OPEN Foundation

OPEN Foundation

Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain

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
Link to full text

EARS verslag van Simon Powell

ears508

Vorige maand organiseerde we in Amsterdam het European Ayahuasca Research Symposium. Simon Powell, auteur van het nieuwe boek The Psilocybin Solution, was erbij en schreef een uitgebreid verslag.

The Science of Ayahuasca—Gathering Momentum

I was recently fortunate enough to attend the European Ayahuasca Research Symposium. The academic event took place in the University of Amsterdam and was attended by about 200 people or so, mostly Dutch students as far as I could tell. My overall impression was that the science of ayahuasca is in its infancy and that more questions were raised by the content of the speakers’ talks than were answered. In other words, it seemed clear to me that the long revered psychological impact of ayahuasca, as with the impact of similar substances like psilocybin, is rife with research potential and that science has yet to really get to grips with the psychedelic visionary state. Science may know much about the various South American peoples who employ ayahuasca, it may know about its physical and chemical nature, it may even know which brain receptors are the principal site of its powerful neurological action, yet the bottom line is that we understand very little about consciousness itself and how consciousness can, with the right chemical intervention, expand into spectacular life‐changing visionary realms. Which implies that this ayahuasca symposium may well herald the start of a bigger research agenda to come.

The first speaker at the event was anthropologist Bia Labate who has studied ayahuasca use for over a decade and who recently wrote a book about ayahuasca and health. Labate explained how the ayahuasca phenomenon cuts across a dizzying array of scientific disciplines—psychology, psychiatry, psychotherapy, neuroscience, neurochemistry, anthropology, ethnobotany, phenomenology—you name it, ayahuasca touches upon all these fields of investigation. Not to mention religion and metaphysics of course which are modes of knowledge and enquiry also relevant to the ayahuasca experience. She went on to point out the various problems associated with conducting scientific research with ayahuasca—problems like its prohibition in most countries of the world along with the pejorative connotations inevitably associated with illegal drugs. And even in countries where ayahuasca is legal, this is generally only the case under the ritual auspices of a religious organisation such as the Santo Daime church. Given such widespread illegality, any scientific researcher out to seriously explore ayahuasca has a daunting task ahead of them. Labate also pointed out problematic issues such as the context (i.e. the setting) of the ayahuasca experience and the dosage used. Science requires a standardised methodology. Thus, if you want to investigate the healing efficacy of ayahuasca (and we should bear in mind that the therapeutic efficacy of psychedelics is very much in vogue at the current time), then it makes sense to standardise dose and setting as much as possible. With slightly uncomfortable candour, Labate went on to mention that in situ ayahuasca use is not always concerned with healing but may be about shamanic warfare.

Obviously it sounds more romantic to Western ears that ayahuasca is used primarily to heal the sick rather than to conjure up visionary poisonous darts to injure some enemy. Labate made it clear that the pop understanding of indigenous ayahuasca use is incomplete and that it is not all about dazzling healing visions but has a darker side. She also noted the conflicts that arise between the various kinds of logic involved in accounting for ayahuasca phenomenology—anything from the logic of psychiatry to shamanic logic. With so many ways and styles of describing what happens during a therapeutic ayahuasca session, which explanatory approach should science utilise?

The second speaker was Jorg Daumann. His particular take on the subject was clear right from the start. He kicked off by talking about the neurochemistry of schizophrenia and how psychedelics like DMT (the principal vision‐inducing ingredient of ayahuasca) could be used to understand the abhorrent neurochemistry associated with mental disease. I was rather surprised by this approach as I thought this kind of thinking had gone away in the early 1960s. With so much literature available on the spiritual and healing effects of substances like psilocybin, ayahuasca, and MDMA, is it really necessary to return to a conceptual approach that harks back to the work of Kraepilin (dating back over 100 years) that seeks similarities between entheogenesis and psychosis? The idea that psychedelics can mimic psychosis is a tad insulting to anyone who has partaken of them and experienced transcendental states of consciousness. Moreover, the gist of the entire symposium, or at least the most prominent thread, was that ayahuasca possesses valuable medicinal and therapeutic properties. So if Daumann’s approach is to be taken seriously then we would have to conclude that people under the influence of ayahuasca become temporarily psychotic in order to get well. That sounds like a contradiction to me, especially when one considers the tutorial nature of ayahuasca visions widely reported by Western users. Anyhow, Daumann was interested in the attention disorders that manifest in schizophrenia and how drugs like DMT (and ketamine) can elicit similarly degraded attention in certain experimental situations. The idea was that, under the influence of psychedelics, the filters of the human brain/mind do not function properly and therefore attention is less focused and more prone to be caught up in ostensibly trivial environmental information. In other words, attention gets focused in alternative ways and, according to Daumann, this mimics what happens in schizophrenia. Whilst it is undoubtedly true that psychedelics like DMT and psilocybin alter consciousness in oft curious and strange ways that may mimic in some way the strangeness associated with a psychotic mind, all this really demonstrates is that in both cases—in both schizophrenia and entheogenesis—large scale changes are occurring at the most complex and ‘higher end’ aspects of consciousness. With both psychosis and the psychedelic experience, the very core of what it is to be a consciously minded human being is modified and altered from the norm. As is the core of one’s relationship with culture, the environment and the rest of the reality process. So the most likely reason scientists first opted for the ‘psychotomimetic’ approach to psychedelics is because of the sheer unusualness of psychedelic consciousness compared to normal consciousness and not because psychedelics drive you mad. Having said as much, certainly it is the case that ‘bad trips’ can seem to the experiencer to be a kind of temporary madness. But I suspect similarities like this are minimal and are simply the result of complex psychological restructuring processes. In any case, the real question is whether Daumann’s approach helps us get to grips with something as strange as the DMT experience. As it was, Daumann concluded that the effects of ketamine upon attention seemed to be more closely related to the attention deficits found in psychosis than were the effects of DMT.

Brian Anderson was up next and he talked about ayahuasca’s role in psychiatry and he again brought up the psychotomimetic approach to the ayahuasca experience as opposed to the therapeutic approach. Does ayahuasca lead to a “harmful break with reality”? If so, then how to account for the growing number of popular testimonies concerning the curative visions that ayahuasca can potentiate? Anderson asked if some kind of biochemical change was the chief causal healing factor or was it the psychological nature of the visions themselves that caused the healing? As I intimated at the outset, ayahuasca raises many questions that pertain to consciousness, mind and body. Given that we have yet to really define what consciousness is and the relationship of the physical brain to the mind, is it any wonder that ayahuasca confounds science? Until we get some kind of handle on what the mind, or consciousness, is exactly and how it relates to the more familiar world of matter and energy, we will be hard pressed to get to grips with the kinds of transcendental consciousness potentiated by ayahuasca. In many ways, we are fumbling in the dark even though we may divine that something big and interesting is in our vicinity.

Anderson ended his discourse by mentioning a tentative ongoing study in which ayahuasca is being used to treat depression. Two subjects have apparently reported positive effects. Some audience questions at this point concerned what was new in the field of ayahuasca research. The two main items of interest appeared to be the growing interest in therapeutic studies along with more and more court cases concerning the legality of using ayahuasca. When you may have to go to court in order to keep your research study alive, it is not surprising that psychedelic science is so sluggish. This kind of socio‐political problem also raised the spectre of how religion is defined. Since most ayahuasca court cases seem to revolve around whether or not ayahuasca can be taken as part of a legitimate religious practice, the actual definition of a bona fide religion is called into question.

Anthropologist Rama Leclerc was next on stage and she talked about her studies of the Shipibo Konibo people of the Peruvian Amazon and the various kinds of person who visit them to partake in ayahuasca ceremonies. She went into a lot of detail about special diets and the relationship of the shaman with their apprentices. She also brought up the notion of plant spirits. She then made a comment that, although uttered rather casually, was actually quite loaded. Apparently there is a difference between (Western) males and females regarding the source of the healing/guiding force of ayahuasca, or the source of the Other as we can call it (i.e. the felt presence of an intelligence that one is in psychedelic communion with). According to Leclerc, males tend to interpret the guiding Other as something external to the self, whereas females tend to interpret it as something internal to the self. This implies that the common notion in psychedelic circles that the Other is some kind of entity separate from the self is but one interpretation of the ayahuasca experience, an interpretation that might be maleorientated and might only be popular because males tend towards more prominence in ayahuasca writings and such. I personally find this essentially hermeneutic issue (hermeneutics is the study of interpretation) of interest because it makes one question our assumptions about what the Other is. Undoubtedly psychedelics like DMT and psilocybin unleash visions that can seem to be tutorial and guiding, that have a life of their own, so much so that they may seem to be something separate from the self. But if this is simply an interpretation that comes in the wake of an extraordinary and unfamiliar state of consciousness, then it is equally plausible that what psychedelic plants do is to activate what can be referred to as a ‘higher aspect’ of the self, a kind of living inner wisdom if you will, a potential of the human mind to reorder itself and attain a more healthy and coherent state. So dramatic is this re‐ordering process that we may infer the process to be the work of an Other when, in fact, it is us, or at last a hitherto latent ‘higher’ potential of the human psyche.

Such speculation was actually affirmed by the following speaker, transpersonal psychologist Petra Bokor, who, in her studies of ayahuasca’s therapeutic effects in numerous Hungarian ceremonies, cited the “emergence of the higher self” as an indicator of therapeutic success. Bokor also noted that an important factor in the healing process was to integrate the ayahuasca experience via lifestyle changes and that this kind of process was equivalent to long term psychotherapy. This brought to mind the therapeutic role of ibogaine in treating drug addicts. A single visionary session with ibogaine (derived, like ayahuasca, from a shamanic plant) can be so powerful as to break a drug habit that, with traditional treatments, might take months or even years to cure. The extreme power of ayahuasca probably explains why many psychotherapists baulk at the very thought of utilising shamanic plants. The effects are so profound and so little understood, that it may be deemed safer to practice with more traditional medicines and therapy regimens.

Last to speak was psychologist Janine Schmid who, to her credit, managed to complete a study of ayahuasca self‐therapy in fifteen European subjects. This self‐therapy with the shamanic brew took various forms—such as visits to Peru, DIY ceremonies, involvement with the Santo Daime church, and so on. All the subjects suffered various ailments, mainly physical such as pain, tumours, depression, etc. Most felt better after their ayahuasca sessions—remissions were reported along with a decline in symptoms, even an apparently complete recovery. This kind of astonishing result—particularly physical healing as opposed to just feeling mentally better—clearly demands further study. If verified, ayahuasca might prove to be a medicine more powerful than we realise.

So what are to conclude from this tentative ayahuasca symposium? It seems to me that, as with similar psychedelics like psilocybin, the ayahuasca experience—so radically different to our normal frames of mind—is bursting with potential scientific research opportunities. In fact, given the eclectic array of disciplines involved that I alluded to at the outset, I can well envisage a multi‐disciplinary journal dedicated solely to ayahuasca. After all, we find journals dedicated solely to phenomena like cell biology, fluid mechanics, neurons, and obesity. What warrants any given dedicated journal is a subject rife with import and potential knowledge. And what can be more profoundly rife with potential knowledge than ayahuasca? In any case, if vigorously controlled ayahuasca experimentation is ever to begin in earnest, then precise dosages of its active ingredients would need to be available. Is this possible? I asked pharmacology professor Dave Nichols about this, as he has synthesized all manner of psychedelic drugs for official research purposes. He told me: “Certainly I think it would be possible to make capsules with variations in amounts of DMT and the various harmala alkaloids and have them evaluated by ayahuasca drinkers as to their efficacy. Then, use that as a ‘standardized’ formulation for clinical studies. I think it might even be possible for someone (probably in another country) to do a study like that with the pure alkaloids and publish it somewhere, then those data could be used to propose a study in the U.S. with that same formulation.”

So, the gauntlet has been laid down. There is a definite way ahead for science to explore ayahuasca’s widely attested healing potential. Do the groundwork in Europe (where restrictions may be easier to surmount) and then eventually extend the research into the USA. What may become of such a radical science agenda? If, that is, ayahuasca’s healing efficacy and safety were clearly ascertained and endorsed? Might we see therapy centres dotted about the globe, places where one could go to find a kind of healing not available elsewhere? Centres to refresh and revitalize the spirit and potentiate one’s ‘higher self’. Perhaps the real question is why ever not?

Simon G. Powell is the author of the The Psilocybin Solution which has just been published by Park Street Press. He would like to thank Bill Linton for supporting the creation of this piece.

EARS report by Simon Powell

Last month in Amsterdam we held the European Ayahuasca Research Symposium, a one-day lecture series exploring the current state of research into the medical, therapeutic, and spiritual uses of ayahuasca. Simon Powell, author of the recentely released The Psilocybin Solution, attended and wrote this thorough review.

The Science of Ayahuasca—Gathering Momentum

I was recently fortunate enough to attend the European Ayahuasca Research Symposium. The academic event took place in the University of Amsterdam and was attended by about 200 people or so, mostly Dutch students as far as I could tell. My overall impression was that the science of ayahuasca is in its infancy and that more questions were raised by the content of the speakers’ talks than were answered. In other words, it seemed clear to me that the long revered psychological impact of ayahuasca, as with the impact of similar substances like psilocybin, is rife with research potential and that science has yet to really get to grips with the psychedelic visionary state. Science may know much about the various South American peoples who employ ayahuasca, it may know about its physical and chemical nature, it may even know which brain receptors are the principal site of its powerful neurological action, yet the bottom line is that we understand very little about consciousness itself and how consciousness can, with the right chemical intervention, expand into spectacular life‐changing visionary realms. Which implies that this ayahuasca symposium may well herald the start of a bigger research agenda to come.

The first speaker at the event was anthropologist Bia Labate who has studied ayahuasca use for over a decade and who recently wrote a book about ayahuasca and health. Labate explained how the ayahuasca phenomenon cuts across a dizzying array of scientific disciplines—psychology, psychiatry, psychotherapy, neuroscience, neurochemistry, anthropology, ethnobotany, phenomenology—you name it, ayahuasca touches upon all these fields of investigation. Not to mention religion and metaphysics of course which are modes of knowledge and enquiry also relevant to the ayahuasca experience. She went on to point out the various problems associated with conducting scientific research with ayahuasca—problems like its prohibition in most countries of the world along with the pejorative connotations inevitably associated with illegal drugs. And even in countries where ayahuasca is legal, this is generally only the case under the ritual auspices of a religious organisation such as the Santo Daime church. Given such widespread illegality, any scientific researcher out to seriously explore ayahuasca has a daunting task ahead of them. Labate also pointed out problematic issues such as the context (i.e. the setting) of the ayahuasca experience and the dosage used. Science requires a standardised methodology. Thus, if you want to investigate the healing efficacy of ayahuasca (and we should bear in mind that the therapeutic efficacy of psychedelics is very much in vogue at the current time), then it makes sense to standardise dose and setting as much as possible. With slightly uncomfortable candour, Labate went on to mention that in situ ayahuasca use is not always concerned with healing but may be about shamanic warfare.

Obviously it sounds more romantic to Western ears that ayahuasca is used primarily to heal the sick rather than to conjure up visionary poisonous darts to injure some enemy. Labate made it clear that the pop understanding of indigenous ayahuasca use is incomplete and that it is not all about dazzling healing visions but has a darker side. She also noted the conflicts that arise between the various kinds of logic involved in accounting for ayahuasca phenomenology—anything from the logic of psychiatry to shamanic logic. With so many ways and styles of describing what happens during a therapeutic ayahuasca session, which explanatory approach should science utilise?

The second speaker was Jorg Daumann. His particular take on the subject was clear right from the start. He kicked off by talking about the neurochemistry of schizophrenia and how psychedelics like DMT (the principal vision‐inducing ingredient of ayahuasca) could be used to understand the abhorrent neurochemistry associated with mental disease. I was rather surprised by this approach as I thought this kind of thinking had gone away in the early 1960s. With so much literature available on the spiritual and healing effects of substances like psilocybin, ayahuasca, and MDMA, is it really necessary to return to a conceptual approach that harks back to the work of Kraepilin (dating back over 100 years) that seeks similarities between entheogenesis and psychosis? The idea that psychedelics can mimic psychosis is a tad insulting to anyone who has partaken of them and experienced transcendental states of consciousness. Moreover, the gist of the entire symposium, or at least the most prominent thread, was that ayahuasca possesses valuable medicinal and therapeutic properties. So if Daumann’s approach is to be taken seriously then we would have to conclude that people under the influence of ayahuasca become temporarily psychotic in order to get well. That sounds like a contradiction to me, especially when one considers the tutorial nature of ayahuasca visions widely reported by Western users. Anyhow, Daumann was interested in the attention disorders that manifest in schizophrenia and how drugs like DMT (and ketamine) can elicit similarly degraded attention in certain experimental situations. The idea was that, under the influence of psychedelics, the filters of the human brain/mind do not function properly and therefore attention is less focused and more prone to be caught up in ostensibly trivial environmental information. In other words, attention gets focused in alternative ways and, according to Daumann, this mimics what happens in schizophrenia. Whilst it is undoubtedly true that psychedelics like DMT and psilocybin alter consciousness in oft curious and strange ways that may mimic in some way the strangeness associated with a psychotic mind, all this really demonstrates is that in both cases—in both schizophrenia and entheogenesis—large scale changes are occurring at the most complex and ‘higher end’ aspects of consciousness. With both psychosis and the psychedelic experience, the very core of what it is to be a consciously minded human being is modified and altered from the norm. As is the core of one’s relationship with culture, the environment and the rest of the reality process. So the most likely reason scientists first opted for the ‘psychotomimetic’ approach to psychedelics is because of the sheer unusualness of psychedelic consciousness compared to normal consciousness and not because psychedelics drive you mad. Having said as much, certainly it is the case that ‘bad trips’ can seem to the experiencer to be a kind of temporary madness. But I suspect similarities like this are minimal and are simply the result of complex psychological restructuring processes. In any case, the real question is whether Daumann’s approach helps us get to grips with something as strange as the DMT experience. As it was, Daumann concluded that the effects of ketamine upon attention seemed to be more closely related to the attention deficits found in psychosis than were the effects of DMT.

Brian Anderson was up next and he talked about ayahuasca’s role in psychiatry and he again brought up the psychotomimetic approach to the ayahuasca experience as opposed to the therapeutic approach. Does ayahuasca lead to a “harmful break with reality”? If so, then how to account for the growing number of popular testimonies concerning the curative visions that ayahuasca can potentiate? Anderson asked if some kind of biochemical change was the chief causal healing factor or was it the psychological nature of the visions themselves that caused the healing? As I intimated at the outset, ayahuasca raises many questions that pertain to consciousness, mind and body. Given that we have yet to really define what consciousness is and the relationship of the physical brain to the mind, is it any wonder that ayahuasca confounds science? Until we get some kind of handle on what the mind, or consciousness, is exactly and how it relates to the more familiar world of matter and energy, we will be hard pressed to get to grips with the kinds of transcendental consciousness potentiated by ayahuasca. In many ways, we are fumbling in the dark even though we may divine that something big and interesting is in our vicinity.

Anderson ended his discourse by mentioning a tentative ongoing study in which ayahuasca is being used to treat depression. Two subjects have apparently reported positive effects. Some audience questions at this point concerned what was new in the field of ayahuasca research. The two main items of interest appeared to be the growing interest in therapeutic studies along with more and more court cases concerning the legality of using ayahuasca. When you may have to go to court in order to keep your research study alive, it is not surprising that psychedelic science is so sluggish. This kind of socio‐political problem also raised the spectre of how religion is defined. Since most ayahuasca court cases seem to revolve around whether or not ayahuasca can be taken as part of a legitimate religious practice, the actual definition of a bona fide religion is called into question.

Anthropologist Rama Leclerc was next on stage and she talked about her studies of the Shipibo Konibo people of the Peruvian Amazon and the various kinds of person who visit them to partake in ayahuasca ceremonies. She went into a lot of detail about special diets and the relationship of the shaman with their apprentices. She also brought up the notion of plant spirits. She then made a comment that, although uttered rather casually, was actually quite loaded. Apparently there is a difference between (Western) males and females regarding the source of the healing/guiding force of ayahuasca, or the source of the Other as we can call it (i.e. the felt presence of an intelligence that one is in psychedelic communion with). According to Leclerc, males tend to interpret the guiding Other as something external to the self, whereas females tend to interpret it as something internal to the self. This implies that the common notion in psychedelic circles that the Other is some kind of entity separate from the self is but one interpretation of the ayahuasca experience, an interpretation that might be maleorientated and might only be popular because males tend towards more prominence in ayahuasca writings and such. I personally find this essentially hermeneutic issue (hermeneutics is the study of interpretation) of interest because it makes one question our assumptions about what the Other is. Undoubtedly psychedelics like DMT and psilocybin unleash visions that can seem to be tutorial and guiding, that have a life of their own, so much so that they may seem to be something separate from the self. But if this is simply an interpretation that comes in the wake of an extraordinary and unfamiliar state of consciousness, then it is equally plausible that what psychedelic plants do is to activate what can be referred to as a ‘higher aspect’ of the self, a kind of living inner wisdom if you will, a potential of the human mind to reorder itself and attain a more healthy and coherent state. So dramatic is this re‐ordering process that we may infer the process to be the work of an Other when, in fact, it is us, or at last a hitherto latent ‘higher’ potential of the human psyche.

Such speculation was actually affirmed by the following speaker, transpersonal psychologist Petra Bokor, who, in her studies of ayahuasca’s therapeutic effects in numerous Hungarian ceremonies, cited the “emergence of the higher self” as an indicator of therapeutic success. Bokor also noted that an important factor in the healing process was to integrate the ayahuasca experience via lifestyle changes and that this kind of process was equivalent to long term psychotherapy. This brought to mind the therapeutic role of ibogaine in treating drug addicts. A single visionary session with ibogaine (derived, like ayahuasca, from a shamanic plant) can be so powerful as to break a drug habit that, with traditional treatments, might take months or even years to cure. The extreme power of ayahuasca probably explains why many psychotherapists baulk at the very thought of utilising shamanic plants. The effects are so profound and so little understood, that it may be deemed safer to practice with more traditional medicines and therapy regimens.

Last to speak was psychologist Janine Schmid who, to her credit, managed to complete a study of ayahuasca self‐therapy in fifteen European subjects. This self‐therapy with the shamanic brew took various forms—such as visits to Peru, DIY ceremonies, involvement with the Santo Daime church, and so on. All the subjects suffered various ailments, mainly physical such as pain, tumours, depression, etc. Most felt better after their ayahuasca sessions—remissions were reported along with a decline in symptoms, even an apparently complete recovery. This kind of astonishing result—particularly physical healing as opposed to just feeling mentally better—clearly demands further study. If verified, ayahuasca might prove to be a medicine more powerful than we realise.

So what are to conclude from this tentative ayahuasca symposium? It seems to me that, as with similar psychedelics like psilocybin, the ayahuasca experience—so radically different to our normal frames of mind—is bursting with potential scientific research opportunities. In fact, given the eclectic array of disciplines involved that I alluded to at the outset, I can well envisage a multi‐disciplinary journal dedicated solely to ayahuasca. After all, we find journals dedicated solely to phenomena like cell biology, fluid mechanics, neurons, and obesity. What warrants any given dedicated journal is a subject rife with import and potential knowledge. And what can be more profoundly rife with potential knowledge than ayahuasca? In any case, if vigorously controlled ayahuasca experimentation is ever to begin in earnest, then precise dosages of its active ingredients would need to be available. Is this possible? I asked pharmacology professor Dave Nichols about this, as he has synthesized all manner of psychedelic drugs for official research purposes. He told me: “Certainly I think it would be possible to make capsules with variations in amounts of DMT and the various harmala alkaloids and have them evaluated by ayahuasca drinkers as to their efficacy. Then, use that as a ‘standardized’ formulation for clinical studies. I think it might even be possible for someone (probably in another country) to do a study like that with the pure alkaloids and publish it somewhere, then those data could be used to propose a study in the U.S. with that same formulation.”

So, the gauntlet has been laid down. There is a definite way ahead for science to explore ayahuasca’s widely attested healing potential. Do the groundwork in Europe (where restrictions may be easier to surmount) and then eventually extend the research into the USA. What may become of such a radical science agenda? If, that is, ayahuasca’s healing efficacy and safety were clearly ascertained and endorsed? Might we see therapy centres dotted about the globe, places where one could go to find a kind of healing not available elsewhere? Centres to refresh and revitalize the spirit and potentiate one’s ‘higher self’. Perhaps the real question is why ever not?

Simon G. Powell is the author of the The Psilocybin Solution which has just been published by Park Street Press. He would like to thank Bill Linton for supporting the creation of this piece.

Brian Anderson – Ayahuasca in psychiatry: From psiquiatría folklórica to neuroimaging

This presentation analyzes from an anthropological perspective some of the ways that ayahuasca’s curative potentials have been portrayed in conventional psychiatry from the 1950s until today. Through considering seldom-cited and difficult-to-access publications and other forms of academic psychiatric productions, it is shown how different cultures within psychiatry have shaped the construction of scientific ‘facts’ of how ayahuasca can affect and heal the mind. Suggestions are made for how such a historical and cultural analysis of psychiatric discourse can be applied to the development of the contemporary ethnopsychiatric study of ayahuasca.

Rama Leclerc – The bridge of knowledge: Special links between Shipibo curanderismo and Westerner practices with ayahuasca

The Shipibo-Konibo people from the Peruvian Amazon are part of the Pano ethnolinguistic family. Distributed within more than one hundred villages, the inhabitants live along the Ucayali River and its tributaries, on both sides of Pucallpa city. The Shipibo women are recognized for their handicrafts (especially pottery and textiles) decorated with magnificent geometrical drawings. The curandero sees these same patterns in his visions during the night-sessions of ayahuasca. The curandero is a practitioner, a shaman who thanks to his initiatory apprenticeship, has developed the capacity to make the link between the human beings in the physical world and the spirits in the world above. These spirits are endowed with volition and intentionality just like human consciousness. Moreover, they can find embodiment in an animal, plant, mineral or even in a geographical structure. The knowledge of the curandero is based on the incorporation of powerful plants called rao. The strength of these rao is linked to their double nature: a material aspect, the physicality or the body of the plant, juxtaposed to the spiritual aspect, the interiority or the spirit of the plant. After ingestion, these plants pass on some knowledge to the curandero during dreams or visions. He will learn to understand and to use them according to his progress along his initiatory route. After the initiation diet, he can see his recently acquired powers through the ingestion of the ayahuasca decoction.

For several years, and this movement accelerates, a greater number of Westerners visit repeatedly Shipibo curanderos in their small villages. They come from diverse horizons and their reasons are varied: a disease, a need for exoticism, a mystic quest, etc. By studying this growing tendency, we can observe a reappropriation of the speech of the other like a kind of knowledge crossing. Shipibo curanderos get better organized in order to welcome better these people in a more adapted way to their culture; whereas, in Europe, the followers of ayahuasca recreate a small community, developing a kind of subculture that integrates this non-native practice into particular processes of therapies. Making a link between both continents, I am interested to analyze elements absorbed, incorporated, and even thrown back in these new syncretic therapy practices as well as the transformation of the Shipibo curanderos’ speech. Moreover, I will approach other interesting peculiarities to understand better the functioning of the Shipibo shamanism; such as consubstantiation, the finished conception of the self-contained universe, the notion of niwe (energy), olfactory perception as a particular hermeneutic, etc.

Petra Bokor – Integration process and possible therapeutic effects of ayahuasca in non-therapeutic setting

The presentation starts with an overview of the research on the psychotherapeutic effects of ayahuasca and presents in details an investigation into the integration process of ayahuasca experiences. Eleven individuals participating in a series of ayahuasca rituals were followed for the period of one year in a study carried out in Hungary. A core theme was identified from each participant’s intentions and emerging psychological issues and the changes on such themes were tracked during both the participants’ ayahuasca experiences and their day-to-day lives. A methodology aiming to assess therapeutic change was used for the analysis, dividing the therapeutic process into seven phases from problem definition to termination. By the end of the research, almost all participants attained and began to practice a new behaviour pattern to their problems, all of them at varying levels and pace. Participants provided rich subjective reports involving remarkable breakthroughs as well as crises. Another Hungarian study carried out by Dr. Ede Frecska, aiming to investigate ayahuasca’s effects on creativity, will also be touched upon.

Janine Schmid – Self-therapy with ayahuasca

The often-used term ‘healing ritual’ for nearly all kinds of ayahuasca rituals (Santo Daime rituals, neo-shamanistic rituals, and even do-it-yourself-rituals) attracts people searching for an alternative method for treatment. In this study, fifteen people with first-hand experience with ayahuasca ‘therapy’ for a special disease (like chronic pain, cancer or tumours, asthma or allergic reaction to food, depression, alcohol abuse, Hepatitis C, tinnitus, glaucoma) were interviewed twice about their ideas and beliefs on ayahuasca and healing, and about their subjective theories on the etiology of disease and change. In most cases, people were convinced their illness was influenced in a positive way by ayahuasca. ‘Healing’ is not limited to the cure of physical and mental diseases but extends to a lot of psychological and even spiritual problems. Often ‘ self-transformation’ and ‘self-healing’ went hand-in-hand.

Although ayahuasca was an important help for all people coping with illness and self-actualization, it is clearly not a ‘universal remedy’ which provides healing for free – it involves a lot of personal work to succeed. Therefore there must be a critical discussion of some healing concepts and their implications. An idea commonly found – not only in the field of ayahuasca users – was that so-called ‘positive and negative thinking’ can influence the course of a disease. Likewise, ancient wisdom (“millennial indigenous knowledge”) was taken for granted and often used for legitimation and to deny negative effects or difficulties. These and other problematic issues will be questioned and discussed.

Jörg Daumann – Pharmacological modulation of attentional processes in the DMT and ketamine model of psychosis

Deficits in attentional functions are counted among the core cognitive symptoms in schizophrenic patients. Pharmacologic challenges with hallucinogens have been used as models for psychosis. In this talk, I give an overview of our studies on the pharmacological modulation of DMT and ketamine on different aspects of attentional functions. We investigated prepulse inhibition of the startle reflex (PPI), mismatch negativity (MMN), and visual and auditory alertness as well as spatial orienting of attention combined with fMRI. Data of fifteen healthy subjects were collected in randomized, double-blind, crossover studies. Ketamine increased PPI, whereas DMT had no significant effects on PPI. Ketamine decreased and DMT tended to decrease startle magnitude. Furthermore, we found blunted MMN after both drugs. However, the reduction in MMN activity was overall more pronounced after ketamine intake, and only ketamine had a significant impact on the frontal source of MMN. Administration of DMT and ketamine led to different cortical activations during the performance of both tasks. The ketamine model and the DMT model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis.

Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects

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

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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30 April - Q&A with Rick Strassman

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