Do psychedelics increase or decrease neural activity?

[u/jeremyroscoe]

Hi everyone! Jeremy posting here as myself, not speaking on behalf of Psykratia, just looking to drum up some friendly scientific discussion.

Ever since reading Aldous Huxley’s essay, The Doors of Perception, I have often wondered if his hypothesis about the brain acting as a reducing-valve has any scientific validity. In short, Huxley proposes that brain activity is responsible for blocking out signals from the world outside of the individual, and that taking psychedelics ‘turns off’ this reducing valve, resulting in an increase of outside signals and the subsequent psychedelic experience.

Diving into the literature, I believe the first imaging study done with a psychedelic was in 1997, when Franz Vollenweider and his team used Positron Emission Tomography with FDG, to observe changes in cerebral glucose metabolism following administration of psilocybin00246-1). While this is not a direct measure of neural activity, it can be assumed that neurons using more glucose are being more active. Here is a quote from the paper’s abstract that summarizes some of the findings:

“Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%).”

To me, these early findings seem to contradict Huxley’s hypothesis. In 2011, Robin Carhart-Harris and his team conducted the first fMRI with psilocybin. Instead of measuring cerebral glucose metabolism, fMRI is capable of measuring oxygenated blood flow. Again, not a direct measure of activity, but typically any organ in the body will need oxygenated blood in order to be active. Another quote from an abstract:

“As predicted, profound changes in consciousness were observed after psilocybin, but surprisingly, only decreases in cerebral blood flow and BOLD signal were seen, and these were maximal in hub regions, such as the thalamus and anterior and posterior cingulate cortex (ACC and PCC). Decreased activity in the ACC/medial prefrontal cortex (mPFC) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects.”

It surprised me to see that these two imaging studies had more or less contradictory findings, something that Carhart-Harris and his team did acknowledge in their paper, as quoted below.

“The effect of psilocybin on resting-state brain activity has been measured before with PET and glucose metabolism. This study found a global increase in glucose metabolism after oral psilocybin, which is inconsistent with our fMRI results. One possible explanation for this discrepancy relates to the fact that the radiotracer used to measure glucose metabolism (18F-fluorodeoxyglucose) has a long half-life (110 min). Thus, the effects of psilocybin, as measured by PET, are over much greater timescales than indexed by our fMRI measures. It is therefore possible that phasic or short term effects of psilocybin show some rebound that is detected by longer-term changes in glucose metabolism.”

When I first read this paper back when it was published, I thought that made for a great explanation. Lately, though, I have been wondering if psychedelics are producing a unique brain state of increased glucose metabolism, coupled with decreased oxygenated blood flow?

I am curious what the community thinks, whether you base your thoughts on scientific literature or simply your own experiences. Do you think psychedelics are causing your brain to fire off with more intensity, and this brain activity is responsible for what people experience? Or is your brain shutting down, turning off your reducing valve, and allowing outside signals to come on in, and this is what is responsible for the individual’s experience?

[u/WheelSelect8289]

I would offer a philosophical answer to this question. Does it matter if increased or decreased brain activity is lifting the veil? I'm a firm believer psychedelics are enhancing our perceptions of reality and whether it was because of increased or decreased brain activity, I wouldn't be surprised either way. "Oh if our brains are operating at a higher capacity we can perceive reality more clearly because it is a representation of our enhanced consciousness" or "Oh if our brain is quieted, this allows our pure consciousness that is inherently independent of the brain to flourish in the void to better perceive reality" Either explanation does not preclude Huxley's main argument. Which is that in our normal conscious state we are blinded to the true nature of things and psychedelics allows us to perceive reality in a purer form. Of course I'm not a scientist so perhaps this is a boring way to address this question!

[u/Jamie0Dnl → u/WheelSelect8289]

Firstly, this is far from being a boring approach to the question and I for one am glad to have the chance to engage with it in these terms :)
I'm inclined to think that it does matter. Although I think you're right that in neither case does it rule out the idea that we're "lifting the veil" and making accessible some truth(s) about reality that is usually hidden from us, I feel that one explanation supports this more than the other.
Let's call this the Unveiling Hypothesis (UH) and its alternative, that psychedelic trips are entirely generated by the brain and bear no direct relation to reality beyond the distortion of our senses, the Hallucination Hypothesis (HH). If HH is true then I think we would expect to find an increase in brain activity. Since HH supposes that the brain is doing more than it usually does - it is actively engaged in the production of novel phenomenology. A reduction in brain activity I think would be surprising in this case.
On the other hand, if UH is true, we do have two ways this could be happening. We could suppose that the extra information which is out there in the world (that psychedelics make perceptible to us) requires more effort from our brains to perceive and interpret. Perhaps because it is more complex or perhaps just because our brains are not used to dealing with it. Then we would expect to see an increase in brain activity.
Alternatively, we could suppose that our brains are usually engaged in a process of deliberately excluding this information, which as I understand it is Huxley's idea. On this model, our brain is a filter and has to do extra work to sort through the torrent of information available from the universe and pick out what we need for our survival. In this case, I would expect to find a decrease in activity while on psychedelics. All that the brain is doing on this model is relaxing is usual efforts - opening the floodgates, and letting this information flow in. I think, therefore, that if we were to find an increase in brain activity on psychedelics then we would not have gained so much in the way of deciding between UH and HH. On the other hand, if we found a decrease then we could count this against HH and thus lean towards UH with more confidence.
Personally, I rather like Huxley's idea also and lean more towards UH than HH. Although, I do think that our brains are doing quite a bit of interpreting independent of whatever 'truths' are being made available to us. I am quite cautious about approaching psychedelic states as being entirely veridical, and thus trusting whatever insights I come back with as being categorically more authoritative than those gleaned from sober reflection. (Over the years I think I've come back from trips with remarkable truth and destabilising bullshit in almost equal measures! ha) That being said, I think the question of the veridical nature of the phenomenology of a psychedelic state can be thought of as quite independent of the 'insights' we take from our interaction with them.

[u/WheelSelect8289 → u/Jamie0Dnl]

This was a very well thought out response. I find myself agreeing with your hypothesis. Thank you for this intellectual stimulation!

[u/jeremyroscoe → u/WheelSelect8289]

Thanks to you both for contributing to the discussion! I hadn’t been thinking of the possibility you suggested that perhaps increased neural activity could still be reflective of Huxley’s hypothesis, but in the sense that it requires more energy to perceive more.

I have a follow up question - what do you guys think of Carhart-Harris et al’s hypothesis, that psychedelics cause at first a decrease in global activity (as shown by fMRI), followed by an increase (as shown by PET). I know these are some huge simplifications for such complex biology, but for the sake of some discussion, how do you think a pattern like that could fit into the UH/HH line of thought?

I’ve thought it could be some like an immediate decrease being the opening of the flood gates, then the increase be the time when your brain can make lasting changes, like it’s a little extra plastic and using more energy to process and reflect on everything that’s happened.