As 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 drugs, 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.