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DMT

Conformational, spectroscopic and nonlinear optical properties of biologically active N,N-dimethyltryptamine molecule: A theoretical study

Abstract

The effective psychoactive properties of N,N-dimethyltryptamine (DMT) known as the near-death molecule have encouraged the imagination of many research disciplines for several decades. Although there is no theoretical study, a number of paper composed by experimental techniques have been reported for DMT molecule. In this study, the molecular modeling of DMT was carried out using B3LYP and HSEh1PBE levels of density functional theory (DFT). Our calculations showed that the energy gap between HOMO and LUMO is low, demonstrating that DMT is a biologically active molecule. Large hyperconjugation interaction energies imply that molecular charge transfer occurs in DMT. Moreover, NLO analysis indicates that DMT can be used an effective NLO material.

Öner, N., Tamer, Ö., Avcı, D., & Atalay, Y. (2014). Conformational, spectroscopic and nonlinear optical properties of biologically active N, N-dimethyltryptamine molecule: A theoretical study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 133, 542-549. https://dx.doi.org/10.1016/j.saa.2014.06.037

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Immunological Effects of Ayahuasca in Humans

Abstract

Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.

dos Santos, R. G. (2014). Immunological Effects of Ayahuasca in Humans. Journal of psychoactive drugs, 46(5), 383-388. https://dx.doi.org/10.1080/02791072.2014.960113

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On the transmethylation hypothesis: stress, N,N-dimethyltryptamine, and positive symptoms of psychosis

Abstract

Past research suggests a relationship between stress and positive symptoms of psychosis. However, the biological substrate of this relationship remains unknown. According to the transmethylation hypothesis, schizophrenia could result from a biochemical disruption in the stress mechanism. This biochemical disruption would lead to the production of a substance that would account for the symptoms of psychosis. Moreover, some studies have tested endogenous N,N-dimethyltryptamine (DMT) in the context of the transmethylation hypothesis. Stress has been found to elevate DMT levels in rodents. Also, elevated DMT levels have been associated with positive features of psychosis in psychiatric patients. Additionally, healthy participants treated with exogenous DMT experience predominantly positive symptoms of psychosis. The present paper examines endogenous DMT as a possible biological mediator of the relationship between stress and positive symptoms of psychosis.

Grammenos, D., & Barker, S. A. (2014). On the transmethylation hypothesis: stress, N, N-dimethyltryptamine, and positive symptoms of psychosis. Journal of Neural Transmission, 1-7. https://dx.doi.org/10.1007/s00702-014-1329-5
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Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells

Abstract

The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.

Szabo, A., Kovacs, A., Frecska, E., & Rajnavolgyi, E. (2014). Psychedelic N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. PloS one, 9(8). https://dx.doi.org/10.1371/journal.pone.0106533
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Potential applications for sigma receptor ligands in cancer diagnosis and therapy

Abstract

Sigma receptors (sigma-1 and sigma-2) represent two independent classes of proteins. Their endogenous ligands may include the hallucinogen N,N-dimethyltryptamine (DMT) and sphingolipid-derived amines which interact with sigma-1 receptors, besides steroid hormones (e.g., progesterone) which bind to both sigma receptor subpopulations. The sigma-1 receptor is a ligand-regulated molecular chaperone with various ion channels and G-protein-coupled membrane receptors as clients. The sigma-2 receptor was identified as the progesterone receptor membrane component 1 (PGRMC1). Although sigma receptors are over-expressed in tumors and up-regulated in rapidly dividing normal tissue, their ligands induce significant cell death only in tumor tissue. Sigma ligands may therefore be used to selectively eradicate tumors. Multiple mechanisms appear to underlie cell killing after administration of sigma ligands, and the signaling pathways are dependent both on the type of ligand and the type of tumor cell. Recent evidence suggests that the sigma-2 receptor is a potential tumor and serum biomarker for human lung cancer and an important target for inhibiting tumor invasion and cancer progression. Current radiochemical efforts are focused on the development of subtype-selective radioligands for positron emission tomography (PET) imaging. Right now, the mostpromising tracers are [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][18F]fluspidine and [18F]FTC-146 for sigma-1 receptors and [11C]RHM-1 and [18F]ISO-1 for the sigma-2 subtype. Nanoparticles coupled to sigma ligands have shown considerable potential for targeted delivery of antitumor drugs in animal models of cancer, but clinical studies exploring this strategy in cancer patients have not yet been reported.

van Waarde, A., Rybczynska, A. A., Ramakrishnan, N. K., Ishiwata, K., Elsinga, P. H., & Dierckx, R. A. (2014). Potential applications for sigma receptor ligands in cancer diagnosis and therapy. Biochimica et Biophysica Acta (BBA)-Biomembranes. https://dx.doi.org/10.1016/j.bbamem.2014.08.022

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Here and now: Discovering the sacred with entheogens

Abstract

Renewed research with entheogens (psychedelic substances) has been able to facilitate the occurrence of mystical forms of consciousness in healthy volunteers with a high degree of reliability. This article explores the potential significance of this development for religious scholars, especially those interested in the study of mysticism. The definition of “mystical consciousness” employed in this research is presented and differentiated from visionary/archetypal and other types of alternative mental states. The ways in which entheogens may be employed with skill and maximum safety are discussed. Implications for clarifying confusion in the study of mysticism are considered, along with suggestions for future religious research on this frontier of knowledge.

Richards, W.  A. (2014). Here and now: Discovering the sacred with entheogens. Zygon: Journal of Religion and Science, 49(3), 652-665. http://dx.doi.org/10.1111/zygo.12108
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Does the Nervous System Have an Intrinsic Archaic Language? Entoptic Images and Phosphenes

Abstract

Psychoactive plants have been consumed by many cultures, cults and groups during religious rituals and ceremonies for centuries and they have been influential on the eruption of the many images, secret and religious symbols, esoteric geometrical shapes, archetypes, religious figures, philosophy of religions since the dawn of Homo sapiens. Some of the psychoactive plants used for religious purposes were; narcotic analgesics (opium), THC (cannabis), psilocybin (magic mushrooms), mescaline (peyote), ibogaine (Tabernanthe iboga), DMT (Ayahuasca and phalaris species), peganum harmala, bufotenin, muscimol (Amanita muscaria), Thujone (Absinthe, Arthemisia absinthium), ephedra, mandragora, star lotus, salvia divinorum etc. An important property of these natural chemicals is to induce the human psyche to perceive some optical forms and shapes, which are existent in the subconscious and collective unconsciousness, and which emerge during some certain trance states and ASCs. Some of these simple geometric forms are called entoptic images and phosphenes. Entopic images and phosphenes have been found in various cultural art work and the drawings of cave walls, which were formed during the shamanic religious rituals since the Neolithic times. Also entoptic images exist in many folkloric, traditional and cultures geometrical shapes. Long before the creation of languages, visual perception and information was the only source for the mankind to perceive outer world, as it is the only one in the primate world. This article reviews the possibility of an ancient forgotten visual sign and symbol language, which is genetically existent in the human brain and that, emerges out during ASCs, trance states and the consciousness altered by the psychoactive plants. The basics of this geometrical sign and symbol language may have generated the formation of some archetypal symbols and concepts, which are yet to be discovered. Near to this, emerging of many attributes of the sub-or-un-consciousness, during those “psychedelic plant journeys” had had a prodigious impact on the formation and creation of many religious “figures, characters, creatures, archetype images” that today exist, not only in the mythology, but also in many religions, as well, such as angels, spirits, Jinns, demons, Satan, mythological creatures, supra-natural creatures, gods, and goddesses. Mystical and religious experiences during the rituals using psychoactive plants may have also helped the archaic ancestral information, coded in the limbic system, to come out onto the consciousness, which may also have helped the evolution of the hominoids and Homo sapiens.

Sayin, H. U. (2014). Does the Nervous System Have an Intrinsic Archaic Language? Entoptic Images and Phosphenes. Neuroquantology, 12(3), 427-445. https://dx.doi.org/10.14704/nq.2014.12.3.756
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Recent advances in the neuropsychopharmacology of serotonergic hallucinogens

Abstract

Serotonergic hallucinogens, such as (+)-lysergic acid diethylamide, psilocybin, and mescaline, are somewhat enigmatic substances. Although these drugs are derived from multiple chemical families, they all produce remarkably similar effects in animals and humans, and they show cross-tolerance. This article reviews the evidence demonstrating the serotonin 5-HT2A receptor is the primary site of hallucinogen action. The 5-HT2A receptor is responsible for mediating the effects of hallucinogens in human subjects, as well as in animal behavioral paradigms such as drug discrimination, head twitch response, prepulse inhibition of startle, exploratory behavior, and interval timing. Many recent clinical trials have yielded important new findings regarding the psychopharmacology of these substances. Furthermore, the use of modern imaging and electrophysiological techniques is beginning to help unravel how hallucinogens work in the brain. Evidence is also emerging that hallucinogens may possess therapeutic efficacy.

Halberstadt, A. L. (2014). Recent advances in the neuropsychopharmacology of serotonergic hallucinogens. Behavioural Brain Research, 277, 99-120. http://dx.doi.org/10.1016/j.bbr.2014.07.016
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The Consumption of Psychoactive Plants in Ancient Global and Anatolian Cultures During Religious Rituals: The Roots of the Eruption of Mythological Figures and Common Symbols in Religions and Myths

Abstract

Psychoactive plants which contain hallucinogenic molecules that induce a form of altered states of consciousness (H-ASC) have been widely used during the religious rituals of many cultures throughout the centuries, while the consumption of these plants for spiritual and religious purposes is as old as human history. Some of those cultures were shaman and pagan subcultures; African native religions; Bwiti Cult; South American native religions; Amazon Cultures; Central American Cultures; Mexican subcultures; Aztec, Maya and Inca; Wiccan and witch subcultures; Satanists; American Indians; Greek and Hellenistic cultures; Sufis; Hassan Sabbah’s Hashissins; Hindu, Indian and Tibetan cultures; some of the Nordic subcultures etc. Some of the psychoactive ingredients of the plants that were used during these religious rituals were; narcotic analgesics (opium), THC (cannabis), psilocybin (magic mushrooms), mescaline (peyote), ibogaine (Tabernanthe iboga), DMT (Ayahuasca and phalaris species), Peganum harmala, bufotenin, muscimol (Amanita muscaria), thujone (absinthe, Arthemisia absinthium), ephedra, mandragora, star lotus, Salvia divinorum etc. The main purposes of the practice of these plants were: spiritual healing; to contact with spirits; to contact with the souls of ancestors; to reach enlightenment (Nirvana or Satori); to become a master shaman, pagan or witch; to reach so-called-other realities, etc. Such “psychedelic-philosophical plant rituals” changed participating persons’ psychology, philosophy and personality to a great degree. In these two successive articles, the consumption of psychedelic plants during religious rituals is reviewed and it is hypothesized that the images, Figures, illusions and hallucinations experienced during these “plant trips” had a great impact on the formation and creation of many Figures, characters, creatures, archetype images that exist not only in the mythology, but also in many religions, as well, such as angels, demons, Satan, mythological creatures, gods, goddesses etc. In the Middle East and Anatolia, within many hermetic and pagan religions, Greek and Hellenic cultures psychoactive plant use was a serious part of the religious rituals, such as Dionysian rituals or Witch’s’ Sabbaths. Although the impact of the “psychedelic experience and imagination” was enormous to the configuration of many religious and mythological characters, and archetypes, this fact has been underestimated and even unnoticed by many historians and anthropologists, because of the quasi-ethical trends of “anti-drug-brain-washed Western Societies”.
Sayin, H. U. (2014). The Consumption of Psychoactive Plants in Ancient Global and Anatolian Cultures During Religious Rituals: The Roots of the Eruption of Mythological Figures and Common Symbols in Religions and Myths. NeuroQuantology, 12(2), 276-296. https://dx.doi.org/10.14704/nq.2014.12.2.753
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Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes

Abstract

Rationale
Synthetic hallucinogenic tryptamines, especially those originally described by Alexander Shulgin, continue to be abused in the USA. 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.

Blough, B. E., Landavazo, A., Decker, A. M., Partilla, J. S., Baumann, M. H., & Rothman, R. B. (2014). Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology, 231(21), 4135-4144. http://dx.doi.org/10.1007/s00213-014-3557-7
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