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Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents

/ Ayahuasca, Papers, Psychiatry & Medicine, Publications / / , , , , ,

Abstract

A series of N(9)-substituted harmine derivatives were synthesized and evaluated for their anticancer activity on a panel of cancer cell lines, their apoptosis induction and their cell cycle effects. The results showed that N(9)-substituted harmine derivatives had anticancer effects. In particular, N(9)-haloalkyl derivatives 9a-9c and N(9)-acyl harmine derivatives 11c and 11d, with IC50 values less than 1μM, were more potent than doxorubicin against A-549 and/or MCF-7 cell lines. Moreover, structure-activity relationships (SARs) indicated that introducing a haloalkyl or benzenesulfonyl group in the N(9)-position of harmine could significantly increase the anticancer activity. The most active compound (11d) caused cell cycle arrest in the G2/M phase, and induced cell apoptosis in a dose-dependent manner.
Du, H., Tian, S., Chen, J., Gu, H., Li, N., & Wang, J. (2016). Synthesis and biological evaluation of N 9-substituted harmine derivatives as potential anticancer agents. Bioorganic & medicinal chemistry letters, 26(16), 4015-4019. 10.1016/j.bmcl.2016.06.087
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A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

/ DMT, Neuroscience, Papers, Psychology, Publications / / ,

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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Ketamine abuse potential and use disorder

/ Ketamine, Neuroscience, Papers, Publications / / , , ,

Abstract

Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine. However, the therapeutic value of ketamine to treat psychiatric disorders faces a major challenge that ketamine also owns significant reinforcing and toxic effects. Its abuse has posted severe harms on individuals and society. Disrupted learning and memory processing has long been related with ketamine use. It is hypothesized that ketamine blocks NMDA receptors on gamma-aminobutyric acid (GABA) neurons inside the thalamic reticular nucleus, which leads to disinhibition of dopaminergic neurons and increased release of dopamine. Currently, there is no specific treatment for treating every ketamine patient presenting peripheral toxicity. Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs. Future research can continue to develop creative ways to investigate potential mechanism and treatments related to ketamine abuse that have posted severe individual and social harms.

Liu, Y., Lin, D., Wu, B., & Zhou, W. (2016). Ketamine abuse potential and use disorder. Brain research bulletin. http://dx.doi.org/0.1016/j.brainresbull.2016.05.016
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Major Depressive Disorder Induced by Chronic Ketamine Abuse: A Case Report

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications, Substance Use Disorder / / , ,

Abstract

Ketamine, an NMDA (N-methyl-d-aspartate) glutamate antagonist, commonly used as an anesthetic agent, has emerged as a major substance of abuse particularly in Asia.1 Here, we present, to our knowledge, the first case of a patient who developed major depressive episodes after heavy and long-term ketamine use.

Chang, H., Huang, M. C., & Chen, L. Y. (2016). Major Depressive Disorder Induced by Chronic Ketamine Abuse: A Case Report. The Primary Care Companion for CNS Disorders, 18(3). 10.4088%2FPCC.15l01881
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Spirituality, drugs, and tourism: tourists’ and shamans’ experiences of ayahuasca in Iquitos, Peru

/ Anthropology & Sociology, Ayahuasca, Papers, Publications / / , , ,

Abstract

This study critically evaluates the complex inter space of spirituality, drugs, and tourism through tourists’ and shamans’ accounts of ayahuasca tourism in Iquitos, Peru. Ayahuasca is a hallucinogenic beverage traditionally consumed for spiritual and health purposes. Using micro-ethnography, one of the researchers was immersed for one month in the tourism experience of ayahuasca. The findings reveal the ambivalent nature of tourists’ experiences and the changing meaning and practices of ayahuasca. Tourists’ encounters with ayahuasca were perceived as spiritual due to better understanding and perception of ‘self’ and ‘others’. Shamans’ encounters with tourists were mostly positive but negative consequences on their practices were evident. The study highlights issues of fluidity, positionality, and self-identification of roles in tourism.

Prayag, G., Mura, P., Hall, C. M., & Fontaine, J. (2016). Spirituality, drugs, and tourism: tourists’ and shamans’ experiences of ayahuasca in Iquitos, Peru. Tourism Recreation Research, 1-12. 10.1080/02508281.2016.1192237
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Robin Carhart-Harris – Brain imaging and depression research with psychedelics

/ Uncategorized /

Brain imaging and depression research with psychedelics
The talk will review brain imaging work on the action of psychedelics on the brain and describe the results of a clinical trial assessing psilocybin as a treatment for depression. It will also review the broader societal impact of psychedelic drug-use and discuss its implications.
Biography
Robin Carhart-Harris studies the brain effects of LSD, psilocybin (magic mushrooms), and MDMA. Most recently he has completed the first phase of a clinical trial looking at the potential of psilocybin to treat depression.

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Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo’s Nest

/ Papers, Philosophy & Religious Studies, Publications / /

Abstract

This is an attempt to investigate the causal relationship existing between the psychedelic literary genre in fiction and the application of trauma theory in the study of One Flew over the Cuckoo’s Nest. Trauma theory, which is a psychological theory in essence; has been widely linked to the study of literature since traumatic responses take narrative forms. Scientifically, many studies have proven that the psychedelic trip leads to a deepened exploration of the unconscious tracing latent emotional traumas. Henceforth, I am going to explore this novel as a psychedelic example of science fiction through a generic analysis due to the numerous parallels I have noticed with the effects of drug administration on real life patients. I will base my claim on a medical theory known as Psychedelic Information Theory which investigates psychedelic hallucinations, expanded consciousness and their impact on the metaphysical aspects of self-exploration. Consequently, I shall presuppose that psychedelics act metaphorically on the text of One Flew over the Cuckoo’s Nest inducing character-based hallucinatory narratives. Hallucinations are caused by an eruption of a psychedelic consciousness that is the antithesis of the normal state of a mind. Hallucinations range from happy enjoyable experiences laden with kaleidoscopic colourful streams of visions to painful manifestations of latent trauma. I endeavour to analyze this novel as a traumatic example of psychedelic fiction through establishing a cause-result relationship between information theory and trauma theory as a fluid encounter between literature and science within science fiction framework. Finally, I attempt to link the cultural integration of psychedelics to the shift of the traumatic experience from cultural to structural. This paper explores primarily the manifestations of Chief Bromden’s historic trauma. It traces secondarily the psychedelic characteristics of the novel. Lastly, it studies the effects of Bromden’s psychedelic journey on his traumatic recovery.

Besbes, M. (2016). Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo’s Nest.
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Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo's Nest

/ Papers, Philosophy & Religious Studies, Publications / /

Abstract

This is an attempt to investigate the causal relationship existing between the psychedelic literary genre in fiction and the application of trauma theory in the study of One Flew over the Cuckoo’s Nest. Trauma theory, which is a psychological theory in essence; has been widely linked to the study of literature since traumatic responses take narrative forms. Scientifically, many studies have proven that the psychedelic trip leads to a deepened exploration of the unconscious tracing latent emotional traumas. Henceforth, I am going to explore this novel as a psychedelic example of science fiction through a generic analysis due to the numerous parallels I have noticed with the effects of drug administration on real life patients. I will base my claim on a medical theory known as Psychedelic Information Theory which investigates psychedelic hallucinations, expanded consciousness and their impact on the metaphysical aspects of self-exploration. Consequently, I shall presuppose that psychedelics act metaphorically on the text of One Flew over the Cuckoo’s Nest inducing character-based hallucinatory narratives. Hallucinations are caused by an eruption of a psychedelic consciousness that is the antithesis of the normal state of a mind. Hallucinations range from happy enjoyable experiences laden with kaleidoscopic colourful streams of visions to painful manifestations of latent trauma. I endeavour to analyze this novel as a traumatic example of psychedelic fiction through establishing a cause-result relationship between information theory and trauma theory as a fluid encounter between literature and science within science fiction framework. Finally, I attempt to link the cultural integration of psychedelics to the shift of the traumatic experience from cultural to structural. This paper explores primarily the manifestations of Chief Bromden’s historic trauma. It traces secondarily the psychedelic characteristics of the novel. Lastly, it studies the effects of Bromden’s psychedelic journey on his traumatic recovery.

Besbes, M. (2016). Unlocking the Traumatic through the Psychedelic in One Flew over the Cuckoo’s Nest.
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Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors

/ MDMA, Neuroscience, Papers, Publications, Substance Use Disorder / / , ,

Abstract

Rationale: The synthetic phenethylamines are recreational drugs known to produce psychostimulant effects. However, their abuse potential has not been widely studied.
Objectives: Here, we investigated the rewarding and the hallucinatory effects of 2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA) in comparison with the classical 3,4-methylenedioxymethamphetamine (MDMA). In addition, the role of serotonin 5-HT2-like receptor on the abovementioned effects was evaluated.
Methods: Zebrafish were intramuscularly (i.m.) treated with a wide range of doses of DOB (0.1–20 mg/kg), PMA (0.0005–2 mg/kg), or MDMA (0.5–160 mg/kg). Animals were submitted to a conditioned place preference (CPP) task, to investigation of the rewarding properties, and to the evaluation of hallucinatory behavior in terms of appearance of a trance-like behavior. The serotonin 5-HT2 subtype receptor antagonist ritanserin (0.025–2.5 mg/kg) in association with the maximal effective dose of MDMA, DOB, and PMA was given i.m., and the effect on CPP or hallucinatory behavior was evaluated.
Results: MDMA and its derivatives exhibited CPP in a biphasic fashion, being PMA the most potent. This effect was accompanied, for DOB (2 mg/kg) and PMA (0.1 mg/kg), by a trance-like hallucinatory behavior. MDMA at a high dose as 160 mg/kg did not induce any hallucinatory behavior. Ritanserin significantly blocked the rewarding and hallucinatory effects suggesting the involvement of serotonin 5HT2 subtype receptor.
Conclusion: Collectively, these findings demonstrate for the first time that the rewarding properties of DOB and PMA are accompanied by hallucinatory behavior through a serotonergic system and reinforce zebrafish as an emerging experimental model for screening new hallucinogens.
Ponzoni, L., Daniela, B., & Sala, M. (2016). Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: role of serotonin 5HT2-type receptors. Psychopharmacology, 1-9. http://dx.doi.org/10.1007/s00213-016-4352-4
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Letter to the Editor: R-ketamine: a rapid-onset and sustained antidepressant without risk of brain toxicity

/ Depressive Disorders, Ketamine, Papers, Psychology, Publications / /

Hashimoto, K. (2016). Letter to the Editor: R-ketamine: a rapid-onset and sustained antidepressant without risk of brain toxicity. Psychological medicine, 1. http://dx.doi.org/10.1017/S0033291716000969
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Women and Psychedelics: Cycles, Care, and Conditions - October 23rd

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