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DMT

Neuropharmacology of N,N-Dimethyltryptamine

April 25, 2016 / DMT, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

N,N-Dimethyltryptamine (DMT) is an indole alkaloid widely found in plants and animals. It is best known for producing brief and intense psychedelic effects when ingested. Increasing evidence suggests that endogenous DMT plays important roles for a number of processes in the periphery and central nervous system, and may act as a neurotransmitter. This paper reviews the current literature of both the recreational use of DMT and its potential roles as an endogenous neurotransmitter. Pharmacokinetics, mechanisms of action in the periphery and central nervous system, clinical uses and adverse effects are also reviewed. DMT appears to have limited neurotoxicity and other adverse effects except for intense cardiovascular effects when administered intravenously in large doses. Because of its role in nervous system signaling, DMT may be a useful experimental tool in exploring how brain works, and may also be a useful clinical tool for treatment of anxiety and psychosis.

Carbonaro, T. M., & Gatch, M. B. (2016). Neuropharmacology of N, N-Dimethyltryptamine. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.04.016

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Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class

November 17, 2015 / DMT, Neuroscience, Papers, Publications / By / , , , ,

Abstract

New psychoactive substances (NPS) are not tested for their cytochrome P450 (CYP) inhibition potential before consumption. Therefore, this potential was explored for tryptamine-derived NPS (TDNPS) including alpha-methyl tryptamines (AMTs), dimethyl tryptamines (DMTs), diallyl tryptamines (DALTs), and diisopropyl tryptamines (DiPTs) using test substrates preferred by the Food and Drug Administration in a cocktail assay. All tested TDNPS with the exception of DMT inhibited CYP2D6 activity with IC50 values below 100 μM. DALTs inhibited CYP2D6 activity similar to paroxetine and quinidine and CYP1A2 activity comparable to fluvoxamine. 5-Methoxy-N,N-diallyltryptamine reduced in vivo the caffeine metabolism in rats consistent with in vitro results. Five of the AMTs also inhibited CYP1A2 activity comparable to amiodarone. AMT and 6-F-AMT inhibited CYP2A6 activity in the range of the test inhibitor tranylcypromine. CYP2B6 activity was inhibited by 19 tryptamines, but weakly compared to efavirenz. CYP2C8 activity was inhibited by five of the tested TDNPS and three showed values comparable to trimethoprim and gemfibrozil. Six tryptamines inhibited CYP2C9 and seven CYP2C19 activities comparable to fluconazole and chloramphenicol, respectively. Nineteen compounds showed inhibition of CYP2E1 and 18 of CYP3A activity, respectively. These results showed that the CYP inhibition by TDNPS might be clinically relevant, but clinical studies are needed to explore this further.

Dinger, J., Woods, C., Brandt, S. D., Meyer, M. R., & Maurer, H. H. (2015). Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicology Letters. http://dx.doi.org/10.1016/j.toxlet.2015.11.013
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Plant and Fungal Hallucinogens as Toxic and Therapeutic Agents

November 9, 2015 / Biology & Ethnobotany, DMT, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Psychology, Publications, Salvia / Salvinorin A / By / ,

Abstract

This chapter aimed to provide an overview of the large number of hallucinogens of natural origin. Following a literature review, the following hallucinogens were selected for a detailed description that considered their essential chemical groups: indoleamines (N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, bufotenine, psilocybin, and ibogaine), phenylethylamines (mescaline), tropane alkaloids (atropine and scopolamine), cannabinoids (Δ9-tetrahydrocannabinol), and a neoclerodane diterpenoid (salvinorin A). The following species were included as representative of each drug class: Mimosa tenuiflora, Psychotria viridis, Banisteriopsis caapi, Virola spp., Psilocybe spp., Tabernanthe iboga, Tabernaemontana spp., Lophophora spp., Trichocereus spp., Atropa belladonna, Brugmansia spp., Cannabis sativa, and Salvia divinorum, among others. In addition to psychopharmacological effects, this chapter aims to address the sociocultural and historical use of these hallucinogenic plants and mushrooms, along with the importance of both the set and the setting factors that affect the profound consciousness-altering effects of these compounds. Moreover, the use of animal models to predict the hallucinogenic properties of psychoactive plants and compounds and to investigate the mechanisms of action of psychodysleptic drugs is discussed. This chapter also attempts to establish a parallel between hallucinogens and endogenous neurotransmitters in humans, to compare the pharmacological and psychic action of these compounds, to evaluate hallucinogens’ ability to produce symptoms typical of certain mental disorders during their use, and to investigate the role of these compounds as therapeutic agents in several psychopathological conditions.

Carlini, E. A., & Maia, L. O. (2015). Plant and Fungal Hallucinogens as Toxic and Therapeutic Agents.

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Acute Biphasic Effects of Ayahuasca

September 30, 2015 / Ayahuasca, DMT, Neuroscience, Papers, Psychology, Publications / By / , , , , ,

Abstract

Ritual use of ayahuasca, an amazonian Amerindian medicine turned sacrament in syncretic religions in Brazil, is rapidly growing around the world. Because of this internationalization, a comprehensive understanding of the pharmacological mechanisms of action of the brew and the neural correlates of the modified states of consciousness it induces is important. Employing a combination of electroencephalogram (EEG) recordings and quantification of ayahuasca’s compounds and their metabolites in the systemic circulation we found ayahuasca to induce a biphasic effect in the brain. This effect was composed of reduced power in the alpha band (8–13 Hz) after 50 minutes from ingestion of the brew and increased slow- and fast-gamma power (30–50 and 50–100 Hz, respectively) between 75 and 125 minutes. Alpha power reductions were mostly located at left parieto-occipital cortex, slow-gamma power increase was observed at left centro-parieto-occipital, left fronto-temporal and right frontal cortices while fast-gamma increases were significant at left centro-parieto-occipital, left fronto-temporal, right frontal and right parieto-occipital cortices. These effects were significantly associated with circulating levels of ayahuasca’s chemical compounds, mostly N,N-dimethyltryptamine (DMT), harmine, harmaline and tetrahydroharmine and some of their metabolites. An interpretation based on a cognitive and emotional framework relevant to the ritual use of ayahuasca, as well as it’s potential therapeutic effects is offered.

Schenberg E.E., Alexandre J.F.M., Filev R., Cravo A.M., Sato J.R., Muthukumaraswamy S.D., et al. (2015) Acute Biphasic Effects of Ayahuasca. PLoS ONE 10(9): e0137202. http://dx.doi.org/10.1371/journal.pone.0137202
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Psychedelic medicine: a re-emerging therapeutic paradigm

September 8, 2015 / Ayahuasca, DMT, Humanities & Art, LSD, MDMA, Mushrooms / Psilocybin, Papers, Publications / By / ,

Introduction

In clinical research settings around the world, renewed investigations are taking place on the use of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder (PTSD). Since the termination of a period of research from the 1950s to the early 1970s, most psychedelic substances have been classified as “drugs of abuse” with no recognized medical value. However, controlled clinical studies have recently been conducted to assess the basic psychopharmacological properties and therapeutic efficacy of these drugs as adjuncts to existing psychotherapeutic approaches. Central to this revival is the re-emergence of a paradigm that acknowledges the importance of set (i.e., psychological expectations), setting (i.e., physical environment) and the therapeutic clinician–patient relationship as critical elements for facilitating healing experiences and realizing positive outcomes [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”][…]
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Yensen, R., & Johnson, M. W. (2015). Psychedelic medicine: a re-emerging therapeutic paradigm. https://dx.doi.org/10.1503/cmaj.141124
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Psychedelic medicine: A re-emerging therapeutic paradigm

December 6, 2021 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, DMT, Ketamine, LSD, MDMA, Mescaline / Cacti, Papers, Psychology, Publications / By / , , ,

Introduction

In clinical research settings around the world, renewed investigations are taking place on the use of psychedelic substances for treating illnesses such as addiction, depression, anxiety and posttraumatic stress disorder (PTSD). Since the termination of a period of research from the 1950s to the early 1970s, most psychedelic substances have been classified as “drugs of abuse” with no recognized medical value. However, controlled clinical studies have recently been conducted to assess the basic psychopharmacological properties and therapeutic efficacy of these drugs as adjuncts to existing psychotherapeutic approaches. Central to this revival is the re-emergence of a paradigm that acknowledges the importance of set (i.e., psychological expectations), setting (i.e., physical environment) and the therapeutic clinician–patient relationship as critical elements for facilitating healing experiences and realizing positive outcomes [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”][…]

Tupper, K. W., Wood, E., Yensen, R., & Johnson, M. W. (2015). Psychedelic medicine: a re-emerging therapeutic paradigm. CMAJ: Canadian Medical Association journal= journal de l’Association medicale canadienne, 187(14), 1054. https://dx.doi.org/10.1503/cmaj.141124
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Psychedelics and Immunomodulation: Novel Approaches and Therapeutic Opportunities

July 14, 2015 / DMT, LSD, MDMA, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications / By /

Abstract

Classical psychedelics are psychoactive substances, which, besides their psychopharmacological activity, have also been shown to exert significant modulatory effects on immune responses by altering signaling pathways involved in inflammation, cellular proliferation, and cell survival via activating NF-κB and mitogen-activated protein kinases. Recently, several neurotransmitter receptors involved in the pharmacology of psychedelics, such as serotonin and sigma-1 receptors, have also been shown to play crucial roles in numerous immunological processes. This emerging field also offers promising treatment modalities in the therapy of various diseases including autoimmune and chronic inflammatory conditions, infections, and cancer. However, the scarcity of available review literature renders the topic unclear and obscure, mostly posing psychedelics as illicit drugs of abuse and not as physiologically relevant molecules or as possible agents of future pharmacotherapies. In this paper, the immunomodulatory potential of classical serotonergic psychedelics, including N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-iodoamphetamine, and 3,4-methylenedioxy-methamphetamine will be discussed from a perspective of molecular immunology and pharmacology. Special attention will be given to the functional interaction of serotonin and sigma-1 receptors and their cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signaling. Furthermore, novel approaches will be suggested feasible for the treatment of diseases with chronic inflammatory etiology and pathology, such as atherosclerosis, rheumatoid arthritis, multiple sclerosis, schizophrenia, depression, and Alzheimer’s disease.

Szabo, A. Psychedelics and immunomodulation: Novel approaches and therapeutic opportunities. Frontiers in Immunology, 0. https://dx.doi.org/10.3389/fimmu.2015.00358
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Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.

June 3, 2015 / Ayahuasca, DMT, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1 mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated.

Pic-Taylor, A., da Motta, L. G., de Morais, J. A., Junior, W. M., Santos, A. D. F. A., Campos, L. A., … & Caldas, E. D. (2015). Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat. Behavioural processes. http://dx.doi.org/10.1016/j.beproc.2015.05.004
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A Note on the Docking of some Hallucinogens to the 5-HT2A Receptor

April 20, 2015 / DMT, Mescaline / Cacti, Papers, Pharmacology & Chemistry, Publications / By / ,

Abstract

The activation of 5-HT2A receptors by the binding of some ligands produces several altered states of consciousness in humans. The knowledge of the manner a hallucinogen interacts with this receptor should be the first step to know how these chemicals transfer information to produce the final biological effect(s). Here, we present the results of a docking study of some hallucinogens (LSD, mescaline, DMT, 25I-NBOMe and others), to a recent model of the 5-HT2A receptor. The rigid and flexible residues approach es were employed. The best approach is to allow conformational flexibility to the residues of the binding site. The Val-156 residue appears to be common to all flexible docking results and all molecules interact with the transmembrane 3 helix. The other interactions are particular to each molecule.

Gómez-Jeria, J. S., & Robles-Navarro, A. (2015). A Note on the Docking of some Hallucinogens to the 5-HT2A Receptor. Journal of Computational Methods in Molecular Design, 5(1), 45-57.
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