2022 was a decidedly volatile year in the field of psychiatry. In July, a study led by Dr Joanna Moncrieff (BizNews interview with Dr Moncrieff embedded below) found that there was no convincing evidence that depression is connected with low serotonin, let alone caused by it. In November, while the psychiatric profession and, perhaps more significantly, the millions of people taking antidepressants were still reeling from Moncrieff’s findings, a study co-authored by Dr David Erritzoe was published which provided the first direct evidence that serotonin release is blunted in the brains of people with depression. BizNews spoke to Erritzoe who explained the findings of the brain imaging study which is sparking debate within psychiatry about the so-called serotonin hypothesis of depression and challenging the findings of Moncrieff’s controversial study. Erritzoe, who is the Clinical Director in Centre for Psychedelic Research and Clinical Senior Lecturer in Psychiatry at Imperial College London, also provided fascinating insight into Imperial’s novel studies investigating the brain mechanisms and therapeutic potential of MDMA, ketamine and classic psychedelics. – Nadya Swart
Please see timestamped topics below
00:26: How Dr Erritzoe landed up in the unique professional niche of neuropsychopharmacology and psychedelic research
04:08: The uses of PET (positron emission tomography) imaging
04:50: The methodology and design of Erritzoe’s study which found that brain serotonin release is reduced in patients with depression
08:35: The drug used in the study
11:16: Why the study participants chosen were individuals who were not taking antidepressants
13:48: Response to critics of the study who argued that the conclusions drawn are not proportional to the evidence presented
19:51: Serotonin release capacity resulting from depression/antidepressant treatment discussion
21:07: Response to Dr Peter Breggin’s claim that the only chemical imbalances in the brain are those that have arisen due to the use of psychiatric drugs
24:12: Response to Dr Peter Breggin’s claim that at its heart, psychiatry is about damaging the brain
28:55: Discussion around akathisia
33:03: Post-doc imaging research into the effects of the brain mechanisms and therapeutic potential of MDMA, ketamine and classic psychedelics
38:31: Whether these alternative therapeutics could potentially replace the widespread use of antidepressants
41:13: What sparked Erritzoe’s interest in researching these alternative therapeutics
44:51: Whether these therapeutics pose a threat to Big Pharma
Excerpts from the interview with Dr David Erritzoe
Dr David Erritzoe on the design and methodology of the serotonin brain imaging study
It’s the first sort of decent attempt to measure this release directly. That’s not necessarily the same as measuring extra synaptic extracellular levels in the brain of serotonin, because we are in a way manipulating the brain in order to be able to measure it. So, therefore the method is that you do a PET scan, a bit like what I explained before, and in this case it was a PET radiotracer that was binding the serotonin to a receptor. So, we have a range of receptors, 14 or something like that in the serotonin system. This is one of them. It’s mainly postsynaptic and as postsynaptic, it’s not in the cortex of the brain and it obviously is a receptor of interest for me and others working in the field of psychedelics, because it’s actually the same receptor that psychedelics stimulate and [thereby] induce the psychedelic effects.
So you can give that tracer and then you can quantify the density of that receptor in the different cortical brain regions. And then what we do here when we want to measure a transmitter, so not just the receptor but the actual transmitter, we need to manipulate the system. So you can either try to decrease the levels of serotonin or increase it and then do another scan. And then the idea is that the difference in the serotonin available on the synapse will then compete differently with the PET tracer sitting on the receptor.
So, if you do something that increases the levels of serotonin, you will then get less binding of the radiotracer in the second scan after you have done that compared to the one done before. So, the baseline. Then you can subtract the two scans and get a measure of the difference, which is then a measure of how much serotonin was released and competing with it. Or it could be that the serotonin that was released by the agent that you give, in this case it was dexamphetamine, and it could lead to internalisation of the receptors. Either/or, there’s an effect of the serotonin that you’re then picking up by the second PET scan. So, that’s the concept.
And it’s the same principle that has been successfully used, I would say, in the dopamine field. There you had PET radio traces that have worked and behaved nicely for this to work. So therefore a lot of studies, not a lot, but a decent amount of studies have been done over the last decades measuring dopamine release. So instead, then you use a dopamine tracer and you give something that releases dopamine.
Response to Dr Peter Breggin’s claim that at its heart, psychiatry is about damaging the brain
It’s very bold and to me a bit too black and white. As a psychiatrist, I think I’ve taken more people off or reduced medication than I have put people on. That doesn’t mean that I think that they are doing only damage or they are deeply problematic or that they don’t work at all. I think that everything we use in psychiatry, as in other fields of medication, have side effects. And yes, there are some medications that actually have quite bad side effects and also negative health [effects] and even shortening of life expectancy and so on when it comes to antipsychotics. So, they are tricky compounds and they are not perfect.
However, when people are really unwell and they respond to the medication, then they serve an important purpose. And if you claim that any medication in psychiatry doesn’t work, then the effect sizes overall in psychiatry and in those kinds of medications are right in the middle of medicine. There are other fields of medicine that have lower effect sizes of the treatment used. So, you could apply the same [claim] to the whole of medicine then – that medication is just wrong, you should never use medication. And again, I would say that it starts becoming very black and white. I’m not claiming or blindly prescribing antidepressants in my practice.
Investigation of the brain mechanisms and therapeutic potential of MDMA, ketamine and classic psychedelics
We have been doing a lot of work with that and imaging studies to see how the effects on the brain of these drugs are while the drugs are working acutely. So, obviously psychedelics are a special kind of medication in the sense that when they’re given a full dose to induce a psychedelic experience, then they are given a rare occasion. So a few sessions, maybe even just a single session of these in these research studies, and then you can measure the acute effect of this altered state of consciousness that they induce. You can also, if you test the psychedelic treatment more sort of as a therapy for a patient population, you might do the imaging before and at a later point in order not to interfere too much with the therapy session when the drug is working, which can obviously be quite distracting to have to in the middle of a psychedelic experience.
We are doing a range of studies and have done I think some of the first studies in the modern era of psychedelics with depression and also done some of the early imaging work with a range of these compounds. I mean, there are also other groups that have done some imaging work even some decades ago, but very little. And we have then done some more studies trying to understand these drugs. We have done imaging with MDMA, LSD, DMT, psilocybin and ketamine.
Read Also:
- Meet Dr Joanna Moncrieff – the psychiatrist who capsized the depression, serotonin hypothesis
- Further evidence debunking the serotonin depression hypothesis theory
- ‘At its heart, psychiatry is about damaging the brain’ – Dr Peter Breggin, the “Conscience of Psychiatry”
