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Various alkaloid profiles in decoctions of Banisteriopsis caapi

September 7, 2011 / Ayahuasca, Biology & Ethnobotany, Papers, Pharmacology & Chemistry, Publications / By /

Abstract

Twenty nine decoctions of Banisteriopsis caapi from four different sources and one specimen of B. caapi paste were analyzed for N,N-dimethyltryptamine (DMT), tetrahydroharmine (THH), harmaline and harmine. Other plants were also used in the preparation of these products, typically Psychotria viridis, which provides DMT. There were considerable variations in alkaloid profiles, both within and between sample sources. DMT was not detected in all samples. Additional THH may be formed from both harmine and harmaline during the preparation of these products. The alkaloid composition of one decoction sample did not change significantly after standing at room temperature for 80 days, but the initial acidic pH was neutralized by natural fermentation after 50 days.

Callaway, J. C. (2005). Various alkaloid profiles in decoctions of Banisteriopsis caapi. Journal of Psychoactive Drugs, 37(2), 151-155. 10.1080/02791072.2005.10399796
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Snuff synergy: preparation, use and pharmacology of yopo and Banisteriopsis caapi among the Piaroa of southern Venezuela

September 6, 2011 / Ayahuasca, Biology & Ethnobotany, Papers, Pharmacology & Chemistry, Publications / By /

Abstract

Current understanding of the preparation and use of yopo, a hallucinogenic snuff made from the ground seeds of the Anadenanthera peregrina tree, has departed little from the accounts of scientists and travelers made over a century ago. Schultes and others have made refinements to these early accounts. While several scholars have drawn attention to the fact that little ethnographic work has been conducted to assess the ethnobotanical diversity and cultural framework of the snuff hallucinogen complex, few subsequent studies deal with botanical variations in preparation and use. This article contrasts historical accounts of yopo preparation with ethnographic data I have recently collected among the Piaroa of southern Venezuela to demonstrate one way in which yopo preparation and use deviates from the basic model established by Humboldt, Spruce and Safford. Piaroa shamans include B. caapi cuttings in the preparation of yopo and consume doses of B. caapi prior to snuff inhalation concomitant with the strength of visions desired for particular tasks. I argue that the combined use of yopo and B. caapi by Piaroa shamans is pharmacologically and ethnobotanically significant, and substantiates claims of the use of admixtures in snuff; further ethnographic investigation of the snuff hallucinogen complex is necessary.

Rodd, R. (2002). Snuff synergy: preparation, use and pharmacology of yopo and Banisteriopsis caapi among the Piaroa of southern Venezuela. Journal of psychoactive drugs, 34(3), 273-279. 10.1080/02791072.2002.10399963
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A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department

September 1, 2011 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / ,

Abstract

We examined the preliminary feasibility, tolerability and efficacy of single-dose, intravenous (i.v.) ketamine in depressed emergency department (ED) patients with suicide ideation (SI). Fourteen depressed ED patients with SI received a single i.v. bolus of ketamine (0.2 mg/kg) over 1–2 min. Patients were monitored for 4 h, then re-contacted daily for 10 d. Treatment response and time to remission were evaluated using the Montgomery–Asberg Depression Rating Scale (MADRS) and Kaplan–Meier survival analysis, respectively. Mean MADRS scores fell significantly from 40.4 (S.E.M.=1.8) at baseline to 11.5 (S.E.M.=2.2) at 240 min. Median time to MADRS score f10 was 80 min (interquartile range 0.67–24 h). SI scores (MADRS item 10) decreased significantly from 3.9 (S.E.M.=0.4) at baseline to 0.6 (S.E.M.=0.2) after 40 min post-administration ; SI improvements were sustained over 10 d. These data provide preliminary, open-label support for the feasibility and efficacy of ketamine as a rapid-onset antidepressant in the ED.

Larkin, G. L., & Beautrais, A. L. (2011). A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. International Journal of Neuropsychopharmacology, 1127-1131. http://dx.doi.org/10.1017/S1461145711000629

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Heaven and Hell—A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden

August 29, 2011 / Papers, Psychology, Publications / By / ,

Abstract

The psychoactive substance 4-HO-MET (4-hydroxy-N-methyl-N-ethyltryptamine) with psychedelic qualities is one of many legal so-called Internet drugs. The aim of this qualitative study was to establish an understanding of what characterizes its recreational use. Very little is known about the effects of this substance. Twenty-five anonymous Swedish experience reports (from persons aged 18–30 years) from public Internet forums were analyzed using the Empirical Phenomenological Psychological Method. The analysis produced 37 categories that were compiled into nine general themes: (1) motivation, preparation and expectation; (2) initial effects; (3) change of perception; (4) unfiltered awareness and intensified flow of information; (5) lateral cognition; (6) border between subject and object is erased; (7) heaven; (8) hell; and (9) subsiding effects. An understanding of the chronological happenings, called The Process, appeared out of the general structure. Drastic changes in cognitive, emotional and bodily functions were described. The motivation for use seemed to be driven by a strong curiosity. The experiences shifted between “heaven” and “hell,” but participants appeared satisfied and ready to repeat the experience. The experiences described show great similarity with classic psychedelic substances as LSD or psilocybin. More research is needed about health hazards or possible therapeutic potentials.

Kjellgren, A., & Soussan, C. (2011). Heaven and Hell—A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden. Journal of Psychoactive Drugs, 43(3), 211-219. http://dx.doi.org/10.1080/02791072.2011.605699
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Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain

August 1, 2011 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

A growing body of evidence has pointed to the N-methyl-d-aspartate (NMDA) receptor antagonists as a potential therapeutic target for the treatment of major depression. The present study investigated the possibility of synergistic interactions between antidepressant imipramine with the uncompetitive NMDA receptor antagonist ketamine. Wistar rats were acutely treated with ketamine (5 and 10 mg/kg) and imipramine (10 and 20 mg/kg) and then subjected to forced swimming tests. The cAMP response element bindig (CREB) and brain-derived neurotrophic factor (BDNF) protein levels and protein kinase C (PKC) and protein kinase A (PKA) phosphorylation were assessed in the prefrontal cortex, hippocampus and amygdala by imunoblot. Imipramine at the dose of 10 mg/kg and ketamine at the dose of 5 mg/kg did not have effect on the immobility time; however, the effect of imipramine (10 and 20 mg/kg) was enhanced by both doses of ketamine. Ketamine and imipramine alone or in combination at all doses tested did not modify locomotor activity. Combined treatment with ketamine and imipramine produced stronger increases of CREB and BDNF protein levels in the prefrontal cortex, hippocampus and amygdala, and PKA phosphorylation in the hippocampus and amygdala and PKC phosphorylation in prefrontal cortex. The results described indicate that co-administration of antidepressant imipramine with ketamine may induce a more pronounced antidepressant activity than treatment with each antidepressant alone. This finding may be of particular importance in the case of drug-resistant patients and could suggest a method of obtaining significant antidepressant actions whilst limiting side effects.

Réus, G. Z., Stringari, R. B., Ribeiro, K. F.,  Ferraro, A. K.,  Vitto, M. F., Cesconetto, P., … Quevedo, J. (2011). Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain. Behavioural Brain Research, 221(1), 166-171. http://dx.doi.org/10.1016/j.bbr.2011.02.024
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Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

June 15, 2011 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , ,

Abstract

Rationale: This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes, mood, and behavior.

Objectives: This double-blind study evaluated psilocybin (0, 5, 10, 20, 30 mg/70 kg, p.o.) administered under supportive conditions.

Methods: Participants were 18 adults (17 hallucinogennaïve). Five 8-h sessions were conducted individually for each participant at 1-month intervals. Participants were randomized to receive the four active doses in either ascending or descending order (nine participants each). Placebo was scheduled quasi-randomly. During sessions, volunteers used eyeshades and were instructed to direct their attention inward. Volunteers completed questionnaires assessing effects immediately after and 1 month after each session, and at 14 months follow-up.

Results: Psilocybin produced acute perceptual and subjective effects including, at 20 and/or 30 mg/70 kg, extreme anxiety/fear (39% of volunteers) and/or mystical-type experience (72% of volunteers). One month after sessions at the two highest doses, volunteers rated the psilocybin experience as having substantial personal and spiritual significance, and attributed to the experience sustained positive changes in attitudes, mood, and behavior, with the ascending dose sequence showing greater positive effects. At 14 months, ratings were undiminished and were consistent with changes rated by community observers. Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose, with the lowest dose showing significant effects.

Conclusions: Under supportive conditions, 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes, mood, and behavior. Implications for therapeutic trials are discussed.

Griffiths, R. R., Johnson, M. W., Richards, W. A., Richards, B. D., McCann, U., & Jesse, R. (2011). Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology, 218(4), 649-665. http://dx.doi.org/10.1007/s00213-011-2358-5
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In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in MDMA and Hallucinogen Users

June 6, 2011 / Ayahuasca, DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications, Salvia / Salvinorin A / By / , , , , , ,

Abstract

Context:
Both hallucinogens and 3,4-methylenedioxy-methamphetamine (MDMA or “ecstasy”) have direct agonistic effects on postsynaptic serotonin 2A receptors, the key site for hallucinogenic actions. In addition, MDMA is a potent releaser and reuptake inhibitor of presynaptic serotonin.

Objective:
To assess the differential effects of MDMA and hallucinogen use on cerebral serotonin transporter (SERT) and serotonin2Areceptor binding.

Design:
A positron emission tomography study of 24 young adult drug users and 21 nonusing control partici-pants performed with carbon 11 (11C)–labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzo-nitrile (DASB) and fluorine 18 (18F)–labeled altanserin, respectively. Scans were performed in the user group after a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n = 10) and MDMA-preferring users (n = 14).

Participants:
Twenty-four young adult users of MDMA and/or hallucinogenic drugs and 21 nonusing controls.

Main Outcome Measures:
In vivo cerebral SERT and serotonin 2A receptor binding.

Results:
Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, −56%; pallidostriatum, −19%; and amygdala, −32%); no significant changes were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of life-time MDMA exposures, and the time of abstinence from MDMA was positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin 2A receptor binding in the serotonin 2A receptor agonist users (both user groups) was also detected.

Conclusions
We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin 2A receptor agonistic actions, we conclude that the negative association between MDMA use and cerebral SERT binding is mediated through a direct presynaptic MDMA effect rather than by the serotonin 2A agonistic effects of MDMA. Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.

Erritzoe, D., Frokjaer, V. G., Holst, K. K., Christoffersen, M., Johansen, S. S., Svarer, C., … Knudsen, G. M. (2011). In Vivo Imaging of Cerebral Serotonin Transporter and Serotonin 2A Receptor Binding in 3,4-Methylenedioxymethamphetamine (MDMA or “Ecstasy”) and Hallucinogen Users. Archives of General Psychiatry, 68(6), 562-576. http://dx.doi.org/10.1001/archgenpsychiatry.2011.56
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β-Carboline Compounds, Including Harmine, Inhibit DYRK1A and Tau Phosphorylation at Multiple Alzheimer's Disease-Related Sites

May 6, 2011 / Ayahuasca, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

Harmine, a β-carboline alkaloid, is a high affinity inhibitor of the dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) protein. The DYRK1A gene is located within the Down Syndrome Critical Region (DSCR) on chromosome 21. We and others have implicated DYRK1A in the phosphorylation of tau protein on multiple sites associated with tau pathology in Down Syndrome and in Alzheimer’s disease (AD). Pharmacological inhibition of this kinase may provide an opportunity to intervene therapeutically to alter the onset or progression of tau pathology in AD. Here we test the ability of harmine, and numerous additional β-carboline compounds, to inhibit the DYRK1A dependent phosphorylation of tau protein on serine 396, serine 262/serine 356 (12E8 epitope), and threonine 231 in cell culture assays and in vitro phosphorylation assays. Results demonstrate that the β-carboline compounds (1) potently reduce the expression of all three phosphorylated forms of tau protein, and (2) inhibit the DYRK1A catalyzed direct phosphorylation of tau protein on serine 396. By assaying several β-carboline compounds, we define certain chemical groups that modulate the affinity of this class of compounds for inhibition of tau phosphorylation.

Frost, D., Meechoovet, B., Wang, T., Gately, S., Giorgetti, M., Shcherbakova, I., & Dunckley, T. (2011). β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer’s disease-related sites. PLoS One, 6(5). https://dx.doi.org/10.1371/journal.pone.0019264

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Ayahuasca, Entheogenic Education & Public Policy

April 18, 2011 / Anthropology & Sociology, Ayahuasca, Papers, Publications / By /

Abstract

Ayahuasca is an entheogenic decoction prepared from two Amazonian plants containing controlled substances, including dimethyltryptamine. Traditionally drunk ritually (and revered as a healing “plant teacher”) by Amazonian indigenous and mestizo peoples, in the 20th century ayahuasca became a sacrament for several new Brazilian religions. One of these, the Santo Daime, has expanded into Canada, where in 2001 a Montreal-based chapter applied for a federal legal exemption to allow drinking of the brew in its rituals. This dissertation undertakes a critical policy analysis of Health Canada’s decision on the Santo Daime request, using government documents obtained through an Access to Information request as data. My goals are to illustrate how modern stereotypes about “drugs” and “drug abuse” in dominant public and political discourses may hinder well-informed policy decision making about ayahuasca, and to consider how entheogenic practices such as ayahuasca drinking are traditional indigenous ways of knowing that should be valued, rather than reflexively demonized and criminalized. My research method is a critical discourse analysis approach to policy analysis, an eclectic means of demonstrating how language contributes to conceptual frames and political responses to public policy issues. I combine insights from recent research on language, discourse and public policy to show how ayahuasca has become an unexpected policy conundrum for liberal democratic states attempting to balance competing interests of criminal justice, public health, and human rights such as religious freedom. I trace ayahuasca’s trajectory as a contemporary policy concern by sketching histories of psychoactive substance use, today’s international drug control regime, and the discursive foundations of its underlying drug war paradigm. Regarding Health Canada’s 2006 decision “in principle” to recommend exemption for the Daime brew, I critique how the government defined ayahuasca as a policy problem, what policy stakeholders it considered in its decision making, and what knowledge about ayahuasca it used. To conclude, I explore modern schooling’s systemic antipathy to wonder and awe, and propose that policy reforms allowing circumspect use of entheogens such as ayahuasca as cognitive tools may help stimulate re-enchantment and appreciation of the need to address human and planetary ecological predicaments of the 21st century.

Tupper, K. W. (2011). Ayahuasca, entheogenic education & public policy (Doctoral dissertation, University of British Columbia). 10.14288/1.0064622
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Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives

April 8, 2011 / Anthropology & Sociology, Ayahuasca, Papers, Psychology, Publications / By /

Abstract

In 2010, the Brazilian Government agency responsible for drug-related issues formulated official Resolutions that categorized the consumption of ayahuasca by pregnant women and children in the Santo Daime and Uniatildeo do Vegetal ayahuasca-based religions as an “exercise of parental rights.” Although ayahuasca groups do enjoy a relative degree of social legitimacy and formal legal recognition in Brazil, the participation of pregnant women and children nevertheless continues to provoke heated discussion. This article raises the main issues involved in the public debate over this subject. In the first part, a diverse group of biomedical and health specialists was consulted, and their opinions were briefly analyzed. In the second, a full interview with a follower of one branch of Santo Daime, mother of four children who took ayahuasca during all her pregnancies, and whose children all drink ayahuasca, is presented. Her interview reveals important cultural parameters of ayahuasca consumption. The article explores common themes and contradictions found between the biomedical, anthropological, and ayahuasca-users’ discourses. It raises central issues regarding the limits of freedom of religion and the state’s right to interfere in family matters. The following analysis also has implications regarding the role of science in influencing policy decisions on drug use.

Labate, B. C. (2011). Consumption of Ayahuasca by Children and Pregnant Women: Medical Controversies and Religious Perspectives. Journal of Psychoactive Drugs, 43(1), 27-35. http://dx.doi.org/10.1080/02791072.2011.566498
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