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[Boekrecensie] Entheogens, Society & Law: Towards a Politics of Consciousness, Autonomy & Responsibility

41U01VD7AyL._SX340_BO1,204,203,200_Entheogens, Society & Law: Towards a Politics of Consciousness, Autonomy & Responsibility by Daniel Waterman, edited by Casey William Hardison, Melrose Books, 2013.

Psychoactieve middelen zijn sterk verstrengeld met de samenleving. Ze veroorzaken uiterst subjectieve effecten, en zijn tegelijk zeer politiek geladen. Daarnaast bepaalt de culturele en maatschappelijke context grotendeels ook de inhoud en interpretatie van de psychedelische ervaring. ‘Entheogens, Society & Law’, geschreven door Daniel Waterman, handelt over deze wisselwerking. In zijn boek bespreekt Waterman de verwevenheid van bewustzijn en ethiek, en voert hij aan dat een herziening van wettelijke keuzes nodig is om te komen tot een geschiktere manier om met deze middelen om te gaan. Het is een boek met een brede kijk over een hele waaier aan onderwerpen.

Na een korte persoonlijke inleiding toont Waterman hoe de manier waarop we over psychoactieve stoffen praten niet enkel de ervaring ermee beïnvloedt, maar ook de interpretatie en de al dan niet gunstige afloop hiervan. Op dezelfde manier stelt hij dat wetgeving dergelijke overtuigingen die we aanhouden over psychoactieve middelen vormgeeft, en dat dit dan weer het beeld bepaalt dat we van die middelen en ook van onszelf hebben.

Het tweede hoofdstuk weidt uit over de verschillende concepten die doorheen de geschiedenis over psychoactieve stoffen werden gevormd, en over de uitkomsten van deze conceptvormingen. Drugs en druggebruikers hebben vele gezichten, en Waterman brengt een zorgvuldige analyse van al de verschillende rollen die ze in de samenleving invullen, zowel positieve als negatieve. Hij toont de complexiteit van deze concepten, en de vele verschillende mogelijke interpretaties ervan. Een dergelijke analyse draagt bij tot een beter inzicht in psychedelica en in de psychedelische ervaring, en werd voordien nergens anders zo uitgebreid gepubliceerd.

In het derde hoofdstuk vinden we een omvangrijk stuk over het werk van Prof. Jan Bastiaans, een Nederlandse psychiater die mensen die leden aan wat toen werd aangeduid als het ‘concentratiekampsyndroom’ behandelde met LSD. Dit concentratiekampsyndroom zou later worden ingedeeld in de recentere categorie PTSS (posttraumatisch stresssyndroom). Bastiaans werd opgeleid in de klassieke psychoanalyse, en paste deze technieken later toe in de context van psychedelische therapie. Aan het einde van de jaren 1980 kwam Bastiaans onder vuur te liggen omdat hij geen degelijk archief had aangelegd, wat een evaluatie van de doeltreffendheid van zijn behandeling onmogelijk maakte. Hoewel dit gedeelte in belangrijke mate gebaseerd is op het werk van Stephen Snelders en op de biografie door Bram Enning, biedt dit boek als een van de eerste in het Engels een uitgebreid overzicht van het werk van Bastiaans, en is het een welkome toevoeging aan de historische studie van psychedelisch onderzoek.

In het volgende deel handelt het boek over de transpersonele psychologie van Stanislav Grof. Ondanks het feit dat Grof op dit gebied een topfiguur is, wordt hij zelden vergeleken met zijn voorgangers, zoals Sigmund Freud en zijn erfgenamen Carl Jung, Otto Rank en Wilhelm Reich, of met tijdgenoten zoals Abraham Maslow. Deze vergelijking plaatst Grof in een afstammingslijn van psychoanalysten, en hierdoor zien we hoe hij van deze traditie leerde, maar ook hoe hij ze uitbreidde door intensief met LSD te werken, zowel in de Tsjechische Republiek als in de VS.

In zijn laatste hoofdstuk toont de auteur hoe de transpersonele ervaring centraal staat in een waaier aan religies, en betoogt hij dat deze ervaringen mensen in staat stellen te integreren op persoonlijk en sociaal vlak. In die zin, voert Waterman aan, vormen zij een toonbeeld van ethiek, omdat ze van ons vereisen dat we in brede zin verantwoordelijkheid nemen voor onze daden. Omgekeerd belet het verbieden van zulke ervaringen (of althans van sommige manieren om ze te veroorzaken) mensen om bewuster, en bijgevolg mededogender en aardiger te worden.

Het boek is niet neutraal, en pretendeert dit ook niet te zijn. Zowel de auteur als de uitgever zijn uitgesproken voorstanders van cognitieve vrijheid en vrijheid van bewustzijnsverruiming. Toch zijn hun beweringen ondersteund door relevant onderzoek, en vindt hun politieke stellingname haar wortels in een sterke traditie van wetenschappelijk onderzoek en filosofisch denken, hoewel conservatieven ze als radicaal zouden kunnen bestempelen.

Het boek heeft wel zijn gebreken, waarvan het belangrijkste is dat het vaak onduidelijk is waar de argumentatie de lezer naartoe wil brengen. Omdat vele onderwerpen uitgebreid worden behandeld verliest men gemakkelijk de draad van de redenering. Een verdere uitwerking van de manier waarop uitweidingen passen binnen het algemene betoog zou er een strakker boek van hebben gemaakt. In deze vorm lijken de onderwerpen, hoe boeiend ook op zichzelf, vaak los te staan van elkaar. Bijgevolg moet de lezer zelf de samenhang van het betoog zien op te bouwen, wat het lezen van het boek soms veeleisend maakt, en een stevige concentratie van de lezer vereist.

Een ander gebrek is dat sommige ideeën zowel in de voetnoten als in de hoofdtekst worden uitgelegd. Deze overbodige herhalingen, alsook sommige fouten en slordigheden in de voetnoten, ontsieren een tekst die overigens degelijk geannoteerd is. Deze beide punten hadden tijdens de redactionele bewerking opgelost moeten worden.

Er zijn echter parels genoeg te vinden in het geheel. Dit boek verruimt de blik ver voorbij de grenzen van wat gewoonlijk te vinden is in de literatuur over psychedelica. De auteur behandelt vele vraagstukken die meestal onaangeroerd blijven, en slaagt er ondanks alles in om het geheel aaneen te rijgen. Dit is een boek voor mensen die geïnteresseerd zijn in de wisselwerking tussen onze manier van denken over gewijzigde bewustzijnstoestanden en de middelen die deze veroorzaken, en in de invloed daarvan op de ervaring en de manier waarop deze terugkoppelingen bepalen hoe we als samenleving omgaan met deze stoffen.

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[Interview] Felix Hasler: “What’s missing is a holistic view on the psyche”

Felix_Hasler_Portrait_by_Oscar_Lebeck_(G&G)-cropAs a psychopharmacologist, Felix Hasler has studied the pharmacology of psilocybin over a decade together with Franz Vollenweider at the University of Zürich. A short time later he published his book “Neuromythology”, in which he argues against the current hype within the field of neuroscience and for a more moderate and humble scientific practice. Felix is also a member of the neuroculturelab, a multimedia project aiming to raise awareness of the modern view of the self that is suggested by brain researchers and is the subject of controversial discussion among philosophers. We met in Berlin, where he is currently a guest researcher at the Berlin School of Mind and Brain (Humboldt University), to talk about current tendencies within the neurosciences, mental disorders and the medical application of psychedelics.

Mental disorders are on the rise and research labs around the world are trying to improve pharmacological intervention, ranging from finding biomarkers for schizophrenia to genetic screening for depression. In your book “Neuromythology”, you express your doubts towards the successfulness of such biopsychiatric experiments. Can you shortly explain why?

The big buzzword we talk about here is the one of “personalised medicine”. It creates the impression that mental disorders could soon be treated on an individual basis. Treated pharmacologically, I should add, since psychoanalysis of course is traditionally a highly individualised way of dealing with mental problems. In the biomedical context of mental disorders, I think that “personalised medicine” is a big illusion. We still have no clue how depression emerges from the brain – if it does in the first place. Even in somatic medicine, personalised medicine works in only 2 cases to date. First, there is Herceptin, a chemostatic against certain types of breast cancer. It is known that tumour cells produce different levels of the protein onto which the drug binds. The higher this protein expression, the higher the efficacy of the drug. Secondly, some drugs can be prescribed “personally” when it is known whether the patient is a slow or fast metabolizer of the substance being prescribed. Thus overdosing can be avoided. But especially in psychiatry, the only remedies available today act highly unspecifically, e.g. antidepressants.

Is it the research methods that have to be improved in order to one day establish individualised treatment for mental disorders, or is it simply impossible to completely understand the aetiology of illnesses of such a complex system as the human brain?

If you look back in the history of psychiatry, there has always been discrimination between psychiatric and neurological disorders. Ones that could be treated with classic medical interventions (drugs, surgery, substitution, etc.) and ones that could not. Today, we have a more complex situation where this distinction is almost given up. At least in the academic discourse, everything is conflated in the umbrella term “neuropsychiatric disorders”. There certainly are examples of mental symptoms that can be explained on a neurological basis like Dementia with psychotic episodes or Chorea Huntington. However, with other affections such as depression or schizophrenia, the face of affairs seems to differ a whole lot. This leads me to believe that there won’t be any specific and truly successful drug treatments for mental disorders in the future. There is no such thing as a “depressive brain”. Therefore we don’t even know the target configuration of a “non-depressive brain” that we could reinstall by some kind of biomedical treatment. One reason for this is the immense physiological variability in human brains. The expression of, let’s say, a specific serotonin transporter that is discussed to be involved in depression fluctuates within several hundred per cent in large enough study populations. Ergo, it is very difficult to extract a general hypothesis on healthy or diseased brain physiology regarding depression. Focussing on single neurotransmitter systems such as serotonin and changing their functionality (eg. by SSRIs) has not shown to be very effective. Neurons don’t get depressed, only humans do. Mental disorders, in my view, are disorders of consciousness and therefore have to be treated on a much more holistic level, taking the whole human being into account. I’m aware that many biological psychiatrists say the same thing. But when you then look at the current clinical practice, this seems little more than lip service.

When you say that the prescription drugs against depression and schizophrenia don’t really have medical benefit for the patients, are the definitions and medical treatments of these disorders just a scam in order to sell more and more pharmaceuticals?

There are of course criteria to classify mental disorders in order to inform medical treatments. The process of these groupings, however, is not based on scientific grounds. The whole mental diagnostics are in fact decisions by members of the American Psychiatric Association (APA) who compile their results in the DSM, the Diagnostic and Statistical Manual for Mental Disorders. It is a pretty simple system of expert consensus that defines which psychological state is deemed a mental disorder and which one is not. From these rather arbitrary definitions arise fashionable complaints for people that objectively have no pathological significance. Someone who is by nature an introvert may thus be diagnosed with social anxiety and treated with SSRIs. That’s a classic case. On the other hand, some disorders become very rare in clinical practice – such as catatonic schizophrenia – or disappear entirely from the diagnostic manual, such as hysteria, which was very common in Sigmund Freud’s times. I would not go so far as to state that depression is another myth put out by “big pharma”, however it is interesting that more and more people are diagnosed with depression without clear evidence that there are indeed more depressed patients than decades ago…

…because naturally occurring melancholic phases that every one of us experiences from time to time are being pathologized?

Precisely! The pharmaceutical companies have an intrinsic interest in increasing the number of psychiatric patients – at least on paper – in order to sell their products. With the previously mentioned human-made definitions of mental disorders this is easily achievable. Their tool is the so-called “disease awareness campaign”. This happens in accordance with patient organisations and sponsored of course by the respective pharmaceutical industries themselves. The result of such a campaign is that a person hears that if they experience symptom abc, they should go see a doctor and check for disease xyz. They then become a patient that they actually aren’t and have to take medications that they do not need.

As well as I can retrace your line of argumentation, shouldn’t you as a neuropsychopharmacologist be in favour of such pharmaceutical developments? In 2006, at a symposium in honour of Albert Hofmann’s 100th birthday, you were still convinced that a more detailed analysis of the serotonergic neurotransmitter system would automatically lead to a better understanding of some mental disorders.

10 years ago I was indeed still convinced that there is something like a “neurochemical self”. By that I mean that conscious experiences and mental disorders can be explained in a reductionist way by investigating the neurobiological foundations of these mental states in a scientific way. Hallucinogens such as psilocybin are in that sense a perfect tool, as they pharmacologically act very specifically on certain serotonergic receptors and psychologically result in a very profound alteration of consciousness. I am still very much in favour of research into psychedelics because I believe that they possess a big potential for treatment in psychiatric institutions. However, I’m strongly convinced that neither the psychedelic experience nor mental disorders can be explained by mere alterations in brain chemistry. What’s missing is a holistic view on the psyche taking into consideration both the isolated brain and the whole person as a social and political being.

With what skills would you equip a future researcher who wishes to study the brain in the context of psychedelics and mental disorders so that they can pursue that goal of scientific holism?

I believe modesty is a rare characteristic that I wish to be cultivated more amongst young scientists. Especially in medical aspects of research there exists a tremendous misinterpretation in the mind of students thinking that science would always result in axiomatic theories that last forever. This is not the case at all! Everyone should take a class in the history of science to get an idea of which aspects of nature actually can be studied and which can’t. This is also important to get a feeling for the philosophical question of what can be known at all and to which degree study results may be interpreted in order for them to still be validated. An example of this are the EEG experiments performed in the 1920’s. Scientists were unequivocally clear about their claim that these visualised brain waves are the biological foundation to explain the phenomenon of consciousness. Or look at the study of phrenology in the 19th century. Advocates of this theory were convinced that they could identify criminals by measuring the shape of people’s skulls. Nowadays neuroscientists look for biological markers in the brain and in the genes that might predict criminal behaviour. Critics of this “predictive neuroscience” say that this is nothing but an updated form of phrenology. A critical attitude towards scientific claims is very important, especially in the neurosciences.

You have worked within this field yourself for 10 years at the ETH Zürich in the lab together with one of the pioneers in the second wave of psychedelic research, Franz Vollenweider. What was your motivation to do so?

On the one hand it was the fundamental research within the neuroscientific field that I found very interesting. On the other hand it was the scientific examination of human consciousness. Substances like psilocybin are tailor-made for that endeavour in that they display an ideal interface between biology and the soul, psyche or however you may want to call the mental aspect of the human experience. There is also the field of “experimental psychopathology” with psychedelics, but I’m sceptical about the epistemic and practical usefulness of the “model psychosis” paradigm. I am a strong supporter of investigating the medical properties of psychedelics, however I wonder if it is possible to extract objective scientific insights with hallucinogens given the subjective nature of a psychedelic experience. In Zürich I learned how extremely difficult it is to explain states of consciousness that emerge from substances like psilocybin by scientific means.

Do you think that this is even necessary? In the case of mind-altering drgalateaugs, isn’t it the subjective experience of the experience itself that initiates the healing process in a patient?

It depends on which substance we are talking about. With the application of MDMA I think the treatment should always have a depth psychological approach in order to reach the maximum effect – take the MDMA-assisted psychotherapy against posttraumatic stress disorder as an example. With ketamine against depression I am not sure whether a “full-blown” experience is necessary to evoke its medicinal properties. The answer to this question depends to a high degree on who you ask. A curandero in Peru who works with ayahuasca won’t care a lot about the pharmacological principle of DMT. It’s “mother Ayahuasca” who treats the soul of the patients. I like that idea because it fits into the holistic principle of healing I talked about. A bio-psychiatrist in the Western world, on the other hand, would probably be very much interested in the biochemical pathways that such a substance will create in order to synthesise analogues that can be sold as pharmaceuticals.

What is your opinion on psychedelic science in the future?

Everyone who has undergone a psychedelic experience first-hand would agree that substances like psilocybin and LSD are very potent and can be highly effective tools. Shortcuts to the depth of your soul – and possibly to the roots of your mental problems. But psychedelics are very sharp knives with which you can also cause a lot of harm if not handled correctly. With every experience, you start into an uncertain journey. That journey might turn into something beautiful, meaningful, eye-opening and even life-transforming, but you may also find yourself in the pit of a horror trip. Both the future of scientific research and the acceptance of psychedelic treatments in society will depend on how much the uncertainty in the outcome of a psychedelic experience can be controlled and steered. But again, there is so much variety in the psychedelic experience. And in biomedical research there is always the problem of the impact of a scientific clinical setting on the experience. In PET studies with psilocybin we did in Zürich, we saw that study subjects who managed to turn to their inner world had very positive experiences, whereas others who focussed on the outside world had quite a hard time given the anxiogenic sterile high-tech environment of a hospital PET centre. That was about 50:50. But how can you predict beforehand who will have what type of experience?

What is your advice to someone who would also want to engage in psychedelic science?

Unfortunately, I don’t think that there is a general plan or even an academic curriculum that you can follow. It depends a great deal on the political circumstances. Switzerland for instance is quite an ideal country to do psychedelic research, because politicians and healthcare officials there are not ideologists, but pragmatic bureaucrats. You can do research with almost any substance if your experimental design is sound, the study planned seriously and conducted in a strictly scientific way. Of course, ethics committees need to agree on your research plan and attest that your subjects won’t be at risk to be harmed. In that case, the Swiss government will not only tolerate your work but will also actively support it. In the US, of course, Rick Doblin from MAPS, a “man on a mission” advocating the medical use of psychedelics since the 1990s would be someone to talk to about research opportunities. One reason why research with LSD and other psychedelics might be easier in the future is because hallucinogen research “2.0” got completely depoliticised and doesn’t follow any agenda of societal revolution anymore. Contemporary “neuropsychedelia” – a term coined by the anthropologist Nicolas Langlitz – has absolutely nothing to do with a political propaganda à la Timothy Leary. So there is a chance that psychedelic research will even enter mainstream biomedical research, at least to a certain degree. In the case of ketamine, this is already taking place.

Suppose that you had all means of scientific investigation ready to use, which question would you like to have answered?

The central unanswered question still is – and will probably be for a very long time – how consciousness emerges from brain processes. To have a brain seems a necessary requirement for consciousness. But is it sufficient to fully explain the phenomenon? What western science seems to have long agreed upon, namely that “mind is what the brain does”, seems not so evident to me. Maybe consciousness is a fundamental characteristic of the universe, just like a negative charge is a fundamental characteristic of an electron, or gravity is a fundamental physical property of mass. And there is an even more fundamental question: Why is it that we are not mere stimulus-reaction-automata, but that we have conscious experiences so that we can rationally and emotionally navigate in a personal, subjective world? There are dozens of theories out there that aim to answer these questions, some very scientifically oriented, some less. However I have not encountered a single one that is really convincing or even practically verifiable. Personally I have the admittedly unscientific intuition that psychedelics might be key to the answer.

Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo)

Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo) by Richard M. Doyle, University of Washington Press, 2011.

In his book ‘Darwin’s Pharmacy: Sex, Plants, and the Evolution of the Noösphere (In Vivo)’, Penn State English professor Richard Doyle weaves an intricate argument that challenges some of our scientific presuppositions, like intentionality, evolution and language. He carefully analyses the influence psychedelics can have on perception and suggests an almost Copernican revolution. If we find the spiritual peak experiences evoked by plants and fungi function as “eloquence adjuncts”, and in turn we help these “bringers of beauty” reproduce, then whose intelligence can be said to influence whom?

Writing about trip reports, shamanism and cannabis pornography, Doyle tries to find a language that, like a psychedelic experience, transcends the subject/object dichotomy. His goal is to break down our ordinary way of thinking, so we can form a new perspective. A perspective in which consciousness is always already embedded in an ecological context, which means that everything we experience is dependent on ‘set and setting.’ Doyle seems to be apt when he renames these psychoactives as ‘ecodelics’ because these plants and compounds help us to perceive our interconnection with the ecosystems of our planet.

The result is a rich and challenging book in which form and content are inseparable, and the lines between facts and interpretations get blurred. The blending of his myriad ideas can only be understood in its entirety, which runs the risks that some of his key insights will be overlooked. But for the philosophically inclined reader with an open mind, it’s a well-written book that challenges many assumptions and should be read for that reason alone.

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Symposium Universiteit Utrecht: Psychedelics – Novel Applications for Depression

SymposiumUnitas

 Psychedelics – Novel Applications for Depression

An evening symposium dedicated to recent research into the potential anti-depressant effects and mechanisms of action of psychedelic drugs. Organized in collaboration with U.P.S.V. “Unitas Pharmaceuticorum”.

There’s a recognized need among therapists for more effective interventions for depression. The currently available psychopharmaceutical medications don’t work for everyone. What do we know about the effectiveness of psychedelics? To discuss these topics, we invited three young researchers, from three countries and three related disciplines. All presentations will be in English.

  • Tobias Buchborn is a German neuropsychologist, doing research at the Otto van Guericke University in Magdeburg. He studied the antidepressant potential of LSD in animals and will present his findings and implications for the clinical practice.
  • Mendel Kaelen is a Dutch neuroscientist working at Imperial College London. His talk will cover neuroimaging studies concerning the brain mechanisms of psychedelics and music, and their role in psychedelic-assisted therapy for treatment-resistant depression. You can read about his most recent publication here.
  • Tharcila Chaves is a Brazilian pharmacist, who is currently studying the effects of orally administered ketamine for therapy resistant severely depressed patients at the Medical Centre of the University of Groningen (UMCG).

There will be time for a plenary discussion and Q&A with the researchers afterwards. Please be on time!

Date: September 15th, 2015
Time: 19:00 – 22:00
Location: Marinus Ruppertgebouw (blue lecture hall), Leuvenlaan 21, Utrecht.
Tickets: €2,- for members Unitas Pharmaceuticorum / €7,50 for non-members. Sold on location.
Reserve your ticket(s) by sending an email to assessor1@upsv.nl (Unitas Pharmaceuticorum)
Also see the Facebook event page for updates and more information.

Symposium Utrecht University: Psychedelics – Novel Applications for Depression

Unitassymposium

Psychedelics – Novel Applications for Depression

An evening symposium dedicated to recent research into the potential anti-depressant effects and mechanisms of action of psychedelic drugs. Organized in collaboration with U.P.S.V. “Unitas Pharmaceuticorum”.

There’s a recognized need among therapists for more effective interventions for depression. The currently available psychopharmaceutical medications don’t work for everyone. What do we know about the effectiveness of psychedelics? To discuss these topics, we invited three young researchers, from three countries and three related disciplines. All presentations will be in English.

  • Tobias Buchborn is a German neuropsychologist, doing research at the Otto van Guericke University in Magdeburg. He studied the antidepressant potential of LSD in animals and will present his findings and implications for the clinical practice.
  • Mendel Kaelen is a Dutch neuroscientist working at Imperial College London. His talk will cover neuroimaging studies concerning the brain mechanisms of psychedelics and music, and their role in psychedelic-assisted therapy for treatment-resistant depression. You can read about his most recent publication here.
  • Tharcila Chaves is a Brazilian pharmacist, who is currently studying the effects of orally administered ketamine for therapy resistant severely depressed patients at the Medical Centre of the University of Groningen (UMCG).

There will be time for a plenary discussion and Q&A with the researchers afterwards. Please be on time!

Date: September 15th, 2015
Time: 19:00 – 22:00
Location: Marinus Ruppertgebouw (blue lecture hall), Leuvenlaan 21, Utrecht.
Tickets: €2,- for members Unitas Pharmaceuticorum / €7,50 for non-members. Sold on location.
Reserve your ticket(s) by sending an email to assessor1@upsv.nl (Unitas Pharmaceuticorum)

Also see the Facebook event page for updates and more information.

The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity

Abstract

Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin’s effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual–limbic–prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders.

Kraehenmann, R., Schmidt, A., Friston, K., Preller, K. H., Seifritz, E., & Vollenweider, F. X. (2015). The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity. NeuroImage: Clinical. https://dx.doi.org/10.1016/j.nicl.2015.08.009
Link to full text

Does LSD enhance the emotional response to music?

Aside from its hallucinogenic properties, LSD is known to have noticeable effects on emotion. This is one of the reasons why psychedelics were used in psychotherapy in the 1950s and 60s, hypothesizing that they facilitate emotional release and insight  [1][2]. Similarly, music can evoke emotion and was also a component in psychedelic-assisted psychotherapy, for aiding emotional arousal and release, and in promoting the occurrence of peak or spiritual-type experiences [3][4]. Working at Imperial College, London, neuroscientist and OPEN board member Mendel Kaelen and colleagues conducted a study [5] aiming to explore the significance of music in psychedelic-assisted psychotherapy. Using a placebo-controlled setup, the study sought to test the hypothesis that the emotional response to music is enhanced on LSD. The research team also investigated the role of music in occasioning peak or spiritual-type experiences.

Ten participants attended two study days. During one such day, they received a placebo (10ml saline), while on the other day they were given between 40 and 80 μg of LSD, with roughly a week in between. The design was single-blind, which means participants were blind to which condition they were in, but researchers were not. Participants listened to a playlist of five different (mostly neo-classical and ambient) instrumental tracks on each of the two study days, with the order of the playlist counterbalanced across participants. In order to assess the emotional response to the music, participants were asked how emotionally affected they were by the music, which served as the primary outcome. Furthermore, the Geneva Emotional Music Scale (GEMS-9) was used to investigate the specific factors of the participants’ emotional experiences, consisting of nine subcategories of emotion (wonder, transcendence, power, tenderness, nostalgia, peacefulness, joyful activation, and tension). The results showed that the mean scores for the emotional response to music were significantly higher for the LSD condition than for the placebo. Additionally, all nine factors on the GEMS-9 scored higher in the LSD condition than in the placebo, with significant increases for the items “wonder”, “transcendence”, “power” and “tenderness”. Correlational analyses showed a significant positive relationship between ratings of intensity of drug effects and emotional arousal to music.

The finding that LSD enhances the emotional response to music supports the popular assumption that music has more significance under the influence of psychedelic drugs. Emotions of transcendence and wonder are traditionally thought of as core constituents of peak and spiritual experiences [6][7]. This led the authors to infer that the combination of LSD and music may increase the likelihood of having spiritual-type or peak experiences. Moreover, these experiences have been shown to correlate with sustained improvements in well-being and life satisfaction [8] and also with increases in the personality trait of openness [9], which supports the view that music is an important element in psychedelic-assisted therapy.

Due to this being a pilot study, it does come with its limitations. Small sample size and musical genre selection mean that results cannot be generalised to a larger population. Also, participants could have guessed the purpose of the study, meaning the results could reflect their own or the researchers’ expectations. Additionally, results could be attributed to the effect of LSD alone, rather than the specific effect of music in combination with the drug.

When asked about the implications of his study for future research, Mr. Kaelen told us these are just humble first steps in helping build an evidence-based approach to psychedelic therapy. “It’s important to start a discussion on the role of music and the importance of the setting in general within psychedelic therapy,” Kaelen said. “Due to the study’s limitations, future studies have to come up with different designs and more detailed research questions.” Kaelen also mentioned research already underway at Imperial College, including brain imaging studies with FMRI and MEG, which aim to investigate which brain mechanisms are involved. He also emphasised the importance of translating elements into clinical work. “A clinical trial, now in progress at Imperial, uses psilocybin for treatment-resistant depression. Part of this study looks at the role of music, which will hopefully further our understanding of how music and psychedelic therapy work together.”


[1] Busch AK, Johnson WC (1950) L.S.D. 25 as an aid in psychotherapy; preliminary report of a new drug. Diseases of the nervous system 11: 241-243

[2] Leuner HC (1983) Psycholytic therapy: Hallucinogenics as an aid in psychodynamically oriented psychotherapy In Psychedelic Reflections, ed. Grinspoon L & Bakalar JB, pp. 177-192: Human Science Press

[3] Bonny HL, Pahnke WN (1972) The use of music in psychedelic (LSD) psychotherapy. Journal of music therapy: 64-87

[4] Grof S (1980) LSD Psychotherapy. Hunter House Publishers, US.

[5] Kaelen et al. (2015) LSD enhances the emotional response to music . Psychopharmacology [Abstract]

[6] Maslow AH (1993) The Farther Reaches of Human Nature. Arkana

[7] Richards WA (2009) The rebirth of research with entheogens: lessons from the past and hypotheses for the future. The Journal of Transpersonal Psychology Vol. 41: 139-150

[8] Griffiths RR, Richards W, Johnson MW, McCann U, Jesse R (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of psychopharmacology 22: 621-632

[9] MacLean KA, Johnson MW, Griffiths RR (2011) Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of psychopharmacology 25: 1453-1461

Versterkt LSD de emotionele reactie op muziek?

Music_Psychedelic_pictureNaast zijn hallucinogene eigenschappen staat LSD erom bekend merkbare effecten te hebben op emotie. Dit is een van de redenen waarom psychedelica in de jaren vijftig en zestig werden gebruikt bij psychotherapie, onder de hypothese dat ze emotionele bevrijding en inzichten helpen bereiken [1][2]. Muziek kan op soortgelijke manier emoties oproepen en was ook een onderdeel van psychedelica-ondersteunde psychotherapie, ter bevordering van emotionele prikkeling en verlossing, en om te helpen ‘piek’- of spirituele ervaringen op te roepen [3][4]. Mendel Kaelen, als neurowetenschapper werkzaam bij het Imperial College te Londen en OPEN bestuurslid, en zijn collega’s, voerden een onderzoek [5] uit met als doel de significantie van muziek bij psychedelica-ondersteunde psychotherapie te verkennen. Het onderzoek richtte zich op het toetsen van de hypothese dat de emotionele reactie op muziek wordt versterkt door LSD, gebruikmakend van een placebo-gecontroleerde opstelling. Het onderzoeksteam onderzocht ook de rol van muziek bij het opwekken van piek- of spirituele ervaringen.

Tien deelnemers woonden twee onderzoeksdagen bij. Op een van die dagen kregen ze een placebo (10ml zoutoplossing), terwijl ze op de andere dag tussen 40 en 80 μg LSD kregen, met ongeveer een week ertussen. Het ontwerp was enkelblind, wat betekent dat de deelnemers niet wisten in welke toestand ze verkeerden, maar de onderzoekers wel. Deelnemers luisterden naar een afspeellijst van vijf verschillende instrumentele nummers (voornamelijk neoklassiek en ambient) op beide onderzoeksdagen, waarbij de volgorde van de nummers door de deelnemersgroep heen evenredig werd verdeeld. Om de emotionele reactie op de muziek vast te stellen, werden deelnemers gevraagd hoezeer ze emotioneel werden beïnvloed door de muziek. Hun antwoorden vormden de hoofdzakelijke uitkomst van het onderzoek. Verder werd de Geneva Emotional Music Scale (GEMS-9) gebruikt om de specifieke factoren van de emotionele ervaringen van de deelnemers te onderzoeken, bestaande uit 9 subcategorieën van emotie (verwondering, transcendentie, kracht, zachtheid, nostalgie, vredigheid, speelse activering en spanning). De resultaten lieten zien dat de gemiddelde scores voor emotionele respons op muziek significant hoger waren voor de LSD-toestand dan voor de placebo. Daar bovenop bleek dat alle negen factoren van de GEMS-9 hoger scoorden bij de LSD-toestand dan bij de placebo, met significante toenames bij de aspecten “verwondering”, “transcendentie”, “kracht” en “zachtheid”. Verbandzoekende analyses lieten een significante positieve relatie zien tussen de aangegeven intensiteit van de effecten van de toegediende middelen en de emotionele prikkeling door de muziek.

De bevinding dat LSD de emotionele reactie op muziek versterkt ondersteunt de populaire aanname dat muziek meer betekenis heeft onder invloed van psychedelica. Overstijgings-emoties (transcendentie) en gevoelens van verwondering worden van oudsher gezien als kernelementen van spirituele of piekervaringen [6][7]. Hieruit leidden de onderzoekers af dat de combinatie van LSD en muziek de kans op het hebben van spirituele of piekervaringen kan vergroten. Bovendien is van deze ervaringen in het verleden aangetoond dat ze in verband kunnen worden gebracht met blijvende verbeteringen in gevoelens van welzijn en levensblijheid [8] en ook met toenames in de persoonlijkheidseigenschap van openheid [9], wat de opvatting ondersteunt dat muziek een belangrijk element in psychedelisch-ondersteunde therapie is.

Aangezien dit een pilot-onderzoek is, zijn er beperkingen aan verbonden. Een kleine populatievertegenwoordiging en de selectie van muziekgenres betekenen dat de resultaten niet kunnen worden gegeneraliseerd voor een grotere bevolkingsgroep. Ook kunnen de deelnemers hebben geraden wat het doel van het onderzoek was, wat betekent dat de resultaten zouden kunnen voortkomen uit hun eigen verwachtingen, of die van de onderzoekers. Daarbij zouden de resultaten ook alleen aan het effect van LSD kunnen worden toegeschreven, in plaats van aan het specifieke effect van muziek in combinatie met het middel.

Op de vraag naar de implicaties van zijn onderzoek voor toekomstige studies, zei dhr. Kaelen ons dat dit slechts bescheiden eerste stapjes zijn in het bijdragen aan een door bewijs geschraagde aanpak van psychedelische therapie. “Het is belangrijk om de discussie aan te gaan over de rol van muziek, en meer algemeen over het belang van de juiste setting, bij psychedelische therapie,” zegt Kaelen. “Vanwege de beperkingen van dit onderzoek moeten toekomstige studies andere ontwerpen en meer gedetailleerde onderzoeksvragen bedenken.” Kaelen noemde ook reeds aangevangen onderzoeken door het Imperial College, waarbij onder andere gebruik wordt gemaakt van hersenscans zoals fMRI en MEG, en die zich richten op de vraag welke hersenmechanismen hierbij betrokken zijn. Hij legde ook de nadruk op het belang van het vertalen van elementen naar klinisch werk. “Een klinisch onderzoek, dat momenteel aan het Imperial College gaande is, maakt gebruik van psilocybine voor behandelings-resistente depressie. Een deel van dit onderzoek kijkt naar de rol van muziek, wat hopelijk zal bijdragen aan een dieper inzicht in hoe muziek en psychedelische therapie samenwerken.”


[1] Busch AK, Johnson WC (1950) L.S.D. 25 as an aid in psychotherapy; preliminary report of a new drug. Diseases of the nervous system 11: 241-243

[2] Leuner HC (1983) Psycholytic therapy: Hallucinogenics as an aid in psychodynamically oriented psychotherapy In Psychedelic Reflections, ed. Grinspoon L & Bakalar JB, pp. 177-192: Human Science Press

[3] Bonny HL, Pahnke WN (1972) The use of music in psychedelic (LSD) psychotherapy. Journal of music therapy: 64-87

[4] Grof S (1980) LSD Psychotherapy. Hunter House Publishers, US

[5] Kaelen et al. (2015) LSD enhances the emotional response to music . Journal of Psychopharmacology

[6] Maslow AH (1993) The Farther Reaches of Human Nature. Arkana

[7] Richards WA (2009) The rebirth of research with entheogens: lessons from the past and hypotheses for the future. The Journal of Transpersonal Psychology Vol. 41: 139-150

[8] Griffiths RR, Richards W, Johnson MW, McCann U, Jesse R (2008) Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. Journal of psychopharmacology 22: 621-632

[9] MacLean KA, Johnson MW, Griffiths RR (2011) Mystical experiences occasioned by the hallucinogen psilocybin lead to increases in the personality domain of openness. Journal of psychopharmacology 25: 1453-1461

Noribogaine is a G-Protein Biased κ-Opioid Receptor Agonist

Abstract

Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicates that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50 = 9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6’-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations >1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders.

Maillet, E. L., Milon, N., Heghinian, M. D., Fishback, J., Schürer, S. C., Garamszegi, N., & Mash, D. C. (2015). Noribogaine is a G-Protein Biased κ-Opioid Receptor Agonist. Neuropharmacology. https://dx.doi.org/10.1016/j.neuropharm.2015.08.032
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5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis

Abstract

Serotonin [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][5-hydroxytryptamine (5-HT)] and glutamate have both been implicated in the pathophysiology of neuropsychiatric disorders but also in the mechanism of antipsychotic and hallucinogenic drug actions. Furthermore, close antagonistic interactions between 5-HT2A and metabotropic glutamate (mGlu)2/3 receptors have been established over the last decades on the basis of numerous electrophysiological, biochemical, and behavioral studies. Besides synaptic mechanisms, more recent findings suggested that heterodimeric 5-HT2A-mGlu2 receptor complexes in the prefrontal cortex may account for the functional crosstalk between these two receptor subtypes. In this review, we focus on in-vitro and in-vivo studies documenting the important relationship between 5-HT2A and mGlu2/3 receptors, with relevance to both normal behavioral function and psychosis.

Wischhof, L., & Koch, M. (2015). 5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis. Behavioural pharmacology. https://dx.doi.org/10.1097/FBP.0000000000000183
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