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Ayahuasca dimethyltryptamine, and psychosis: a systematic review of human studies

February 23, 2017 / Ayahuasca, DMT, Papers, Psychology, Publications / By / , ,

Abstract

Ayahuasca is a hallucinogen brew traditionally used for ritual and therapeutic purposes in Northwestern Amazon. It is rich in the tryptamine hallucinogens dimethyltryptamine (DMT), which acts as a serotonin 5-HT2A agonist. This mechanism of action is similar to other compounds such as lysergic acid diethylamide (LSD) and psilocybin. The controlled use of LSD and psilocybin in experimental settings is associated with a low incidence of psychotic episodes, and population studies corroborate these findings. Both the controlled use of DMT in experimental settings and the use of ayahuasca in experimental and ritual settings are not usually associated with psychotic episodes, but little is known regarding ayahuasca or DMT use outside these controlled contexts. Thus, we performed a systematic review of the published case reports describing psychotic episodes associated with ayahuasca and DMT intake. We found three case series and two case reports describing psychotic episodes associated with ayahuasca intake, and three case reports describing psychotic episodes associated with DMT. Several reports describe subjects with a personal and possibly a family history of psychosis (including schizophrenia, schizophreniform disorders, psychotic mania, psychotic depression), nonpsychotic mania, or concomitant use of other drugs. However, some cases also described psychotic episodes in subjects without these previous characteristics. Overall, the incidence of such episodes appears to be rare in both the ritual and the recreational/noncontrolled settings. Performance of a psychiatric screening before administration of these drugs, and other hallucinogens, in controlled settings seems to significantly reduce the possibility of adverse reactions with psychotic symptomatology. Individuals with a personal or family history of any psychotic illness or nonpsychotic mania should avoid hallucinogen intake.

dos Santos, R. G., Bouso, J. C., & Hallak, J. E. (2017). Ayahuasca dimethyltryptamine, and psychosis: a systematic review of human studies. Therapeutic Advances in Psychopharmacology, 2045125316689030. 10.1177/2045125316689030
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Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N,N-dimethyltryptamine

February 13, 2017 / Ayahuasca, DMT, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

Dimethyltryptamines are hallucinogenic serotonin-like molecules present in traditional Amerindian medicine (e.g. Ayahuasca, Virola) recently associated with cognitive gains, antidepressant effects and changes in brain areas related to attention, self-referential thought, and internal mentation. Historical and technical restrictions impaired understanding how such substances impact human brain metabolism. Here we used shotgun mass spectrometry to explore proteomic differences induced by dimethyltryptamine (5-methoxy-N,N-dimethyltryptamine, 5-MeO-DMT) on human cerebral organoids. Out of the 6,728 identified proteins, 934 were found differentially expressed in 5-MeO-DMT-treated cerebral organoids. In silico systems biology analyses support 5-MeO-DMT’s anti-inflammatory effects and reveal a modulation of proteins associated with the formation of dendritic spines, including proteins involved in cellular protrusion formation, microtubule dynamics and cytoskeletal reorganization. Proteins involved in long-term potentiation were modulated in a complex manner, with significant increases in the levels of NMDAR, CaMKII and CREB, but a reduction of PKA and PKC levels. These results offer possible mechanistic insights into the neuropsychological changes caused by the ingestion of substances rich in dimethyltryptamines.

Dakic, V., Nascimento, J. M., Sartore, R. C., de Moraes Maciel, R., de Araujo, D. B., Ribeiro, S., … & Rehen, S. K. (2017). Short term changes in the proteome of human cerebral organoids induced by 5-methoxy-N, N-dimethyltryptamine. bioRxiv, 108159.
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Serotonergic Hallucinogen-Induced Visual Perceptual Alterations

November 30, 2016 / DMT, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD), psilocybin, and N,N-dimethyltryptamine (DMT), are famous for their capacity to temporally and profoundly alter an individual’s visual experiences. These visual alterations show consistent attributes despite large inter- and intra-individual variances. Many reports document a common perception of colors as more saturated, with increased brightness and contrast in the environment (“Visual Intensifications”). Environmental objects might be altered in size (“Visual illusions”) or take on a modified and special meaning for the subject (“Altered self-reference”). Subjects may perceive light flashes or geometrical figures containing recurrent patterns (“Elementary imagery and hallucinations”) influenced by auditory stimuli (“Audiovisual synesthesia”), or they may envision images of people, animals, or landscapes (“Complex imagery and hallucinations”) without any physical stimuli supporting their percepts. This wide assortment of visual phenomena suggests that one single neuropsychopharmacological mechanism is unlikely to explain such vast phenomenological diversity. Starting with mechanisms that act at the cellular level, the key role of 5-HT2A receptor activation and the subsequent increased cortical excitation will be considered. Next, it will be shown that area specific anatomical and dynamical features link increased excitation to the specific visual contents of hallucinations. The decrease of alpha oscillations by hallucinogens will then be introduced as a systemic mechanism for amplifying internal-driven excitation that overwhelms stimulus-induced excitations. Finally, the hallucinogen-induced parallel decrease of the N170 visual evoked potential and increased medial P1 potential will be discussed as key mechanisms for inducing a dysbalance between global integration and early visual gain that may explain several hallucinogen-induced visual experiences, including visual hallucinations, illusions, and intensifications.

Kometer, M., & Vollenweider, F. X. (2016). Serotonergic Hallucinogen-Induced Visual Perceptual Alterations. 10.1007/7854_2016_461
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Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging

October 31, 2016 / Ayahuasca, DMT, LSD, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Publications / By / , , ,

Abstract

Serotonergic hallucinogens produce alterations of perceptions, mood, and cognition, and have anxiolytic, antidepressant, and antiaddictive properties. These drugs act as agonists of frontocortical 5-HT2A receptors, but the neural basis of their effects are not well understood. Thus, we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man. Studies published in the PubMed, Lilacs, and SciELO databases until 12 April 2016 were included using the following keywords: “ayahuasca”, “DMT”, “psilocybin”, “LSD”, “mescaline” crossed one by one with the terms “mri”, “fmri”, “pet”, “spect”, “imaging” and “neuroimaging”. Of 279 studies identified, 25 were included. Acute effects included excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, and inhibition of the default mode network. Long-term use was associated with thinning of the posterior cingulate cortex, thickening of the anterior cingulate cortex, and decreased neocortical 5-HT2A receptor binding. Despite the high methodological heterogeneity and the small sample sizes, the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & Hallak, J. E. (2016). Classical hallucinogens and neuroimaging: A systematic review of human studies: Hallucinogens and neuroimaging. Neuroscience & Biobehavioral Reviews, 71, 715-728. 10.1016/j.neubiorev.2016.10.026
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Classic Psychedelics and Rational Suicide in the Elderly: Exploring the Potential Utility of a Reemerging Treatment Paradigm

October 29, 2016 / Ayahuasca, DMT, LSD, Mescaline / Cacti, Papers, Psychology, Publications / By / ,

Abstract

The objective of the current chapter is to evaluate the potential utility of classic psychedelics including dimethyltryptamine (found in the Amazonian plant decoction ayahuasca), lysergic acid diethylamide (LSD), mescaline (found in peyote and other psychoactive cacti), and psilocybin (found in certain mushrooms) in addressing rational suicide among the elderly. An overview of the sociopolitical history of classic psychedelics is presented, followed by an examination of empirical findings pertaining to rational suicide. This chapter concludes that classic psychedelics may counteract rational suicide among the elderly by promoting the perception that life is worth living even in the face of great adversity and encourages future study on this important topic.

Hendricks, P. S., & Grob, C. S. (2017). Classic Psychedelics and Rational Suicide in the Elderly: Exploring the Potential Utility of a Reemerging Treatment Paradigm. In Rational Suicide in the Elderly (pp. 203-210). Springer International Publishing. 10.1007/978-3-319-32672-6_14

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Psychedelic Psychotherapy Insights From 25 Years of Research

September 29, 2016 / DMT, LSD, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

Presented at a conference titled “Psychedelic Science 2013,” highlighting the resumption of investigations with psychedelic substances (i.e., psilocybin, DMT, LSD, MDMA, etc.) in the United States and Europe after a dormant period of more than two decades, the author presents insights and perspectives gleaned from his 25 years of clinical research experience. After acknowledging the vastness and potential significance of this research frontier, the article focuses on the “cartography of inner space”; the unique therapeutic potential of transcendental states of consciousness; the entelechy of the interpersonally grounded psyche; the importance of integration in drug-free therapy sessions; the roles of expectation, religious education and faith; the role of music; and future research directions.

Richards, W. A. (2016). Psychedelic Psychotherapy Insights From 25 Years of Research. Journal of Humanistic Psychology, 0022167816670996. 10.1177/0022167816670996
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The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells

September 14, 2016 / DMT, Neuroscience, Papers, Publications / By / , , , , ,

Abstract

N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper, we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells, iPSCs), monocyte-derived macrophages (moMACs), and dendritic cells (moDCs). Results showed that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.

Szabo, A., Kovacs, A., Riba, J., Djurovic, S., Rajnavolgyi, E., & Frecska, E. (2016). The Endogenous Hallucinogen and Trace Amine N, N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells. Frontiers in Neuroscience, 10, 423. http://dx.doi.org/10.3389/fnins.2016.00423
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Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens

July 29, 2016 / Ayahuasca, DMT, Papers, Psychology, Publications / By / , , ,

Abstract

Objective: In the present study we explored the psychometric properties of three widely used questionnaires to assess the subjective effects of hallucinogens: the Hallucinogen Rating Scale (HRS), the Mystical Experience Questionnaire (MEQ), and the Addiction Research Center Inventory (ARCI).

Methods: These three questionnaires were administered to a sample of 158 subjects (100 men) after taking ayahuasca, a hallucinogen whose main active component is N,N-dimethyltryptamine (DMT). A confirmatory factorial study was conducted to check the adjustment of previous data obtained via theoretical proposals. When this was not possible, we used an exploratory factor analysis without restrictions, based on tetrachoric and polychoric matrices and correlations.

Results: Our results sparsely match the theoretical proposals of the authors, perhaps because previous studies have not always employed psychometric methods appropriate to the data obtained. However, these data should be considered preliminary, pending larger samples to confirm or reject the proposed structures obtained.

Conclusions: It is crucial that instruments of sufficiently precise measurement are utilized to make sense of the information obtained in the study of the subjective effects of psychedelic drugs.

Bouso, J. C., Pedrero‐Pérez, E. J., Gandy, S., & Alcázar‐Córcoles, M. Á. (2016). Measuring the subjective: revisiting the psychometric properties of three rating scales that assess the acute effects of hallucinogens. Human Psychopharmacology: Clinical and Experimental, 31(5), 356-372. 10.1002/hup.2545
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A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

June 30, 2016 / DMT, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel “alternate universe,” often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient “beings.” The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 minutes—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modelling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anaesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

Gallimore, A. R. and Strassman, R. (2016). A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience. Frontiers in Pharmacology. http://dx.doi.org/10.3389/fphar.2016.00211
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DMT: Beyond the trip, a potential multifaceted medicine

December 6, 2021 / DMT, Publications / By

DMT-emergencyN,N-dimethyltryptamine, more commonly known as DMT, is an exceptionally fast-acting and powerful psychedelic. DMT can be ingested by drinking the entheogenic brew ayahuasca, injected intravenously, intramuscularly or through inhalation. It is produced endogenously in a variety of plants and animals, including in humans. DMT exerts physiological effects that go beyond its mind-altering effects, as discussed in Jacob and Presti (2005). For example, DMT has been shown to induce anxiolytic and antidepressant effects (Sanches et al. 2016).

DMT is not only an agonist of serotonin 2A and 2C receptors (5-HT2A and 5-HT2C); it also binds to σ1 putative receptors and trace amine receptors (Vitale et al. 2011). In addition, its serotonergic analogues can influence immunoregulation, and may even prevent carcinogenesis (Frecska et al. 2012). DMT’s multifaceted interactions show that its effects are not limited to the central nervous system but may play a more crucial role in the body’s cellular protective mechanisms (Frecska et al. 2012).

Dr. Ede Frecska has published multiple papers on the effects of ayahuasca and DMT on creativity, tissue regeneration, and the interhemispheric fusion in altered states of consciousness (Frecska et al. 2016). With the recent discovery of DMT’s activation of the σ1 receptor , which plays a crucial role in protecting the body from undergoing oxidative stress, Dr. Frecska and his team are currently investigating DMT’s role in neuroprotection prior to clinical death (Frecska 2015).

σ1 receptors play a key role in neuroprotection by regulating both neuronal development and morphogenesis. This is done through the regulation and manipulation of oxidative stress and mitochondrial functions (Tuerxun et al. 2010). Agonists of σ1 receptors exacerbate neuroprotective effects by inhibiting intracellular calcium overload and by thwarting the activation of pro-apoptopic genes, as well as activating protective genes, as shown in stroke models (Zhang et al. 2012). This leads to the reduction of calcium neurotoxicity, prevents oxidative stress-induced cell death, and can stimulate neuronal plasticity (Kourrich et al. 2012). Most importantly, the constant activation of σ1 receptors during ischemia leads to a reduction of neurotoxicity (Katnik et al. 2006). Ultimately, this research suggests that DMT may have a role in reducing the hypoxic-anoxic damages such as local anoxia (e.g. stroke) or general hypoxia (e.g. cardiac arrest) (Kourrich et al. 2012).

DMT’s medicinal properties are not limited to neuroprotection, but can extend to immunoprotection as well. The 5HT2A receptors, as well as the sigma receptors, can profoundly influence the body’s immune system. Serotonin plays an important role in cellular immune functions, and more specifically in the elimination of pathogens and cancer cells (O’Connell et al. 2006). σ1 receptor agonists can increase the production of anti-inflammatory cytokines as well as reduce pro-inflammatory cytokines. Both these processes are important in reducing the cellular damage in case of injury or disease (Frecska et al. 2012).

Currently, there is only speculation that DMT is produced during near-death experiences, as there are few parallels between near-death experiences and DMT visions (Strassman 2001). However, based on limited information, one may conjecture the production of DMT during life-threatening situations. McEwen and Sober (1967) have demonstrated that when undergoing extreme environmental stress, rabbits produce vast quantities of DMT in the lungs, which are then released into the blood (McEwen & Sober 1967). DMT is then transported through the neural membranes within synaptic vesicles and delivered to the brain. Knowing the relationship between DMT and the σ1 receptors, it is hypothesised that DMT limits or reverses the accumulated oxidative stress. This serves as the foundation of Dr. Frecska’s hypothesis, and if evidence is found of DMT’s role in the neuroprotection of the human brain in the stages leading up to clinical death, then DMT would have the potential to be used as an emergency medicine. If successful, one could envision the use of DMT ampoules to be used intravenously in ambulances, operating rooms and in disaster zones. Clinical studies with humans are still necessary in order to define whether it is feasible or not.

Although Dr. Frescka’s studies focus on rats (pre-clinical studies), his studies have looked beyond DMT’s mere hallucinogenic relevance and have opened avenues into further studying DMT’s neuroprotective role. The potential medical ramifications are vast. The applications of DMT may be beyond what we can imagine, and certainly deserve to be systematically studied.

References

Frecska, E., 2015. What role does the ‘spirit molecule’ DMT play in the brain?. [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”][Online] Available at: http://walacea.com/campaigns/dmt

Frecska, E., Bokor, P. & Winkelman, M., 2016. The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization. Frontiers in Pharmacology, p. 10.3389.

Frecska, E. et al., 2012. A possibly sigma-1 receptor meditated dole of dimethyltryptamine in tissue protection, regeneration and immunity. Translational Neuroscience, pp. 1-18.

Jacob, M. & Presti, D., 2005. Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.. Medical Hypotheses, 64(5), pp. 930-7.

Katnik, C. et al., 2006. Sigma-1 receptor activation prevents intracellular calcium dysregulation in cortical neurons during in vitro ischemia. Journal of Pharmacology and Experimental Therapeutics, Band 319, pp. 1355-1365.

Kourrich, S., Tsung-Ping, S., Fujimoto, M. & Bonci, A., 2012. The sigma-1 receptor: roles in neuronal plasticity and disease. Trends Neuroscience, 35(12), pp. 762-771.

McEwen, C. & Sober, A., 1967. Rabbit serum monoamine oxidase. The Journal of Biological Chemistry, Band 242, pp. 3068-3078.

O’Connell, P. et al., 2006. A novel form of immune signaling revealed by transmission of the inflammatory mediator serotnin between dendritic cells and T cells. Blood, Band 107, pp. 1010-1017.

Sanches, R. F. et al., 2016. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study. Journal of Clinical Psychopharmacology, 36(1), pp. 77-81.

Strassman, R., 2001. DMT: The Spirit Molecule. First Hrsg. Rochester: Park Street Press.

Strassman, R. & Qualis, C., 1994. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects. Archives of General Psychiatry, pp. 85-97.

Tuerxun, T. et al., 2010. SA4503, a sigma-1 receptor agonist, prevents cultured cortical neurons from oxidative stress-induced cell death via suppression of MAPK pathway activation and glutamate receptor expression. Neuroscience Letters, Band 469, pp. 303-308.

Zhang, Y. et al., 2012. Sigma-1 receptor agonists provide neuroprotection against gp12- via a change in bel-2 expression in mouse neuronal cultures. Brain Research, Band 1431, pp. 13-22.

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