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Meta-analysis of executive functioning in ecstasy/polydrug users

Abstract

Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions – updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p < 0.001, I 2 = 82%], with a significant subgroup effect (χ 2 = 22.06, degrees of freedom = 3, p < 0.001, I 2 = 86.4%) demonstrating differential effects across executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p < 0.001, I 2 = 74%), switching (SMD = -0.19, 95% CI -0.36 to -0.02, Z = 2.16, p < 0.05, I 2 = 85%) and updating (SMD = -0.26, 95% CI -0.37 to -0.15, Z = 4.49, p < 0.001, I 2 = 82%). No differences were observed in inhibitory control. We conclude that this is the most comprehensive analysis of executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity.

Roberts, C. A., Jones, A., & Montgomery, C. (2016). Meta-analysis of executive functioning in ecstasy/polydrug users. Psychological medicine, 1-16. http://dx.doi.org/10.1017/S0033291716000258

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Ayahuasca: pharmacology, neuroscience and therapeutic potential

Abstract

Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one’s own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders.

Domínguez-Clavé, E., Soler, J., Elices, M., Pascual, J. C., Álvarez, E., de la Fuente Revenga, M., … & Riba, J. (2016). Ayahuasca: pharmacology, neuroscience and therapeutic potential. Brain Research Bulletin. http://dx.doi.org/10.1016/j.brainresbull.2016.03.002
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The History of MDMA as an Underground Drug in the United States, 1960-1979

Abstract

MDMA (3,4-methylenedioxy-methylamphetamine, a.k.a. “ecstasy”) was first synthesized in 1912 and resynthesized more than once for pharmaceutical reasons before it became a popular recreational drug. Partially based on previously overlooked U.S. government documentation, this article reconstructs the early history of MDMA as a recreational drug in the U.S. from 1960 to 1979. According to the literature, MDMA was introduced as a street drug at the end of the 1960s. The first forensic detection of MDMA “on the street” was reported in 1970 in Chicago. It appears that MDMA was first synthesized by underground chemists in search of “legal alternatives” for the closely related and highly sought-after drug MDA, which was scheduled under the Controlled Substances Act (CSA) in 1970. Until 1974, nearly all MDMA street samples seized came from the U.S. Midwest, the first “hot region” of MDMA use. In Canada, MDMA was first detected in 1974 and scheduled in 1976. From 1975 to 1979, MDMA was found in street samples in more than 10 U.S. states, the West Coast becoming the major “hot region” of MDMA use. Recreational use of MDMA spread across the U.S. in the early 1980s, and in 1985 it was scheduled under the CSA.

Passie, T., & Benzenhöfer, U. (2016). The history of MDMA as an underground drug in the United States, 1960–1979. Journal of psychoactive drugs48(2), 67-75., 10.1080/02791072.2015.1128580

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[Interview] Nicolas Langlitz: An Anthropologist in Psychedelia

The anthropologist as experimental subject. Courtesy of N. Langlitz

Neuropsychedelia: The Revival of Hallucinogen Research since the Decade of the Brain’, Nicolas Langlitz’s 2013 book on the resurgence of psychedelics research, offers a fascinating analysis of how psychedelics have once again become the object of human subject laboratory research. Langlitz identifies the ‘Decade of the Brain’ (think of the excitement over the human genome project in the 1990s) as legitimating a new framework for researching psychedelics, promising ‘moksha in the age of soma’. The book tracks psychopharmacological developments since the 1990s through two key sites – Franz X. Vollenweider’s human lab in Zurich and Mark A. Geyer’s animal lab in San Diego. Langlitz’s ethnographic material is interwoven with historical analysis and questions about psychedelics, technological mediation and mysticism, to offer a compelling account of how we have arrived at the present moment. Neuropsychedelia is a wonderful and insightful read for those interested in the growing field of psychedelics research, its origins and its stakes.

What surprised you when doing the research?

I started out from the assumption that there were these very different interpretations of psychedelic drug action: there is the notion of the ‘hallucinogen’ – drugs provoking hallucinations, a complete rupture with reality. It’s a misnomer because people hardly ever experience true hallucinations with psychedelics, but it informs the practice of model psychosis research. Then there was the psycholytic interpretation, especially in European psychotherapy, which assumed that these drugs provided access to the unconscious. The conceptualisation as ‘psychedelics’ is still running strong. It assumes that these substances allow us to commune with a cosmic mind that is infinitely larger than our individual minds. I had assumed that people would organise themselves in camps around these different interpretations. Philosophically, they really seemed quite incommensurable to me. So I was struck that every time I brought up this rationale for my research, of understanding how they’re navigating through these incommensurabilities, people shrugged and told me that they could entertain all these interpretations at the same time.

Why was that?

Psychedelics are not drugs doing just one thing. Their action is so contingent on the context in which they’re being used. They are actually opening up different things to different people. They can also close things down, as in the case of psychotic reactions, which do occur. Moreover, it’s a matter of dosage: the difference between psychedelic and psycholytic therapy has always been related to the amount of drugs that therapists administered to their clients. The different interpretations also have to do with different facets of these substances, and not just with the people who are looking at them. Psychedelics appear to have more faces than standard pharmacology would allow for.

Your chapter ‘Enacting Experimental Psychoses’ wonderfully conveys some of this. I think one often hears the difference between psycholytic and psychedelic experiences as being one of dosage, whereas the difference between mystical experience and psychotic experience is put down to quite entrenched differing presuppositions.

I’m sure that the difference between psycholytic and psychedelic experiences cannot be entirely reduced to dosage either. It will also be determined by diverging therapeutic philosophies that people with a psychoanalytic background will bring in comparison to people with a background in transpersonal psychology, for example.

More generally, anthropologists face the problem that people are often incoherent. We all entertain different beliefs, and unless you have an academic incentive to make them coherent so you can defend them at a conference, we live pretty well with our incoherent beliefs. If you’re using ethnography to pursue a philosophically-oriented anthropology, this can be puzzling or even frustrating, but it also makes this kind of fieldwork interesting. There are tensions between people’s different concepts, and you can explore these tensions through conversations. This kind of fieldwork is not just about obtaining data from so-called informants who already know the lay of the land. Instead I share questions with my interlocutors that are vital questions for them as much as for me, and we work through them together. In the case of Neuropsychedelia – especially the work I did in the Vollenweider lab – this worked beautifully. Two of the people I met there are still among my closest friends.

Could you say a little more about the incoherence you found in interpretations of the effects of psychedelics?

The substances are multi-faceted entities which allow for different uses and effects. Because the psychoactive effects of the drug are not just caused by the substance, but are emerging from its interactions with different people’s brains, different people’s personal situations and beliefs, with the settings in which the drug is taken, etc., you actually get a multiplicity of psychoactive effects. I don’t want to celebrate logical incoherence. I just think that what appears to be incoherent at first glance can be explained if you think about the way in which these substances work.

Do you understand the project of explaining them as one of ‘making them coherent’?

Yes. I think you can ultimately provide a coherent explanation for why people have different experiences with these substances. And you don’t have to think about it in terms of the idea that we’re living in multiple worlds or natures as some of my fellow anthropologists claim these days.

I enjoyed reading about your exchanges with the head of the Swiss lab, Franz Vollenweider. The way in which you come back to him at the end of the book to me suggested a respect, curiosity and affection for him. The same goes for some of the other characters. Is there anything more that you were looking for in them than interlocutors to think through these questions and tensions with?

First, the ways in which people relate to these psychedelics are quite intimate. Thinking more deeply with others about the experiences they produce requires relations of friendships. Friendship is really an epistemic precondition for this kind of intellectual work.

There is also an ethnographic dimension to these relations. I’m writing about people. I’m working through intellectual positions and contradictions by assigning them to different characters in the book. For me it was important to be generous regarding their different views, partly because initially they all seemed to hold a grain of truth. I think I empathised quite well with people in the field, even though they did not always empathise with each other. They had profound disagreements about what to make of these substances, which also provoked interpersonal tensions. I saw my role as that of a diplomat who can move between different camps and give everybody a sympathetic hearing.

Ethnographically, I was also interested in what place psychedelic drugs can have in our lives. So that’s not just a question about how to conceptualise these substances, but also about the practices and lives that people are actually living. The last chapter of Neuropsychedelia titled ‘Mystic Materialism’ is about the fraught relationship between science and personal experience. Many researchers went into psychedelic science because of their personal acquaintance with these drugs. But their own experiences are systematically marginalised in contemporary psychopharmacology.

Someone who crops up in the book in different guises is the German sociologist Max Weber (1864-1920). You work through his distinction between mystical and ascetic kinds of religious ethics. Then there’s the story of modernity’s disenchantment and science’s bureaucratisation that is threaded through the book. And finally the question of what it means for scientists to pursue a vocation. Were these just all separately useful concepts to pick up, or was there a reason that Weber kept coming back?

Weber struggled with the tensions inherent to modernity, which he saw turning into an iron cage, both in the form of bureaucratisation and in the form of a science that narrows its research problems down to very well-defined but ultimately meaningless questions. Questions such as whether a given substance activates the 5HT2A or 5HT1A receptor are extremely relevant to understanding its mechanism of action, but they don’t help you to solve the bigger questions of life which these drugs evoke experientially. I’ve tried to not refer to Weber as a theorist of modernity, but to weave him into the historical narrative itself. For example, by visiting Ascona in the 1910s, he interacted with a countercultural community in the Swiss Alps half a century before the term ‘counterculture’ was coined. This Heidelberg professor was trying to explore life beyond the ‘iron cage’ of the university apparatus. Following Weber’s analysis, the 1960s counterculture placed its psychedelic mysticism in opposition to the Protestant ethic of capitalism. So Weber is a presence throughout the history of this psychedelic research.

You discuss two virtues at the end of the book – diligence and surrender. It almost feels like the culmination of the book is advice to approach psychedelics on those terms. Could you say something about them?

In 1918, Weber urged every student at the University of Munich to search for the demon that holds the fibers of his very life. He also warned that nothing was gained from yearning alone and advised students to meet the demands of the day. I think this work ethic is very much in line with the revival of psychedelic research, which has broken with the countercultural ethos of Leary’s slogan “turn on, tune in, and drop out.” My plea for diligence is meant as a check against the excesses of mysticism.

By contrast, surrender is a virtue that is part of a mystical outlook. Instead of trying to transform the world in a high modernist spirit, you’re basically accepting that this is what the world is. It’s an anti-activist spirit. Surrender is important in relation to psychedelics because if you’re having a difficult experience with these drugs the only way out is not to struggle harder but to surrender – to give yourself up and to allow the experience to take over, and as you relax you basically manage to get out of the difficult situation again. I’m not at all saying that we should never try to make the world a better place, but sometimes acceptance would be wiser.

To develop friendships in this field is to develop friendships when the stakes are sometimes quite high as to how psychedelics and psychedelic-taking practices are understood and thought about. And a lot of that is because people have hopes about its legalisation – either under the form of medicalisation or wider availability. Often in the pharmacological and the broader scientific scholarships, research tends to have a kind of an ‘off-limits’ boundary-making around what should and shouldn’t be talked about openly in terms of personal experiences. How did you approach this issue?

There is always a political dimension to this research. However, neither Vollenweider’s nor Geyer’s lab was particularly politicised. People were primarily driven by curiosity, not activism. We had that in common. Of course, the field is larger than these two labs. Other people are a lot more passionate and outspoken about their political goals. But something I see in anthropology, where activism is well accepted, is that it can stifle and curtail intellectual conversations. So I was very happy to be able to work with people who didn’t have a strong agenda.

Personal experiences were still a slightly touchy subject, but they weren’t off limits. For example, I conducted an interview with Hans Jakob Dietschy, the government official in charge of controlled substances during the 1990s, and his scientific collaborator, the pharmacology professor Rudolph Brenneisen. At one point, they told me about a fight they had had about Brenneisen’s decision to serve as a test subject in his doctoral student’s psilocybin experiment. This anecdote was provided voluntarily but off the record. Since it fit very well into my discussion of the delegitimation of self-experiments, I used it anyways and sent them the whole subchapter of my PhD thesis to ask whether they would give me permission to use the episode if I presented it in its wider historical context. Both were perfectly fine with that.

Of course, there are also things that cannot be related publicly. But that’s not a problem specific to research on controlled substances. Ethnographers enter into communities as outsiders, gain their members’ trust, and then write about these people. If you spend longer periods of time in any group of human beings, you always learn some secrets that should remain secret. Institutional Review Boards are not well equipped to protect the anthropologist’s subjects against breaches of such secrecy. This largely remains a matter of the ethnographer’s ethos. If I feel unsure whether I can mention something, I usually ask people whether it would be okay or show them what I wrote. I was often surprised when people had no problems at all with what had seemed a spicy issue to me, but reacted quite sensitively to things which had seemed rather innocuous to me, for example, if they felt that I had overinterpreted the findings of their latest article.

In the history of science, the experimentalist has always had a greater authority than the fieldworker. How do you see the authority of the anthropologist in the psychedelic sciences?

The anthropologist’s authority is based on experience. And on the time it costs to conduct long-term fieldwork, to cultivate personal relations. But I don’t think that such ethnographic authority carries over into clinical and pharmacological research, if that’s what you mean by psychedelic sciences. I have been trying to get psychopharmacologists to think more seriously about supplementing placebo-controlled trials by culture-controlled trials or other methodologies that take into consideration set and setting. But it’s almost impossible to change a field from the outside and, at the end of the day, anthropologists who don’t go native remain outsiders.

Do you see conflicts between the projects of anthropologists and scientists in this field?

My project is different from but not antagonistic to the projects of the scientists I’ve been working with. If you look at what they publish and at what I publish, these writings are not alike without being incommensurable. We even share a lot of questions. These are not necessarily the questions that psychopharmacologists answer through their experiments and journal article publications, but they are questions psychedelic researchers discuss over lunch and afterhours.

This convergence of interests has to do with the fact that my anthropological work is not primarily ethnographic. I was interested in the psychedelic experience, in what these drugs are doing to humans and what humans are doing with these drugs. Writing about people – which is what ethnography means – was a necessary part of working through these questions. Because it is people who have these ideas, it is people who use these drugs in particular ways. But my ultimate aim is a more philosophical one. I’m trying to understand what psychedelic experiences are to human beings, how we come to have them and why we value them.

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Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective

Abstract

BACKGROUND:

Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group.

METHODS:

WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions.

RESULTS:

Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired.

CONCLUSION:

The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more complex cognitive measures in diverse ‘user categories’ using a combination of genetics, imaging techniques and neuropsychological assessments.

Kuypers, K. P., Theunissen, E. L., van Wel, J. H., Perna, E. B. D. S. F., Linssen, A., Sambeth, A., … & Ramaekers, J. G. (2016). Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective. PloS one, 11(2), e0149438. http://dx.doi.org/10.1371/journal.pone.0149438

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Effects of 3,4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting

Abstract

The drug 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”, “molly”) is a widely used illicit drug and experimental adjunct to psychotherapy. MDMA has unusual, poorly understood socioemotional effects, including feelings of interpersonal closeness and sociability. To better understand these effects, we conducted a small (n=12) within-subjects double-blind placebo controlled study of the effects of 1.5 mg/kg oral MDMA on social emotions and autobiographical disclosure in a controlled setting. MDMA displayed both sedative- and stimulant-like effects, including increased self-report anxiety. At the same time, MDMA positively altered evaluation of the self (i.e. increasing feelings of authenticity) while decreasing concerns about negative evaluation by others (i.e. decreasing social anxiety). Consistent with these feelings, MDMA increased how comfortable participants felt describing emotional memories. Overall, MDMA produced a prosocial syndrome that seemed to facilitate emotional disclosure and that appears consistent with the suggestion that it represents a novel pharmacological class.

Baggott, M. J., Coyle, J. R., Siegrist, J. D., Garrison, K. J., Galloway, G. P., & Mendelson, J. E. (2016). Effects of 3, 4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting. Journal of psychopharmacology (Oxford, England). dx.doi.org/10.1177/0269881115626348

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Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans.

Abstract

Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A.

Johnson, M. W., MacLean, K. A., Caspers, M. J., Prisinzano, T. E., & Griffiths, R. R. (2016). Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans. Journal of psychopharmacology (Oxford, England). http://dx.doi.org/10.1177/0269881116629125

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From mice to men: can ketamine enhance resilience to stress?

Abstract

The rapid antidepressant properties of intravenous ketamine have ignited high hopes from researchers, clinicians, and patients alike. While bottom-up patient demand has led some clinicians to offer repeated ketamine infusions directly to patients, academic commentators have warned against premature clinical adoption (1), at times likening the field’s enthusiasm to the misguided use of stimulants or opiates to induce short-term depression relief. The rapidity of ketamine’s antidepressant onset (2-hours post-infusion) is impressive, but effects dissipate almost as rapidly (3-7 days).

Price, R. B. (2016). From mice to men: can ketamine enhance resilience to stress?. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2016.02.011
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Naltrexone but not ketanserin antagonizes the subjective, cardiovascular and neuroendocrine effects of salvinorin-A in humans

Abstract

Background: Salvinorin-A is a terpene found in the leaves of the plant Salvia divinorum. When administered to humans, salvinorin-A induces an intense but short-lasting modified state of awareness, sharing features with those induced by the classical serotonin-2A (5-HT2A) receptor agonist psychedelics. However, unlike substances such as psilocybin or mescaline, salvinorin-A shows agonist activity at the kappa-opioid receptor (KOR) rather than at the 5-HT2A receptor. Here we assessed the involvement of KOR- and 5-HT2A-agonism in the subjective, cardiovascular, and neuroendocrine effects of salvinorin-A in humans.

Methods: We conducted a placebo-controlled, randomized, double-blind study with two groups of 12 healthy volunteers with experience with psychedelic drugs. There were four experimental sessions. In Group-1 participants received the following treatment combinations: placebo+placebo, placebo+salvinorin-A, naltrexone+placebo and naltrexone+salvinorin-A. Naltrexone, a nonspecific opioid receptor antagonist, was administered at a dose of 50 mg orally. In Group-2 participants received the treatment combinations: placebo+placebo, placebo+salvinorin-A, ketanserin+placebo and ketanserin+salvinorin-A. Ketanserin, a selective 5-HT2A antagonist, was administered at a dose of 40 mg orally.

Results: Inhalation of 1 mg of vaporized salvinorin-A led to maximum plasma concentrations at 1 and 2 minutes after dosing. When administered alone, salvinorin-A severely reduced external sensory perception and induced intense visual and auditory modifications, increased systolic blood pressure, and cortisol and prolactin release. These effects were effectively blocked by naltrexone, but not by ketanserin.

Conclusions: Results support kappa opioid receptor agonism as the mechanism of action underlying the subjective and physiological effects of salvinorin-A in humans, and rule out the involvement of a 5-HT2A-mediated mechanism.

Maqueda, A. E., Valle, M., Addy, P. H., Antonijoan, R. M., Puntes, M., Coimbra, J., … & Barker, S. (2016). Naltrexone but not ketanserin antagonizes the subjective, cardiovascular and neuroendocrine effects of salvinorin-A in humans. International Journal of Neuropsychopharmacology, pyw016. http://dx.doi.org/10.1093/ijnp/pyw016
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The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization

Abstract

Ayahuasca is an Amazonian psychoactive brew of two main components. Its active agents are β-carboline and tryptamine derivatives. As a sacrament, ayahuasca is still a central element of many healing ceremonies in the Amazon Basin and its ritual consumption has become common among the mestizo populations of South America. Ayahuasca use amongst the indigenous people of the Amazon is a form of traditional medicine and cultural psychiatry. During the last two decades, the substance has become increasingly known among both scientists and laymen, and currently its use is spreading all over in the Western world. In the present paper we describe the chief characteristics of ayahuasca, discuss important questions raised about its use, and provide an overview of the scientific research supporting its potential therapeutic benefits. A growing number of studies indicate that the psychotherapeutic potential of ayahuasca is based mostly on the strong serotonergic effects, whereas the sigma-1 receptor agonist effect of its active ingredient dimethyltryptamine raises the possibility that the ethnomedical observations on the diversity of treated conditions can be scientifically verified. Moreover, in the right therapeutic or ritual setting with proper preparation and mindset of the user, followed by subsequent integration of the experience, ayahuasca has proven effective in the treatment of substance dependence. This article has two important take-home messages: 1) the therapeutic effects of ayahuasca are best understood from a bio-psycho-socio-spiritual model, and 2) on the biological level ayahuasca may act against chronic low grade inflammation and oxidative stress via the sigma-1 receptor which can explain its widespread therapeutic indications.

Frecska, E., Bokor, P., & Winkelman, M. (2016). The therapeutic potentials of ayahuasca: possible effects against various diseases of civilization. Frontiers in Pharmacology, 7, 35. http://dx.doi.org/10.3389/fphar.2016.00035
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