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Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep

April 1, 2016 / Papers, Publications, Salvia / Salvinorin A / By / , , , , ,

Abstract

Although Salvia divinorum is traditionally known as a ‘mind-altering’ or psychoactive herb used, among others things, as a tranquilizer, this property has not been validated with regard to its efficacy and safety. The objective of this study is to provide evidence for the sedative effects of S. divinorum and discriminate the nature of the responsible constituents by examining different experimental models. A battery of tests, including the open-field, hole-board, exploration cylinder, plus-maze and sodium pentobarbital-induced hypnosis potentiation, were used in mice after administration of non-polar, medium polar and/or polar extracts of the plant (10, 30 and 100 mg/kg). Polysomnographic analysis in rats receiving an active medium polar extract (10 and 100 mg/kg) containing salvinorins was also assessed to study the effects of this plant on sleep architecture. All tested extracts produced significant sedative-like responses, although those of the medium polar extract were more pronounced in mice. The sedative effect of this latter extract, which contains a mixture of salvinorins, caused fragmented sleep architecture in rats by diminishing rapid eye movement (REM) sleep and increased the quiet awake stage at 10 and 100 mg/kg. Our results provide evidence that S. divinorum exhibits sedative-like depressant properties that alter physiological sleep architecture.

González‐Trujano, M. E., Brindis, F., López‐Ruiz, E., Ramírez‐Salado, I., Martínez, A., & Pellicer, F. (2016). Depressant Effects of Salvia divinorum Involve Disruption of Physiological Sleep. Phytotherapy Research. http://dx.doi.org/10.1002/ptr.5617

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The routes of a plant: ayahuasca and the global networks of Santo Daime

March 31, 2016 / Anthropology & Sociology, Ayahuasca, Papers, Publications / By / ,

Abstract

This paper examines the Santo Daime religion, the Amazonian town of Céu do Mapiá which is one of its primary spiritual centres, and Ayahuasca, a key sacrament of the Santo Daime religion. The small village in the Amazon demonstrates the active outreach by a place which functions as a nexus of international and intercontinental flows of substances, bodies and meanings. The power of place is entwined with the story of religious belief and practice, which in turn depends on a tropical vine, Banisteriopsis caapi. In this networking process, we find a confluence of human agency with more-than-human agency, as well as the modalities of religious experience, crossing and dwelling. It is demonstrated that religious networking can be understood in terms of three forms of crossing (terrestrial, corporeal and cosmic) held together by the power of place (Mapiá and other subsidiary spiritual centres). In addition, three aspects of the ‘ayahuasca network’ are treated in depth: religious diffusion and adaptation, interaction with environmental movements and ideologies and contestation with legal structures and processes surrounding international drug traffic and the use of psychoactive substances.

Lowell, J. T., & Adams, P. C. (2016). The routes of a plant: ayahuasca and the global networks of Santo Daime. Social & Cultural Geography, 1-21. http://dx.doi.org/10.1080/14649365.2016.1161818
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Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

March 28, 2016 / Iboga / Ibogaine, Papers, Publications / By / , , , ,

Abstract

Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

Rubi, L., Eckert, D., Boehm, S., Hilber, K., & Koenig, X. (2016). Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Cardiovascular Toxicology, 1-4. http://dx.doi.org/10.1007/s12012-016-9366-y

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Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans

March 25, 2016 / Ayahuasca, Neuroscience, Papers, Publications / By / , , , , , ,

Abstract

Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants, Banisteriopsis caapi and Psychotria viridis. It contains the psychedelic 5-HT2A and sigma-1 agonist N,N-dimethyltryptamine (DMT) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties. Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor, the molecular target of classical psychedelics, this has not been tested experimentally. Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans. We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind randomized placebo-controlled study involving the oral administration of ayahuasca (0.75mg DMT/kg body weight) and the 5-HT2A antagonist ketanserin (40mg). Twelve healthy, experienced psychedelic users (5 females) participated in four experimental sessions in which they received the following drug combinations: placebo+placebo, placebo+ayahuasca, ketanserin+placebo and ketanserin+ayahuasca. Ayahuasca induced EEG power decreases in the delta, theta and alpha frequency bands. Current density in alpha-band oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca. Pretreatment with ketanserin inhibited neurophysiological modifications, reduced the correlation between alpha and visual effects, and attenuated the intensity of the subjective experience. These findings suggest that despite the chemical complexity of ayahuasca, 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans.

Valle, M., Maqueda, A. E., Rabella, M., Rodríguez-Pujadas, A., Antonijoan, R. M., Romero, S., … & Feilding, A. (2016). Inhibition of alpha oscillations through serotonin-2A receptor activation underlies the visual effects of ayahuasca in humans. European Neuropsychopharmacology. http://dx.doi.org/10.1016/j.euroneuro.2016.03.012

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Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies

March 24, 2016 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, Papers, Psychology, Publications / By / , , ,

Abstract

Objective:

To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline).

Methods:

Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection.

Results:

Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression.

Conclusion:

Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.

dos Santos, R. G., Osório, F. L., Crippa, J. A. S., & Hallak, J. E. (2016). Antidepressive and anxiolytic effects of ayahuasca: a systematic literature review of animal and human studies. Revista Brasileira de Psiquiatria, 38(1), 65-72. http://dx.doi.org/10.1590/1516-4446-2015-1701
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Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide

March 24, 2016 / Depressive Disorders, LSD, Neuroscience, Papers, Psychology, Publications / By / , , , , , ,

Abstract

This paper reports on the effects of LSD on mental time travel during spontaneous mentation. Twenty healthy volunteers participated in a placebo-controlled crossover study, incorporating intravenous administration of LSD (75 μg) and placebo (saline) prior to functional magnetic resonance imaging (fMRI). Six independent, blind judges analysed mentation reports acquired during structured interviews performed shortly after the functional magnetic resonance imaging (fMRI) scans (approximately 2.5 h post-administration). Within each report, specific linguistic references to mental spaces for the past, present and future were identified. Results revealed significantly fewer mental spaces for the past under LSD and this effect correlated with the general intensity of the drug’s subjective effects. No differences in the number of mental spaces for the present or future were observed. Consistent with the previously proposed role of the default-mode network (DMN) in autobiographical memory recollection and ruminative thought, decreased resting-state functional connectivity (RSFC) within the DMN correlated with decreased mental time travel to the past. These results are discussed in relation to potential therapeutic applications of LSD and related psychedelics, e.g. in the treatment of depression, for which excessive reflection on one’s past, likely mediated by DMN functioning, is symptomatic.

Speth, J., Speth, C., Kaelen, M., Schloerscheidt, A. M., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2016). Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide. Journal of psychopharmacology (Oxford, England), 30(4), 344. http://dx.doi.org/10.1177/0269881116628430

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Lysergic acid diethylamide: a drug of ‘use’?

March 23, 2016 / Anxiety Disorders / PTSD, LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

Lysergic acid diethylamide (LSD), described as a classical hallucinogen, began its journey from the middle of the last century following an accidental discovery. Since then, it was used as a popular and notorious substance of abuse in various parts of the world. Its beneficial role as an adjunct to psychotherapy was much unknown, until some ‘benevolent’ experiments were carried out over time to explore some of its potential uses. But, many of its effects were unclear and seemed to be a psychedelic enigma. In this review article, we have described the receptor pharmacology, mechanism of action, effects and adverse effects of LSD on the normal body system. We have also highlighted its addictive potentials and the chances of developing tolerance. We have assimilated some of the interesting therapeutic uses of this drug, such as an antianxiety agent, a creativity enhancer, a suggestibility enhancer, and a performance enhancer. We have also described LSD to be successfully used in drug and alcohol dependence, and as a part of psychedelic peak therapy in terminally ill patients. The relevant chronological history and literature in the light of present knowledge and scenarios have been discussed. Based on available evidence, LSD could be tried therapeutically in certain specific conditions under controlled settings. But as we mention, due to all the safety concerns, the use of this nonaddictive ‘entheogen’ in actual practice warrants a lot of expertise, caution, cooperation and ethical considerations.

Das, S., Barnwal, P., Ramasamy, A., Sen, S., & Mondal, S. (2016). Lysergic acid diethylamide: a drug of ‘use’?. Therapeutic Advances in Psychopharmacology, 2045125316640440.
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Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models

March 22, 2016 / LSD, Mushrooms / Psilocybin, Papers, Publications / By / ,

Abstract

After decades of sociopolitical obstacles, the field of psychiatry is experiencing a revived interest in the use of hallucinogenic agents to treat brain disorders. Along with the use of ketamine for depression, recent pilot studies have highlighted the efficacy of classic serotonergic hallucinogens, such as lysergic acid diethylamide and psilocybin, in treating addiction, post-traumatic stress disorder, and anxiety. However, many basic pharmacological and toxicological questions remain unanswered with regard to these compounds. In this study, we discuss psychedelic medicine as well as the behavioral and toxicological effects of hallucinogenic drugs in zebrafish. We emphasize this aquatic organism as a model ideally suited to assess both the potential toxic and therapeutic effects of major known classes of hallucinogenic compounds. In addition, novel drugs with hallucinogenic properties can be efficiently screened using zebrafish models. Well-designed preclinical studies utilizing zebrafish can contribute to the reemerging treatment paradigm of psychedelic medicine, leading to new avenues of clinical exploration for psychiatric disorders.

Kyzar, E. J., & Kalueff, A. V. (2016). Exploring Hallucinogen Pharmacology and Psychedelic Medicine with Zebrafish Models. Zebrafish. http://dx.doi.org/10.1089/zeb.2016.1251

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