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Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

September 28, 2011 / Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By / , , ,

Abstract

The serotonin-2A receptor (5-HT2AR) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT2AR or 5-HT1AR agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT2A/2CR antagonist ketanserin. A total of 16 healthy participants received placebo,ketanserin (40 mg p.o.), psilocybin (260 µg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT2AR stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT2AR system.

Quednow, B. B., Kometer, M., Geyerand, M. A., & Vollenweider, F. X. (2012). Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers. Neuropsychopharmacology, 37, 630-640. http://dx.doi.org/10.1038/npp.2011.228
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Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness

September 28, 2011 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , ,

Abstract

A large body of evidence, including longitudinal analyses of personality change, suggests that core personality traits are predominantly stable after age 30. To our knowledge, no study has demonstrated changes in personality in healthy adults after an experimentally manipulated discrete event. Intriguingly, double-blind controlled studies have shown that the classic hallucinogen psilocybin occasions personally and spiritually significant mystical experiences that predict long-term changes in behaviors, attitudes and values. In the present report we assessed the effect of psilocybin on changes in the five broad domains of personality – Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness. Consistent with participant claims of hallucinogen-occasioned increases in aesthetic appreciation, imagination, and creativity, we found significant increases in Openness following a high-dose psilocybin session. In participants who had mystical experiences during their psilocybin session, Openness remained significantly higher than baseline more than 1 year after the session. The findings suggest a specific role for psilocybin and mystical-type experiences in adult personality change.

MacLean, K. A., Johnson, M. W., & Griffiths, R. R. (2011). Mystical Experiences Occasioned by the Hallucinogen Psilocybin Lead to Increases in the Personality Domain of Openness. Journal of Psychopharmacology, 25(11), 1453-1461. http://dx.doi.org/10.1177/0269881111420188
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Revisiting Wasson's Soma: Exploring the Effects of Preparation on the Chemistry of Amanita Muscaria

September 20, 2011 / Biology & Ethnobotany, Humanities & Art, Mushrooms / Psilocybin, Papers, Publications / By /

Abstract

In 1968 R. Gordon Wasson first proposed his groundbreaking theory identifying Soma, the hallucinogenic sacrament of the Vedas, as the Amanita muscaria mushroom. While Wasson’s theory has garnered acclaim, it is not without its faults. One omission in Wasson’s theory is his failure to explain how pressing and filtering Soma, as described in the Rig Veda, supports his theory of Soma’s identity. Several critics have reasoned that such preparation should be unnecessary if equivalent results can be obtained by consuming the raw plant, as is done with other psychoactive mushrooms. In order to address these specific criticisms over 600 anecdotal accounts of Amanita muscaria inebriation were collected and analyzed to determine the impact of preparation on Amanita muscaria’s effects. The findings of this study demonstrated that the effects of Amanita muscaria were related to the type of preparation employed, and that its toxic effects were considerably reduced by preparations that paralleled those described for Soma in the Rig Veda. While unlikely to end debate over the identity of Soma, this study’s findings help to solidify the foundation of Wasson’s theory, and also to demonstrate the importance of preparation in understanding and uncovering the true identity of Soma.

Feeney, K. (2010). Revisiting Wasson’s Soma: Exploring the Effects of Preparation on the Chemistry of Amanita Muscaria. Journal of psychoactive drugs, 42(4), 499-506. https://dx.doi.org/ 10.1080/02791072.2010.10400712
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Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion

September 16, 2011 / Ayahuasca, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

The hallucinogenic brew Ayahuasca, a rich source of serotonergic agonists and reuptake inhibitors, has been used for ages by Amazonian populations during religious ceremonies. Among all perceptual changes induced by Ayahuasca, the most remarkable are vivid “seeings.” During such seeings, users report potent imagery. Using functional magnetic resonance imaging during a closed-eyes imagery task, we found that Ayahuasca produces a robust increase in the activation of several occipital, temporal, and frontal areas. In the primary visual area, the effect was comparable in magnitude to the activation levels of natural image with the eyes open. Importantly, this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales. The activity of cortical areas BA30 and BA37, known to be involved with episodic memory and the processing of contextual associations, was also potentiated by Ayahuasca intake during imagery. Finally, we detected a positive modulation by Ayahuasca of BA 10, a frontal area involved with intentional prospective imagination, working memory and the processing of information from internal sources. Therefore, our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision, memory, and intention. By boosting the intensity of recalled images to the same level of natural image, Ayahuasca lends a status of reality to inner experiences. It is therefore understandable why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature.

de Aurojo, D. B., Ribeiro, S., Cecchi, G. A., Carvalho, F. M., Sanchez, T. A., Pinto, J. P., … Santos, A. C. (2011). Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion. Human Brain Mapping, 33(11), 2550-2560. http://dx.doi.org/10.1002/hbm.21381
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Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence

September 8, 2011 / Ketamine, Papers, Psychology, Publications, Substance Use Disorder / By / , , , , ,

Abstract

A prior study found that one ketamine-assisted psychotherapy session was significantly more effective than active placebo in promoting abstinence (Krupitsky et al. 2002). In this study of the efficacy of single versus repeated sessions of ketamine-assisted psychotherapy in promoting abstinence in people with heroin dependence, 59 detoxified inpatients with heroin dependence received a ketamine-assisted psychotherapy (KPT) session prior to their discharge from an addiction treatment hospital, and were then randomized into two treatment groups. Participants in the first group received two addiction counseling sessions followed by two KPT sessions, with sessions scheduled on a monthly interval (multiple KPT group). Participants in the second group received two addiction counseling sessions on a monthly interval, but no additional ketamine therapy sessions (single KPT group). At one-year follow-up, survival analysis demonstrated a significantly higher rate of abstinence in the multiple KPT group. Thirteen out of 26 subjects (50%) in the multiple KPT group remained abstinent, compared to 6 out of 27 subjects (22.2%) in the single KPT group (p < 0.05). No differences between groups were found in depression, anxiety, craving for heroin, or their understanding of the meaning of their lives. It was concluded that three sessions of ketamine-assisted psychotherapy are more effective than a single session for the treatment of heroin addiction.

Krupitsky, E. M., Burakov, A. M., Dunaevsky, I. V., Romanova, T. N., Slavina, T. Y., & Grinenko, A. Y. (2007). Single versus repeated sessions of ketamine-assisted psychotherapy for people with heroin dependence. Journal of psychoactive drugs, 39(1), 13-19. https://dx.doi.org/10.1080/02791072.2007.10399860
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Reassessing the cultural and psychopharmacological significance of Banisteriopsis caapi: preparation, classification and use among the Piaroa of Southern Venezuela

September 8, 2011 / Anthropology & Sociology, Ayahuasca, Biology & Ethnobotany, Papers, Publications / By

Abstract

Recent attention to the monoamine oxidase inhibiting properties of Banisteriopsis caapi‘s harmala alkaloids has precluded a balanced assessment of B. caapi‘s overall significance to indigenous South American societies. Relatively little attention has been paid to the cultural contexts, local meanings and patterns of use of B. caapi among snuff-using societies, such as the Piaroa, who do not prepare decoctions containing N,N-dimethyltryptamine (DMT) admixtures. This article reviews the psychopharmacological literature on B. caapi in light of recent ethnographic work conducted among the Piaroa of southern Venezuela. Piaroa shamans use only B. caapi’s cambium, identify at least five distinct varieties of B. caapi, and emphasise the plant’s importance for heightening empathy. Some Piaroa people also attribute a range of extra-shamanic uses to B. caapi, including as a stimulant and hunting aid. In light of the psychopharmacological complexity of harmala alkaloids, and ethnographic evidence for a wide range of B. caapi uses, future research should reconsider B. caapi‘s cultural heritage and psychopharmacological potential as a stimulant and antidepressant-like substance.

Rodd, R. (2008). Reassessing the cultural and psychopharmacological significance of Banisteriopsis caapi: preparation, classification and use among the Piaroa of Southern Venezuela. Journal of psychoactive drugs, 40(3), 301-307. 10.1080/02791072.2008.10400645
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MDMA-Assisted Psychotherapy Using Low Doses in a Small Sample of Women with Chronic Posttraumatic Stress Disorder

September 8, 2011 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , , ,

Abstract

The purpose of this study was to investigate the safety of different doses of MDMA-assisted psychotherapy administered in a psychotherapeutic setting to women with chronic PTSD secondary to a sexual assault, and also to obtain preliminary data regarding efficacy. Although this study was originally planned to include 29 subjects, political pressures led to the closing of the study before it could be finished, at which time only six subjects had been treated. Preliminary results from those six subjects are presented here. We found that low doses of MDMA (between 50 and 75 mg) were both psychologically and physiologically safe for all the subjects. Future studies in larger samples and using larger doses are needed in order to further clarify the safety and efficacy of MDMA in the clinical setting in subjects with PTSD.

Bouso, J. C., Doblin, R., Farré, M., Alcázar, M. Á., & Gómez-Jarabo, G. (2008). MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. Journal of psychoactive drugs, 40(3), 225-236., 10.1080/02791072.2008.10400637
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Combating substance abuse with ibogaine: pre- and posttreatment recommendations and an example of successive model fitting analyses

September 7, 2011 / Iboga / Ibogaine, Papers, Psychology, Publications, Substance Use Disorder / By / ,

Abstract

Ibogaine is an indole alkaloid derived from the root bark of the African shrub Tabernan the iboga and it has been used for many years as a medicinal and ceremonial agent in West Central Africa. Furthermore, both anecdotal observations and recent studies suggest that ibogaine alleviates withdrawal symptoms and reduces drug cravings. Although ibogaine articles typically include information bearing on the duration of drug abstinence following treatment, little if any attention is given to the psychological and environmental factors that might facilitate a positive treatment outcome. Hence, a major purpose of the present review is to suggest a number of theory-driven, pretreatment and posttreatment recommendations that have good potential for enhancing ibogaine’s effectiveness. The second major purpose of this review is to demonstrate, through a reanalysis of previously published results, the utility of conducting successive model fitting analyses on ibogaine treatment data. Such analyses are useful for determining both the strength and form of the association between pre-ibogaine treatment variables and post-ibogaine treatment outcomes. Finally, in order to facilitate future quantitative reviews, the authors recommend that a minimum set of patient- and treatment-related variables be included in all ibogaine publications involving human participants.

Hittner, J. B., & Quello, S. B. (2004). Mechanisms of antiaddictive actions of ibogaine. Journal of Psychoactive Drugs, 36(2), 191-199. http://dx.doi.org/10.1080/02791072.2004.10399729
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Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis

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

Abstract

A total of 32 Banisteriopsis caapi samples and 36 samples of Psychotria viridis were carefully collected from different plants on the same day from 22 sites throughout Brazil for phytochemical analyses. A broad range in alkaloid distribution was observed in both sample sets. All B. caapi samples had detectable amounts of harmine, harmaline and tetrahydroharmine (THH), while some samples of P. viridis had little or no detectable levels of N,N-dimethyltryptamine (DMT). Leaves of P. viridis were also collected from one plant and analyzed for DMT throughout a 24-hour cycle.

Callaway, J. C., Brito, G. S., & Neves, E. S. (2005). Phytochemical analyses of Banisteriopsis caapi and Psychotria viridis. Journal of psychoactive drugs, 37(2), 145-150. 10.1080/02791072.2005.10399795
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Bringing Ayahuasca to the Clinical Research Laboratory

September 7, 2011 / Ayahuasca, Neuroscience, Papers, Publications / By / ,

Abstract

Since the winter of 1999, the authors and their research team have been conducting clinical studies involving the administration of ayahuasca to healthy volunteers. The rationale for conducting this kind of research is twofold. First, the growing interest of many individuals for traditional indigenous practices involving the ingestion of natural psychotropic drugs such as ayahuasca demands the systematic study of their pharmacological profiles in the target species, i.e., human beings. The complex nature of ayahuasca brews combining a large number of pharmacologically active compounds requires that research be carried out to establish the safety and overall pharmacological profile of these products. Second, the authors believe that the study of psychedelics in general calls for renewed attention. Although the molecular and electrophysiological level effects of these drugs are relatively well characterized, current knowledge of the mechanisms by which these compounds modify the higher order cognitive processes in the way they do is still incomplete, to say the least. The present article describes the development of the research effort carried out at the Autonomous University of Barcelona, commenting on several methodological aspects and reviewing the basic clinical findings. It also describes the research currently underway in our laboratory, and briefly comments on two new studies we plan to undertake in order to further our knowledge of the pharmacology of ayahuasca.

Riba, J., & Barbanoj, M. J. (2005). Bringing ayahuasca to the clinical research laboratory. Journal of Psychoactive Drugs, 37(2), 219-230. 10.1080/02791072.2005.10399804
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