extracts have been used for centuries in Southeast Asia and elsewhere to manage pain and other disorders and, by mid-twentieth century, to manage opioid withdrawal. Kratom has some opioid effects but low respiratory depression and abuse potential compared to opioids of abuse. This appears due to its non-opioid-derived and resembling molecular structure recently referred to as biased agonists. By the early 2000s, kratom was increasingly used in the US as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain and opioid withdrawal by people seeking abstinence from opioids. There has been no documented threat to public health that would appear to warrant emergency scheduling of the products and placement in Schedule I of the CSA carries risks of creating serious public health problems.

I take drugs like life’s my Friday
Traumländer



dabei seit 2012
1.740 Forenbeiträge
4 Tripberichte

  Geschrieben: 21.02.18 20:59
Verteilung der THC-Gehalte in Marihuanapflanzen
Bestimmung der Gehalte in Wurzeln, Stängeln, Blättern und Blüten



Guten Schlaf suchte man sich und mohnblumige Tugenden dazu!
Allen diesen gelobten Weisen der Lehrstühle war Weisheit der Schlaf ohne Träume: sie kannten keinen bessern Sinn des Lebens.
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dabei seit 2012
3.258 Forenbeiträge
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5 Galerie-Bilder

  Geschrieben: 03.03.18 20:24
Decarboxylation of Tetrahydrocannabinolic acid (THCA) to active THC
I take drugs like life’s my Friday
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dabei seit 2010
2.125 Forenbeiträge
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3 Langzeit-TB
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  Geschrieben: 13.03.18 17:46
Acute Pharmacological Effects of 2C-B in Humans: An Observational Study ; frontiersin.org
"The only way to write honestly about the scene is to be part of it. If there is one quick truism about psychedelic drugs, it is that anyone who tries to write about them without first-expierience is a fool and a fraud." ― Hunter S. Thompson (1967)
Traumländer

dabei seit 2013
200 Forenbeiträge
1 Langzeit-TB
5 Galerie-Bilder

Homepage
  Geschrieben: 13.03.18 23:41
Pupillenverhalten unter akutem Thc Einfluss “ist teilweise verzögert, teilweise beschleunigt, teilweise praktisch unverändert”

zu alt für den Scheiß
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dabei seit 2012
3.258 Forenbeiträge
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5 Galerie-Bilder

  Geschrieben: 24.03.18 22:02
Taming THC potential cannabis synergy and phytocannabinoid‐terpenoid entourage effects

Ethan Russo schrieb:
Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolatedand synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesiahave been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol andcannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabischemotypes expressing high titres of each component for future study. This review will explore another echelon ofphytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, a-pinene, linalool, b-caryophyllene, caryophylleneoxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrancecomponents common to human diets that have been designated Generally Recognized as Safe by the US Food and DrugAdministration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviourwhen inhaled from ambient air at serum levels in the single digits ng·mL-1. They display unique therapeutic effects that maycontribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed onphytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation,depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcusaureus). Scientific evidence is presented for non-cannabinoid plant components as putative antidotes to intoxicating effects ofTHC that could increase its therapeutic index. Methods for investigating entourage effects in future experiments will beproposed. Phytocannabinoid-terpenoid synergy, if proven, increases the likelihood that an extensive pipeline of newtherapeutic products is possible from this venerable plant.

I take drugs like life’s my Friday
Traumländer



dabei seit 2014
100 Forenbeiträge
1 Galerie-Bilder

  Geschrieben: 05.04.18 20:47
zuletzt geändert: 05.04.18 20:59 durch Dao (insgesamt 1 mal geändert)

»Zu einer Erkenntnis […] muß man durch Not, Leiden an seiner Fülle gekommen sein, muß geglaubt haben, ›entwurzelt‹ zu sein […], muß am Intellekt gelitten und ihn durch den Geist überwunden – muß mit dem Menschen gerungen haben.«
— Ernst Toller
Moderator



dabei seit 2012
3.258 Forenbeiträge
1 Tripberichte
5 Galerie-Bilder

  Geschrieben: 15.04.18 20:22
Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes

Blough et al. schrieb:
Abstract
  • Rationale — Synthetic hallucinogenic tryptamines, especially those originally described by
    Alexander Shulgin, continue to be abused in the United States. The range of subjective
    experiences produced by different tryptamines suggests that multiple neurochemical mechanisms
    are involved in their actions, in addition to the established role of agonist activity at serotonin-2A
    (5-HT2A) receptors.

  • Objectives — This study evaluated the interaction of a series of synthetic tryptamines with
    biogenic amine neurotransmitter transporters and with serotonin (5-HT) receptor subtypes
    implicated in psychedelic effects.

  • Methods — Neurotransmitter transporter activity was determined in rat brain synaptosomes.
    Receptor activity was determined using calcium mobilization and DiscoveRx PathHunter® assays
    in HEK293, Gα16-CHO, and CHOk1 cells transfected with human receptors.
    Results—Twenty-one tryptamines were analyzed in transporter uptake and release assays, and 5-
    HT2A, serotonin 1A (5-HT1A), and 5-HT2A β-arrestin functional assays. Eight of the compounds
    were found to have 5-HT-releasing activity. Thirteen compounds were found to be 5-HT uptake
    inhibitors or were inactive. All tryptamines were 5-HT2A agonists with a range of potencies and
    efficacies, but only a few compounds were 5-HT1A agonists. Most tryptamines recruited β-arrestin
    through 5-HT2A activation.

  • Conclusions — All psychoactive tryptamines are 5-HT2A agonists, but 5-HT transporter (SERT)
    activity may contribute significantly to the pharmacology of certain compounds. The in vitro
    transporter data confirm structure-activity trends for releasers and uptake inhibitors whereby
    releasers tend to be structurally smaller compounds. Interestingly, two tertiary amines were found
    to be selective substrates at SERT, which dispels the notion that 5-HT-releasing activity is limited
    only to primary or secondary amines

I take drugs like life’s my Friday
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dabei seit 2012
3.258 Forenbeiträge
1 Tripberichte
5 Galerie-Bilder

  Geschrieben: 17.04.18 12:30
zuletzt geändert: 17.04.18 14:33 durch Neopunk (insgesamt 2 mal geändert)
Soo, heute gibts ein paar aufschlussreiche Paper zum Thema 5-HT2A-Rezeptor, dem Serotoninrezeptorsubtyp, an welchem assoziative Psychedelika wirken.

Molecular Basis of Partial Agonism: Orientation of Indoleamine Ligands in the Binding Pocket of the Human Serotonin 5-HT2A Receptor Determines Relative Efficacy

Ebersole et al. schrieb:
Abstract:

Based on experiment and computational simulation, we present a structural explanation for the differing efficacies of indole agonists at the human serotonin 5-HT2A receptor (5HT2AR). We find that serotonin [5-hydroxytryptamine (5-HT)] forms hydrogen-bonds with Ser3.36 in helix 3 and Ser5.46 in helix 5. Disruption of these hydrogen bonds by methyl-substitution of the cationic primary amine or of the backbone N1-amine, respectively, leads to a reduction in agonist efficacy. Computational simulation predicts that mutation of Ser3.36 to Ala should allow a similar interaction with helix 3 both for agonists that have unmodified cationic amine side chains and for those with substituted amines. Experimentally, this mutation was found to largely eliminate the differences in efficacy caused by cationic amine substitution for a series of indole congeners. Similarly, substitution of the N1-amine, which interacts with Ser5.46, reduced efficacy more markedly at the wild-type (WT) than at the Ser5.46Ala mutant receptor. Computational modeling of binding pocket interactions of ligands with WT and mutant receptor constructs demonstrate how the Ser3.36 and Ser5.46 interactions serve to modify the agonist's favored position in the binding pocket. A striking correlation was found between differences in the position assumed by the indole ring and differences in agonist activity. These data support the hypothesis that the position of the agonist interacting with the receptor is influenced by specific interactions in helices 3 and 5 and determines the degree of receptor activation by agonist through a mechanism that is likely to be shared by other G-protein coupled receptors in this class.


High‐Affinity Agonist Binding Correlates with Efficacy (Intrinsic Activity) at the Human Serotonin 5‐HT2A and 5‐HT2C Receptors: Evidence Favoring the Ternary Complex and Two‐State Models of Agonist Action

Fitzgerald et al. schrieb:
Abstract:

Many modern models of receptor‐G protein function assume that there is a direct relationship between high‐affinity agonist binding and efficacy. The validity of this assumption has been recently questioned for the serotonin 5‐HT2A receptor. We examined the intrinsic activities of various ligands in activating phosphoinositide hydrolysis and measured their respective binding affinities to the high‐ and low‐affinity states of the 5‐HT2C (VNV isoform) and 5‐HT2A receptors. Ligand binding affinities for the high‐affinity state of the receptors were determined using 1‐(4‐[125I]iodo‐2,5‐dimethoxyphenyl)‐2‐aminopropane, whereas [3H]mesulergine and N‐[3H]methylspiperone were used, in the presence of excess guanine nucleotide [guanosine 5′‐O‐(3‐thiotriphosphate)], to define binding to the low‐affinity state of the 5‐HT2C and 5‐HT2A receptors, respectively. Antagonists labeled the high‐ and low‐affinity states of each receptor with comparable affinities. Previously identified inverse agonists of the 5‐HT2C receptor behaved as silent antagonists in our systems even when the receptor was over‐expressed at a relatively high density. In contrast, the ability of agonists to bind differentially to the high‐ and low‐affinity states of the 5‐HT2A and 5‐HT2C receptors was highly correlated (r2= 0.86 and 0.96, respectively) with their intrinsic activities. These data suggest that high‐affinity agonist states can account for agonist efficacy at human 5‐HT2A or 5‐HT2C receptors without the need for considering additional transition or active states of the receptor‐ligand complex. The procedure described herein may expedite drug
discovery efforts by predicting intrinsic activities of ligands solely from ligand binding assays.


Related Contribution of Specific Helix 2 and 7 Residues to Conformational Activation of the Serotonin 5-HT2A Receptor

Sealfon et al. schrieb:
Abstract:

A conserved helix 2 Asp is required for the proper function of many G-protein-coupled receptors. To reveal the structural basis for the role of this residue, the additive effects of mutations at this locus and at a conserved helix 7 locus were investigated in the 5-HT2A receptor. All mutant receptors studied retained high affinity agonist and antagonist binding. Whereas an Asp → Asn mutation in helix 2 eliminated coupling, interchanging the residues at the two positions by a second mutation of Asn → Asp in helix 7 restored receptor function. These data suggest that these residues are adjacent in space and interact. The loss of function observed with Ala at either position is consistent with each side chain forming hydrogen bonds. Molecular dynamics simulations were performed on three-dimensional computational models of agonist-receptor complexes of both the wild-type receptor and the Asp → Asn mutant receptor. Consonant with the lack of coupling observed for the mutant construct, introducing the mutation into the computational model produced a conformational change in a direction opposite to that seen from computational simulations of activation of the wild-type receptor model. These results implicate both loci in a common hydrogen-bonding network underlying receptor activation by agonist.


Assessment of the Roles of Serines 5.43(239) and 5.46(242) for Binding and Potency of Agonist Ligands at the Human Serotonin 5-HT2A Receptor


Braden & Nichols schrieb:
Abstract:
We assessed the relative importance of two serine residues located near the top of transmembrane helix 5 of the human 5-HT2A receptor, comparing the wild type with S5.43(239)A or S5.46(242)A mutations. Using the ergoline lysergic acid diethylamide (LSD), and a series of substituted tryptamine and phenethylamine 5-HT2A receptor agonists, we found that Ser5.43(239) is more critical for agonist binding and function than Ser5.46(242). Ser5.43(239) seems to engage oxygen substituents at either the 4- or 5-position of tryptamine ligands and the 5-position of phenylalkylamine ligands. Even when a direct binding interaction cannot occur, our data suggest that Ser5.43(239) is still important for receptor activation. Polar ring-substituted tryptamine ligands also seem to engage Ser5.46(242), but tryptamines lacking such a substituent may adopt an alternate binding orientation that does not engage this residue. Our results are consistent with the role of Ser5.43(239) as a hydrogen bond donor, whereas Ser5.46(242) seems to serve as a hydrogen bond acceptor. These results are consistent with the functional topography and utility of our in silico-activated homology model of the h5-HT2A receptor. In addition, being more distal from the absolutely conserved Pro5.50, a strong interaction with Ser5.43(239) may be more effective in straightening the kink in helix 5, a feature that is possibly common to all type A GPCRs that have polar residues at position 5.43.


Molecular Interaction of Serotonin 5-HT2A Receptor Residues Phe339(6.51) and Phe340(6.52) with Superpotent N-Benzyl Phenethylamine Agonists

Braden et al. (David Nichols als Coauthor) schrieb:
Abstract:

Experiments were conducted to examine the molecular basis for the high affinity and potency of a new class of 5-HT2A receptor agonists, N-benzyl phenethylamines. Competition binding assays at several serotonin receptors confirmed that an N-arylmethyl substitution was necessary for affinity increases up to 300-fold over simple N-alkyl homologs, as well as enhanced selectivity for 5-HT2A versus 5-HT2C and 5-HT1A receptors. PI hydrolysis functional assays confirmed that these N-benzyl phenethylamines are potent and highly efficacious agonists at the rat 5-HT2A receptor. Virtual docking of these compounds into a human 5-HT2A receptor homology model indicated that the N-benzyl moiety might be interacting with Phe339(6.51), whereas the phenethylamine portion was likely to be interacting with Phe340(6.52). Experiments in h5-HT2A receptors with Phe339(6.51)L and Phe340(6.52)L mutations seem to support this hypothesis. Dramatic detrimental effects on affinity, potency, and intrinsic activity were observed with the Phe339(6.51)L mutation for all N-benzyl analogs, whereas most N-unsubstituted phenethylamines and traditional agonists were only weakly affected, if at all. Consistent with other published studies, the Phe340(6.52)L mutation detrimentally affected affinity, potency, and intrinsic activity of nearly all compounds tested, although a strong change in intrinsic activity was not seen with most N-aryl analogs. These data further validate the topology of our h5-HT2A receptor homology model. It is noteworthy that this study is the first to identify a hitherto unrecognized role for residue 6.51 in agonist activation of a serotonin G protein-coupled receptor (GPCR), whereas most previous reports have suggested a varied and sometimes contradictory role in homologous GPCRs.


Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties

Shan et al. schrieb:
Abstract:

From computational simulations of a serotonin 2A receptor (5-HT2AR) model complexed with pharmacologically and structurally diverse ligands we identify different conformational states and dynamics adopted by the receptor bound to the full agonist 5-HT, the partial agonist LSD, and the inverse agonist Ketanserin. The results from the unbiased all-atom molecular dynamics (MD) simulations show that the three ligands affect differently the known GPCR activation elements including the toggle switch at W6.48, the changes in the ionic lock between E6.30 and R3.50 of the DRY motif in TM3, and the dynamics of the NPxxY motif in TM7. The computational results uncover a sequence of steps connecting these experimentally-identified elements of GPCR activation. The differences among the properties of the receptor molecule interacting with the ligands correlate with their distinct pharmacological properties. Combining these results with quantitative analysis of membrane deformation obtained with our new method (Mondal et al, Biophysical Journal 2011), we show that distinct conformational rearrangements produced by the three ligands also elicit different responses in the surrounding membrane. The differential reorganization of the receptor environment is reflected in (i)-the involvement of cholesterol in the activation of the 5-HT2AR, and (ii)-different extents and patterns of membrane deformations. These findings are discussed in the context of their likely functional consequences and a predicted mechanism of ligand-specific GPCR oligomerization.


Head‐twitch response in rodents induced by the hallucinogen 2,5‐dimethoxy‐4‐iodoamphetamine: a comprehensive history, a re‐evaluation of mechanisms, and its utility as a model

Canal & Morgan schrieb:
Abstract:

Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two‐lever drug discrimination procedure and the drug‐induced head‐twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5‐HT2) receptor agonist, 2,5‐dimethoxy‐4‐iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up‐to‐date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two‐lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals.


A Highly Conserved Aspartic Acid (Asp-155) Anchors the Terminal Amine Moiety of Tryptamines and Is Involved in Membrane Targeting of the 5-HT2A Serotonin Receptor But Does Not Participate in Activation via a “Salt-Bridge Disruption” Mechanism

Kristiansen et al. schrieb:
Abstract:

Discovering the molecular and atomic mechanism(s) by which G-protein-coupled receptors (GPCRs) are activated by agonists remains an elusive goal. Recently, studies examining two representative GPCRs (rhodopsin and α1b-adrenergic receptors) have suggested that the disruption of a putative “salt-bridge” between highly conserved residues in transmembrane (TM) helix III, involving aspartate or glutamate, and helix VII, involving a basic residue, results in receptor activation. We have tested whether this is a general mechanism for GPCR activation by constructing a model of the 5-hydroxytryptamine (5-HT)2A receptor and characterizing several mutations at the homologous residues (Asp-155 and Asn-363) of the 5-HT2Aserotonin receptor. All of the mutants (D155A, D155N, D155E, D155Q, and S363A) resulted in receptors with reduced basal activity; in no case was evidence for constitutive activity revealed. Structure-function studies with tryptamine analogs and various Asp-155 mutants demonstrated that Asp-155 interacts with the terminal, and not indole, amine moiety of 5-HT2A agonists. Interestingly, the D155E mutation interfered with the membrane targeting of the 5-HT2A receptor, and an inverse relationship was discovered when comparing receptor activation and targeting for a series of Asp-155 mutants. This represents the first known instance in which a charged residue located in a putative TM helix alters the membrane targeting of a GPCR. Thus, for 5-HT2A receptors, the TMIII aspartic acid (Asp-155) is involved in anchoring the terminal amine moiety of indole agonists and in membrane targeting and not in receptor activation by salt-bridge disruption.



I take drugs like life’s my Friday
Moderator



dabei seit 2010
2.125 Forenbeiträge
14 Tripberichte
3 Langzeit-TB
10 Galerie-Bilder

  Geschrieben: 23.04.18 19:42
“The Words of McKenna”: Healing, Political Critique, and the Evolution of Psychonaut Religion since the 1960s Counterculture

Andrew Monteith schrieb:
Terence McKenna (1946–2000) spent thirty years advocating for the religious use of hallucinogenic substances. Picking up where Timothy Leary left off, McKenna inspired later generations of Psychonauts (“consciousness explorers”) and continues to do so even today. McKennan religion treats humanity as in flux, with imminent evolutionary milestones rapidly approaching. These metamorphoses will occur in conjunction with substance use and the help of other entities. American Psychonaut religion developed alongside the Drug War, which has had far-reaching consequences for its evolution. In establishing an enforced state opposition to substances that Psychonauts consider sacraments, the American legal system catalyzed the development of countercultural religion. Psychonauts following McKenna's philosophy have embraced anarchism and anticapitalism, adhering to an ideology that presents “archaic” society as an ideal set against America's current “dominator” society. Beyond the Psychonauts themselves, the Drug War also appears to have inhibited scholarly inquiry into how substance use can function as a religious practice.



"The only way to write honestly about the scene is to be part of it. If there is one quick truism about psychedelic drugs, it is that anyone who tries to write about them without first-expierience is a fool and a fraud." ― Hunter S. Thompson (1967)

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