How do psychedelic drugs work on the brain?

okay so I'm a postdoc working for David nuts at Imperial I've been working researching psychedelic drugs for the last five years or so I completed my PhD four years ago and been working on really just this subject matter for the last five years so I'll try and give you the basics first we'll start with the term itself psychedelic what does it mean and where does it come from well when you hear psychedelic most people think about psychedelic art and really it conjures up ideas of psychedelic culture and so you might think of geometric Colusa nations and colorful patterns and this kind of thing the kind of heart and iconography that you associate with the 60s but it's actually quite far from where the term actually originates so in the mid-1950s a British psychiatrist Humphry Osmond was carrying out work with mescaline and LSD Aldous Huxley the the writer and intellectual learnt of Bosmans work and he was very interested in in the idea of these drugs they he sought out Humphrey and asked whether he would provide him with some mescaline and supervised his own psychedelic experience so after some deliberation Osmond was worried about sending the great Aldous Huxley mad that he did actually relent and he provided him with some mescaline and and all this Huxley had an incredibly profound experience which he wrote about in his famous book the doors of perception so in conversations between these men after all this had had as experience they were looking for a useful word that could define and describe this class of drugs because previously they'd really just been referred to as hallucinogens it also been looked at in the context of models of psychosis there was an idea that they generate some of the symptomatology of the psychosis or schizophrenia but these men thought that the the current words didn't really capture the essence of what these drugs do and how they change consciousness and maybe how they work in the brain so us Huxley had suggested a term which husband Osmond wasn't very sort of impressed with and he came up with his own and he actually combined the Greek word for mind or soul psyche with the word DeLoss apologies for my translation but so DeLoss means to make visible or clear or to manifest so in combination these words describe the drugs as mind manifestos or mind Ravidas and so already there's something you know quite interesting these guys are trying to capture some key property of these drugs and they really think that the primary property is one of making the mind manifest so that's for me as intriguing in itself that there should be aspects of the mind which aren't normally available to consciousness and these drugs might be used used as tools to get at those aspects of the mind so why study psychedelics well there's been some interesting recent work carried out in the u.s. that has administered quite a large dose of psilocybin the compound found in magic mushrooms so they've administered a large dose of psilocybin tea a relatively large sample of research participants and they found that two thirds of these participants described their experience as being one of the most profound of their whole lives within the top five most profound experiences of their lives and so when asked what that means what does that translate to they would say it was comparable to such things as the birth of their first child or the death of somebody very close so so it really was up there with you know major life event so again we've got we've got some context here which is helping to communicate really that these drugs profoundly affect consciousness that are interesting scientifically this psychiatrist was working with LSD in the 1960s and he was particularly effusive about these drugs and their potential he said that psychedelics use responsibly and with proper caution could be for psychiatry what the microscope is for biology or the telescope is for astronomy these tools make it possible to study important processes that under normal circumstances are not available for direct observation so inspired by these these findings and particularly stanislav grof actually is an interesting chap you know I've become very interested in psychedelics in the question of how they work in the brain given that they have such profound psychological effects we it's it's a natural inference to think that you know learning how they change brain activity to produce these effects they're going to tell us some very important things about how consciousness is produced in the brain so most of my works been with psilocybin and this is a compound found in magic mushrooms fortunately it's out of season at the moment it's not much you see so you won't be getting your iPhone's out and snapping his picture and going hunting at the end of it all go tomorrow but um so what's striking about psilocybin and its metabolites psilocin is the similarity of its molecular structure to the endogenous neurotransmitter in the brain serotonin so I've got a pointer now is here's psilocin this is what psilocybin is broken down to his serotonin so this is found in all of our brains in quite high concentrations and it's a very important neurotransmitter involved in modulating sleep and mood cognition lots of things that we do and it's really quite striking that only a small change in its molecular structure confers such a profound effects on consciousness when these drugs are administered to people in the mid-1980s it was found that there's a strong positive correlation between a psychedelic drugs affinity for a particular serotonin receptor in the brain and its potency so drugs that are stickier at the serotonin 2a receptor this subtype of serotonin receptor are more potent so to help illustrate that rule the classic psychedelic LSD is particularly sticky at the serotonin receptor the serotonin 2a receptor and it's also incredibly potent it's the most potent psychedelic drug whereas mescaline you require quite large amounts of it to produce hallucinogenic psychedelic effects and it is significantly less sticky where it has a lower affinity at the serotonin 2a receptor so really we've got some important clues here about how the drugs working in the brain it's also been found that if you block this subtype of the serotonin receptor the serotonin 2a receptor and then you give a psychedelic drug psilocybin then you won't get the psychedelic effects that you normally would so it completely attenuates the psychedelic effects of psilocybin so this serotonin 2a receptor is important clearly for how these drugs work in the brain so then it's important to know whereabouts in the brain is this receptor so pet work PET imaging work in humans has found that the serotonin 2a receptor is particularly highly concentrated in the cortex of the brain so that's the outer layer of the brain rather than the subcortical structures and it's also especially highly expressed in what are referred to as multimodal law or high-level structures in the cortex so rather than for instance the visual cortex which is has a very specific function or the motor cortex you know the concern with really only one only one modality these high-level regions do more sort of general things and there's some interesting work looking at these regions at the moment in the context consciousness and high-level cognitive functions so without what else about serotonin 2a receptor well the cortex is organizing this layered fashion there's a number of different layers and there's a particular layer in the cortex layer 5 where you find again a very high concentration of these serotonin 2a receptor and this these cells here these large pyramidal cells in layer 5 of the cortex are the primary output layer of the cortex so they're very large and they do a very important function that they're thought to confer to the top-down information their activities supposed to provide contextual information about sensory input and other sensations what else well what happens when you stimulate the serotonin 2a receptor when it's activated by the serotonin or by a psychedelic drug well the effect of serotonin 2a receptor stimulation is to excite that host cell and make it more likely to fire so we know that serotonin 2a receptor important we know where it is we know that when a psychedelic binds and stimulates this receptor it excites that host cell so these are some basics so this is all low-level stuff what what's this really going to tell us about consciousness well most of my work has been looking at functional brain imaging and at this level we get a kind of overview of the brain we get a macroscopic rather than microscopic picture or brain function or what's going on in the rain and at this level at this network level it's actually easier to make mappings between brain function brain activity and brain processes to psychological phenomena so in our first study we used functional magnetic resonance imaging to measure blood flow in the brain and this study involved 15 healthy volunteers they had a mean age of 34 it was an 18 minute scan and there was a placebo scan to provide us with a baseline and then the drug scanned psilocybin they lay in the scanner and though there wasn't any behavioral tasks that they had to carry out they were simply resting there in this case with a fixation cross that they were supposed to just relax and look at so we go 2 milligrams of psilocybin this compares to about 50 milligrams of the drug given orally which compares to about it will say about 20 to 40 Liberty Cap magic mushrooms if you want to put it in a in a recreational context so here's the basic design we've got a baseline period and we actually administer the drug intravenously so there was an infusion of the drug over 60 seconds there was a pre drug baseline six minutes the drug went in over 60 seconds and the effects when the drugs given intravenously are actually incredibly rapid they come on very quickly and actually even before the end of the 60-second infusion people report feeling something so it's incredibly rapid onset and the effects are quite profound and then essentially we make a subtraction blood flow post infusion of the drug versus blood flow pre-infusion and then we see where there are any changes so the first observation we make when we do this research are the psychological ones it takes a little while to do the drainage imaging analyses so the first thing we get are just people's descriptions of the experience so these are some of them there's only a couple this volunteers said there was definite sin of lubrication or freedom of the cogs being loosened and firing off in all sorts of unexpected directions this one has said that everything became fragmented things were all in bits and it was very hard to hold it all together in the coat into a coherent stream so these descriptions are useful because they already kind of suggest mechanical processes they kind of give us clues about what might be going on in the braid and in that way they kind of assist the mapping that we make between the brain changes and the psychological effects so just to give you an introduction to something which will become important as you see the results there's a particular network in the brain which is attracting a lot of interest at the moment this network is metabolically hungry it receives a large amount of blood flow and it consumes a lot of glucose in the brain and it's also highly interconnected and regions within this network have very dense connections they serve as kind of connector hubs or transit hubs and really functionally we think that they may be very important for integrating information and also polling information and generally working as a kind of key center in the brain a kind of Orchestrator or conductor for brain function so to help you along an analogy might be a capital city in a country so it's it's there are regions in the brain that is especially important that particularly important it seems for consciousness and normal cognition just as a capital city is incredibly important for the functioning of a country for instance what else we know about the default by Network well it undergoes significant ontogenetic development so that means it develops significantly over through maturity from infancy to adulthood it's also the regions within the default mode Network have also undergone significant evolutionary expansion so they're much bigger enjoyments than they are in primates for instance it's like I said it's these regions are especially metabolically active more so than elsewhere in the brain for instance this posterior cingulate cortex hub this region that's highlighted will become increasingly relevant to my talk because what I won't give a result like I've already yeah but it it consumes or rather it accounts for what they received 40% more blood flow than elsewhere in the brain so incredibly active region in the brain but there's a lot of uncertainty about what its function actually is and the sort of discoverer if you want of this default mode network has referred to it even as the brain's dark energy so making the analogy to dark energy in cosmology it's something that's there but we can't easily study it we don't really know what it does it's engaged during self reflection complex mental imagery mental time travel so that's thinking far into the future or contemplating back into the past also theory of mind or trying to understand and interpret and make inferences about somebody else's thoughts and state and metacognition in general which means thinking about thinking so all these functions are associated with this default mode Network recall the discoverer of this networks also referred to as being the orchestrator of the self others have suggested that it may even be the receipt of our personality of our sense of self or agency or identity or ego if you like that term default mode network in depression well connectivity within the default mode network has been found to be increased or elevated in people with patience with depression and the stronger the connectivity between two particular hubs in the default mode network is posterior cingulate cortex hub and this medial prefrontal hub the stronger the connectivity between these regions the higher the rumination scores in patients with depression so the more they chew things over the more they're inside their own heads thinking about how terrible generally they are and you know dwelling on lots of negative things so to get on with our results on what we found that's what I've just said provides a kind of background to help you understand our results and what they mean so this is what we found on notes month this is her so the results were quite surprising they weren't they will have that surprising but they were quite surprising we're actually expecting to find increases in brain activity based on people's descriptions of the psychedelic experience has been incredibly profound somehow kind of consciousness is expanded it's more than it is during normal waking consciousness so we thought that we might see on a very simple level more brain activity more brain blood flow and we actually saw the opposite so when I discussed these with David Nutt he said well you know this kind of gives us confidence when you when you have a hypothesis and you test it in science and you find completely the opposite you can actually you know start thinking that you found something very important you know because there are kind of implicit biases to to support your own hypotheses but when they're kind of sort of shattered then then you've got something really interesting to get to understand and to know what's going on so this is what we found we found decreased blood flow in the brain and we found it in particular regions of the brain and those were regions of the default mode Network such as the posterior cingulate cortex the medial prefrontal cortex other hubs in the brain like the thalamus subcortical II and other high-level cortical regions what was quite striking was these lower-level visual or sort of specific cortical regions like the visual cortex or the motor cortex they didn't really show marked decreases in blood flow so the highest decreases seemed to be constrained to these hub structures in the brain and this may provide some clues about what the drugs doing in the brain to change consciousness it just shows you the very dense connectivity in these regions that were showing decreased blood flow after psilocybin we also found that there was a correlation between the magnitude of the decreases in these regions and the self-rated intensity the subject of intensity of the drug effects so those who had very profound intense experiences with the drug had the biggest decreases in blood flow in these regions and we actually replicated this results doing another study using another fMRI modality the bold signal of fMRI and we found decreases in that study as well so that that kind of gave us further confidence that's in 30 subjects now so we thought you know we were onto something here and we really did find something important about how these drugs work in the brain it's a provide a kind of outside context for these results it's interesting to look at other studies and other brain imaging studies and and how the brain changes under other altered states of consciousness so looking at meditation it's been found that consistent regions to those that we found in our study show decreased activity during meditation and particularly so in experienced meditators that's just to show the comparison between the meditation results in our sadhus on results and particularly in in this medial prefrontal region of the brain here so decreases with meditation and also with psilocybin what's interesting is that this region is quite reliably overactive or hyperactive in depression and it's also been found that a number of effective treatments for depression or normalize dis over activity in the medial prefrontal cortex so that includes SSRIs cognitive behavioral therapy sleep deprivation which can be very effective for depression electroconvulsive therapy which is very effective although it's controversial treatment and placebo and those who respond to placebo will actually find the same normalizing of this over activity that you can you find in depression also deep brain stimulation so an invasive procedure actually targeting key nuclei in the brain that are overactive these these medial prefrontal regions and essentially shutting them off with electrical stimulation that's also been found to reduce metabolism and blood flow in the medial prefrontal cortex also ketamine which is emerging as an effective short-term treatment for depression that also decreases medial prefrontal activity so this hopefully provides a context and really these brain imaging work this brain imaging work together with some recent clinical studies involving psilocybin kind of gave us the confidence to apply for a grant to the MRC to do a study a clinical trial in patients with depression giving them psilocybin intravenous psilocybin to try and decrease their depressive symptomatology so we were successful in that and really we were kind of spurred on by a lot of the reports of our volunteers also the the clinical work that's been done before looking at for instance anxiety in patients with end-stage cancer that have existential anxiety around death psilocybin skin been given to these patients and it's been found that it will reduce anxiety ratings and also ratings of depression and and these effects seem to persist so this is actually six months on from a single dose of psilocybin you'll find that depressed depression scores will still be significantly reduced so this volunteer was from our own research and she said after her experience with psilocybin that never since Thursday I'd say I found it much easier to engage in the moment to attend to the here and now there was some fountains and the water was being blown by the wind this is after she left the scam she wasn't hallucinating absence allowing the Sun to highlight the spray I could have watched it for ages somehow the beauty was enhanced whatever it was it's lasted like the sun shining through the leaves this morning it made me slow down my walk to work and enjoy the experience with flickering over my face this was quite consistent we had a lot of people describing is kind of afterglow after their experience actually the acute experience itself is often not enjoyable for people people describe it as being quite anxiety provoking it's strange they feel a kind of uncertainty in this strange state of consciousness and actually often people are pleased when it's over however you know that being said people do describe having a kind of afterglow after the experience that they feel good that somehow the burdens of life feel less weighty this is the kind of thing that people were telling us after their experience so what about how the drug works in the brain that's the key topic of the talk well one of the most useful measures that we've looked at with our work is functional connectivity so give you a very brief explanation of what functional connectivity is so essentially the activity in the brain when we use fMRI and bold fMRI to to record brain activity we find that it fluctuates in this sort of spontaneous manner it naturally goes up and down and if you look at sometimes distally separate sometimes quite remote regions in the brain and you look at their fluctuating activity sometimes you'll find that it's actually synchronous so here we've got a yellow trace and that's from I think it's from the PC see the posterior cingulate cortex an orange one and you can see that they're kind of synchronous they sort of go up and down in phase and this provides us some information about the kind of common function of these regions that are working together as if they're one whole system an integrated system so we see that here and these are actually regions that are deformed by network you can see the the activities going up and down in synchrony there's also other networks in the brain where activity sometimes shows a competitive or anti phase relationship this network here is concerned with kind of visual attention and focusing on on specific things engaging and intent intent attention right so what did psilocybin do two functional connectivity in the brain well we looked at the hippocampus first so we looked at regions in the brain where activity was synchronous with the hippocampus and those regions are shown in orange and then we looked at how connectivity with the hippocampus changed after Silas eyelid and this result was really quite striking because despite looking everywhere in the brain we found that it was specifically these default mode Network regions which fell out of sync with the hippocampus so usually these are kind of part of the same system these are subcortical nodes belonging to the default my network and yet under psilocybin there was a disintegration of their activity it became decoupled from from the hippocampus so that was quite interesting it's it's known that there's a correlation between the coupling strength between the hippocampus and the default mode Network regions the higher the coupling between these regions the more often we sort of exit the the here and now the present and the more we sort of daydream about the future or about the past so the more that we do that more we kind of introspect and fall out of the moment the stronger the coupling between these default mode Network regions so it's interesting in the context of psilocybin these are drugs that people describe as altering time perception people struggle to really fathom the passing of time and it all they sometimes say that time almost becomes meaningless so it may be that there's something going on here between coupling between the hippocampus and default mode Network regions and this changing in time perception that you see with psilocybin so some more network results we looked at a middle prefrontal region and another node at a default mode Network and these are in orange this is connectivity during baseline we also looked at that dorsal attention Network the one in blue in the previous image and these are regions that are functionally coupled to this region the seed region during pre drug conditions during baseline and this is what the drug did so again a decoupled activity within the network so it's essentially working to disintegrate these functional brain networks and we think that might account for some of this fragmentation of cognition that people are describing after they've had their experience so more recently we've used the brain imaging modality called magnetic and careful ography or M eg or Meg and this is a particularly useful brain imaging modality because it more directly records or measures brain activity it gets closer to the actual neural activity itself with fMRI you're always having to make assumptions about brain activity through this signal which is dependent on blood flow in the brain so you always have this kind of confound you're sort of looking looking at this surrogate marker of neural activity whereas with M eg you get much closer to the actual oscillations in neural aggregates in the brain and then we can look at how psilocybin affects these oscillations so this study again was in 15 healthy volunteers was a simple design with a five-minute pre infusion of psilocybin baseline and then a 5 minute post infusion period where we would look at the changes caused by psilocybin again it was a placebo controlled design and we did a basic subtraction looking at activity post drug versus pre so the first thing we saw with the subjective ratings I'm going to summarize these for you because there's a lot primary effects actually with this dose of psilocybin and also with the mode of administration are generally perceptual however more profound effects to occur but they're more they're more variable they differ more from person to person but there were two effects that are particularly interesting because they correlated with the brain changes that we saw and those are this experience of the experience having a supernatural or magical quality somehow conjuring up sort of ideas that something metaphysical was going on when people scored this item high you'll see in a moment they had very marked changes in brain activity and another item which is particularly interesting because it kind of speaks to this default mode Network and what its function might be is this item I experienced a disintegration of my self or ego so all these items are the bottom five were significantly rate is significantly higher after psilocybin but these two items were ticked particularly interesting because they seem to explain or correlate with the brain changes that we saw so what were those changes well kind of reassuringly they were consistent with the fMRI results that we found so we saw decreases in oscillatory power after psilocybin and this was found in a range of different frequency bands from very slow oscillations in the brain as Delta frequency to much higher oscillations in the brainless high gamma frequency they were particularly marked in this alpha frequency band and especially located to the posterior cingulate cortex and other again high level cortical regions so what is what what does decreased oscillatory power mean well it actually means that the amplitude of the oscillations in that frequency band were more shallow they did the amplitude decrease because the the neurons essentially weren't oscillating as synchronously there was a D synchrony in the brain caused by the drug so those items that I highlighted there was a very striking finding when we looked at correlations between the different subjective ratings and particularly the decreases in alpha power in the posterior cingulate cortex that were especially marked so that kind of constraint where we were looking we also corrected for the fact that we were looking at all these different subjective I ratings all these different items and we found that the significance of this correlation still remained significant despite looking at so many different potential correlations so there was a highly significant effect where the the bigger the decrease in oscillatory power or the bigger the D synchrony in this region of the brain in this frequency band the higher people rated this item of experiencing a disintegration of their ego or of their self so that provides a quite an interesting clue that there's something important about alpha oscillations and potentially such a high-level phenomenon as our sense of self there are some interesting there is some interesting research and some reviews around the Alpha frequency and for instance it it increases through ontogeny so it's something like connectivity in the default mode network that seems to increase as people develop or mature into adulthood which again would map on to this idea that there's something important about this is default my network regions in relation to to the sense of self or the ego we've also found that there was a the other item which came up as being significant when we controlled for the sheer number of tests that we were doing was this one that refers to the perception of the experience having a supernatural quality or a magical quality this is interesting because particularly if you look at Freud Ian Cleary or psychoanalytic theory Freud said that in the absence of the ego consciousness is more magical it takes on a kind of regressive primitive quality and so it's interesting that these two items came up one concerned with the ego in the sense of self and this other one concerned with sort of reality testing and and magical thinking so in the absence of of sort of diligent reality testing then people will be more inclined to to have magical thinking it also speaks to people's descriptions of the experience having a kind of spiritual sometimes religious quality which is interesting so the brain is organized in a hierarchical fashion and this is kind of exemplified by the visual system this is quite complicated so I don't want to go into too much depth with it but essentially it was an extension of the make analysis we did and we looked at different cell types in the cortex using a modeling approach to see if we could discern how changes in activity in the different cell types could account for the effects that I've just shown you so when we ran this modeling approach we found that the particular cell types that came up as being significantly modulated were these deep layer pyramidal cells and they're the same as these layer 5 pyramidal cells where the serotonin 2a receptor is especially densely expressed so again we have this nice consistency where we know the the serotonin receptor through which the drug sort of initiates its effects we know where those receptors are and then when we're looking at the macroscopic level albeit with modeling here we find that there's a consistency between the effects that we see at that level and what we know based on where the receptors are in the brain so putting this in a context is slightly sort of a bit of a difficult inference to make but in a recent write-up of this work we've we talked about the evidence that these deep layer pyramidal cells are particularly concerned with top-down processing or providing contextual information for lower-level regions in the brain given that the brain is organized in this hierarchical way so if we're exciting these regions that provide context or provide throughout sort of high-level information for for information that comes in through our sensations then it may be that the the sort of contextual information might kind of contaminate consciousness so for instance if we have information coming in and there are regions high-level regions in the brain concerned with for instance seeing faces then if these modules become overactive then it may be that we start seeing faces where they don't actually exist so we've described this as being a kind of inference before evidence or impetuous inferences in other words another term that we use so the kind of predictive the inferential function of the brain is sort of sort of bleeding into consciousness and contaminating consciousness and this may explain why people have kind of visual distortions and see things such as faces in in visual scenes so for instance you know seeing a face in a tree for instance might speak to this aberration that's being caused by by the drug effects right this is very if there's the rest of it wasn't high-level enough this this is kind of trying to get to grips with the reports of people that they sometimes have spiritual or mystical experiences with psychedelic drugs so in systematic analyses or assessments of of the phenomenology of spontaneously occurring mystical or spiritual experiences this chap wilfred states identified one key component which seems to be universal in people's descriptions of their spiritual or mystical experience and that is the sense of oneness so the sense of everything being sort of related and he referred to it as this this unitary consciousness or unit of consciousness and it's consistent to some extent with William James's writings on the spiritual experience and it's also very consistent with people's descriptions of the psychedelic experience they refer to this sense of oneness so although this is very abstract there are actually some clues now from brain imaging about what might underlie such a such a strange and profound experience so just from our own work one of our volunteers said after their experience that that was real ego death stuff a total dissolving of the ego boundaries only existed as a concept or as an idea this volunteer said it was certainly quite difficult to know at times where I ended and where I melted into everything around me so again speaking to this notion of ego boundaries which is talks to the idea of having a distinct sense of self which is separate from the external world and this is sort of different to the spiritual experience where there's a kind of melding of the self with the external world there are no boundaries there is no self and there is no world as there's oneness so what might underlie that this is another description from from another team in the US one of their volunteers said there was a feeling of no boundaries I didn't know where I ended and my surroundings began somehow I was able to comprehend what oneness is so it's all speaking to the same thing so I talked earlier about functional connectivity and also talked about how activity and different brain networks sometimes has this competitive property to it as activity and one neck network goes down activity in another Network goes up interestingly the functions of these networks which show this competitive relationship are also very different so for instance we have the default my network which is concerned with introspection with a sense of self with looking inwards and then we have these attention networks which are consider concerned more with scrutinizing the external world and so in a way you could think of the development network as being self or subject or internal and these these other attention networks has been concerned with sort of objects outside oracle or external so they're kind of diametrically opposed both in their function and in the activity that underlies these networks so then what do we find with psilocybin well the interesting thing is that we find that this competitive relationship actually breaks down under the drug so instead of having this some natural competition between the networks we find that they're sort of behaving as if they're the same network that that there isn't there aren't two competing networks anymore there's just one and we think that this potentially may be related to the sense of oneness that people described under the drug what would support that idea would be that if we could find that in states where there's a related phenomenology or psychology to the psychedelic state if we found the same brain activity in those days then that would support this idea that there's something going on whether whether it's breakdown of competition relates to this experience of a sense of oneness so some states that share the similar phenomenology to the psychedelic experience well it's been found in schizophrenia that these this between network sort of competition does decrease the coupling between these networks increases because their competition is decreasing and particularly an early psychosis or in the at-risk mental state so in people who are showing risk risk factors for conversion to psychosis and that's particularly interesting because if you look carefully at the phenomenology of schizophrenia in general then you'll find that it's particularly in the early phase of the disorder that there's a strong similarity between the phenomenal phenomenology of the psychedelic state and that of what you see in this disorder also interestingly in deep meditation it's been found that this competitive relationship between activity in these two networks decreases and particularly in a form of meditation referred to as non-dual awareness which actually promotes the dissolution of subject object differentiation or or ego boundaries essentially so that's been found as well so there's this interesting consistency here where we're finding that in states that share a phenomenology to the psychedelic state we're also seeing the same neurobiological phenomena so this has led us to hypothesize that this may be underlying the disturbed ego boundaries that you see in all these states so very briefly a the most recent analysis we've looked at is this analysis referred to as meta stability and really this is looking at the stability of different brain networks over time and we found that the particularly high level networks in the brain it's not shown here but the default mode network is one of them when activity in or rather stability of activity in these networks increases rather sorry decreases over time when the networks become less stable this is what we see under psilocybin so there's a significant increase in the of instability or rather decrease in the stability of the networks over time their baby behavior becomes less predictable they become more chaotic so just to summarize we've seen decreased brain blood flow in the major transit hubs of the brain we see decreased integrity in key brain networks with psilocybin we've seen a marked decreases in the rhythmic structure of cortical activity after psilocybin we've seen that hyper excitation in these deep layer pyramidal cells occurs under psilocybin and we've seen that networks that usually have sort of competitive or positional activity become behave more like one under the under the drug so all these things have led us to make a kind of general theory of how these drugs are working in the brain and it relates to the idea of entropy or order and essentially a lot of work at the moment is talking about sort of there being as a sweet spot in brain activity where there's a perfect balance between complete disorder and sort of a complete order and it's at this sweet spot that cognition can be supple enough and flexible enough but also ordered enough not to be chaotic we think that there are certain states that that sort of exists towards a more chaotic sort of configuration and that would include REM sleep also early psychosis the sensory deprived State deep meditate restates the near-death experience and the psychedelic state and you'll find that the phenomenology in these state is related so the next stage to test this theory is to see whether whether there's a related neurophysiology in the psychedelic state to these different states other states which might exist on the other end of the pole would be things such as seizure where the activity in the brain is hyper synchronous sedation again even though it's quite a different state consciousness is lost but neural activity becomes more synchronous deep sleep and depression as well we think that this might be a sort of old overly stable state where a particular brain network may dominate the cognition so this is a kind of metaphor presented quite a lot of difficult stuff but if you want to take one thing home it might be that these drugs seem to work in the brain at least we're making the inference that these drugs seem to increase the sort of chaotic nature of brain activity it's notion of entropy is particularly interesting because as a measure it actually is a measure of our uncertainty about a system so as a system becomes more disordered it's hard to predict its state at any one time and we think that this may relate actually to the phenomenology that people experience a kind of uncertainty in their quality of consciousness as the brain networks become more chaotic in their behavior so I think that's my last slide then just to thank my boss David nuts and lots of funders and you for your attention Thanks you

Channel: Imperial College London

Views: 318,807

Rating: 4.9346304 out of 5

Keywords: imperial, college, london, science, university, UK, festival, drugs, psychedelic, party, rave, Trance, Mind

Id: jT5dZDnJ6J4

Length: 49min 53sec (2993 seconds)

Published: Wed May 29 2013

Reddit Comments

[u/mystery_disease]

TLDR: they make it much worse at predicting patterns.

But really, watch this guys stuff. Harris's, that is.

[u/empetrum]

Man this was fascinating.

The reduced activity in the default mode network is remarkable, since it is so active in people with depression.

This was far too interesting. Now I just want LSD.

[u/yogiebere]

I wonder how similar psilocybin is to lsd and dmt in terns of effects on the brain. Does lsd also limit blood flow to the brain?

[u/INTPtree]

Really gives insight into possible similarities with treatments for depression. It's really the only thing which has provided me long-term relief from depression symptoms.

[u/thehorsedogcontinues]

BTW Dr Harris said that the state of psychedelic inebriation promotes a brain activity pattern which is similar to one achieved by meditation. This is very interesting for me, because I practice mindful meditation and recently I tried it on LSD. It's usually difficult to achieve the mindful state, but this time it came to me with unprecedented ease, which is especially astonishing, that I did it mid coversation with my friend, and in an underground electronic music club, with the beats pounding nearby, and a lot of people everywhere.

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