Propofol, Psilocybin, and the Kastrup Narrative
Truth or Fiction?
“We always thought that psychedelics produced these spectacular trips, the most intense memorable experiences of one’s life… we thought that they did that by lighting up the brain like a Christmas tree and for 10 years now we know that all psychedelics studied do precisely the opposite. They only reduce brain activity very, very significantly particularly in the default mode network which correlates with your ego... your sense of self when you’re not engaged in any activity or just thinking about something to yourself. So what psychedelics do is basically not only put your brain to sleep, but to simulate the death of your brain.” - Bernardo Kastrup
Propofol is a drug commonly used to place people under general anesthesia during medical procedures. General anesthesia induces a person to go completely unconscious in order to carry out invasive surgeries of various types. An experience of propofol can be described as the anesthesiologist asking the patient to count backwards from 10 down to 1 as the propofol is being intravenously administered. Generally speaking, by the time the patient reaches the number 8, they are unconscious and the medical procedure then proceeds to take place. The patient generally has no recollection of the time between when they first became unconscious to the time they wake up. There are generally no conscious experiences of any kind including a lack of dreams.
This lack of conscious experience during general anesthesia has been corroborated with various neurological measurements. Numerous electroencephalogram (EEG) studies showcase the distinct effects of propofol inducing a shift towards delta wave dominance in conjunction with a significant decrease in beta/gamma power (Xi et al., 2018; Qin et al., 2023; Wang et al., 1997; Ke et al., 2018). This comes as no surprise being that delta wave dominance is largely associated with naturally induced unconscious states such as non-REM sleep.
(Figure 3. (Ke et al., 2018) showing a distinct change of a reduction in faster oscillatory activity associated with propofol induced anesthesia.)
Positron emission tomography (PET) scans are utilized to measure glucose metabolism in the brain. Following propofol administration, a decrease in whole-brain glucose metabolism of up to 55% has been observed in numerous studies (Sun et al., 2008; Schlunzen et al., 2011; Laaksonen et al., 2018; Jeong et al., 2006; Alkire et al., 1995). This is also not surprising being that a significant decrease in glucose metabolism has also been observed in non-REM sleep stages compared to wakefulness and REM sleep (Buchsbaum et al., 2001; Nofzinger et al., 2002). It seems logical that a decrease in neural metabolic activity coincides with a decrease in faster oscillations associated with conscious experience.
Functional magnetic resonance imaging (fMRI) is increasingly being utilized as a method to measure changes in cerebral blood flow associated with changes in conscious experience. Propofol has been observed to induce a decrease in blood oxygen level-dependent (BOLD) signaling throughout the cortex, hippocampus, and amygdala associated with it’s sedative effects (Liu et al., 2017; Quan et al., 2015).
If Bernardo Kastrup’s statement regarding all psychedelics inducing their effects by only reducing brain activity is in fact true, one would think that there would be essentially mirroring of the effects of propofol. This is due to the fact that this anesthetic has shown to reduce the faster neural oscillations associated with higher order processing, reduce whole-brain glucose metabolism by up to 55%, and inducing a global reduction in BOLD signaling. Utilizing 3 metrics of neural activity, this can undoubtedly be considered to have the effect of only a reduction in brain activity.
A 2016 human EEG study observed that psilocybin decreased alpha power while inducing a simultaneous increase in gamma power. A 2022 rodent intracranial EEG study found similar findings following psilocybin administration with a suppression of slower brain waves while seeing a significant increase in the faster gamma waves. These results have been replicated by an unrelated lab at the University of Michigan (Silverstein et. al, 2024). Intracranial EEG is considered to offer artifact-free brainwave signaling due to the electrodes being implanted within the brain rather than sitting atop the skull. These results within itself do not mimic the results of propofol and do not showcase only a reduction in brain activity. In fact, they allude to higher order conscious activity taking place based on the relationship between faster oscillatory activity and complexity of experience.
(Figure 2 (Silverstein et. al, 2024) showing a 100% increase in power spectral density of high gamma in the 120 Hz to 140 Hz range following psilocybin administration.)
A 1997 human PET study in the journal Neuropsychopharmacology cites data indicating that 15 to 20 mg of psilocybin increases whole-brain glucose metabolism by up to 25%. Similar results have been replicated in a follow up study (Vollenweider et. al, 1998) as well as amongst a different research team (Gouzoulis-Mayfrank et. al, 1999). This comes as no surprise being that multiple studies highlight the finding of increased glucose metabolism being essential for increases in gamma wave amplitude (Galow et. al, 2014; Nishida et. al, 2008; Dienel, 2018). Once again, these results do not showcase reduced brain activity or mimic propofol’s effects of decreasing whole-brain glucose metabolism by up to 55%.
A 2012 fMRI human study in the journal Proceedings of the National Academy of Sciences presents data showing that psilocybin induced a decrease in BOLD signaling. This data does indicate a reduction of brain activity offering some mimicking action of that of propofol. However, it’s been well documented that stimulation of the 5-HT2A receptor has vasoconstrictive effects. This means that there is a narrowing of the blood vessels from the activation of this receptor. Being that psilocybin stimulates the 5-HT2A receptor, the confounding reduction in BOLD signaling should not be entirely surprising. A 2021 study in the Proceedings of the National Academy of Sciences highlights the fact that glucose metabolism and BOLD signaling do not always follow a linear relationship. There can be instances when glucose metabolism increases as BOLD signal decreases or a decrease in glucose metabolism with a simultaneous increase in BOLD signaling. This indicates that there is more research needed in the space of fMRI in order to comprehensively understand the data being generated.
One thing is clear… propofol only reduces brain activity by every metric measured so far. This reduction seems to linearly coincide with the lack of conscious experience. By contrast, it doesn’t appear that psilocybin mimics this same reduction in brain activity. This should come as no surprise as the effects are distinctly different between both substances. Propofol essentially turns a person’s “lights out” while psilocybin induces intense visionary experiences.
Going further than just psilocybin, the increase in fast oscillatory activity from psychedelics have been observed in multiple human and animal studies involving Ayahuasca (Don et al., 1998; Stuckey et al., 2005; Schenberg et al., 2015; Tagliazucchi et. al, 2021), DMT (Acosta-Urquidi, 2015; Pallavicini et al., 2021; Timmerman et al., 2023; Glynos et al., 2024), 5-MEO-DMT (Acosta-Urquidi, 2015; Riga et al., 2018;) psilocybin (Pal et al., 2024), LSD (Goda et al., 2013; Brys et. al, 2023), & Ibogaine (Gonzalez et al., 2021). Scientific truths tend to be based on replication studies by unconnected research teams. If the same results are documented consistently, this tends to develop as a scientific truth. In regards to classic psychedelics consistently inducing increases in faster oscillatory activity, there are 15 human and intracranial animal psychedelic studies from 11 different research teams showcasing this effect.
It’s unclear where Bernardo Kastrup derives his information to keep attempting to propagate the narrative that psychedelics only reduce brain activity. If the data showed that psychedelics induced the effects of propofol in terms of EEG, PET, and fMRI… then yes, the statement could be considered technically correct. But that’s simply not the case so perhaps it’s time to reconsider the accuracy of the desired narrative as it’s based on a false premise.
Maybe email this article to Bernardo at bernardo_kastrup@hotmail.com and get him to clarify why he believes he is correct in light of the data presented.
P.S. It is becoming increasingly more likely that the hypothesis of Dr. Stuart Hameroff is correct based on his idea that the psychedelic experience is taking place at a much faster speed than baseline consciousness. Future research focusing on high gamma and above 150 Hz needs to take place regarding psychedelics as well as the emerging technology called the Dodecanogram (DDG) that can purportedly measure activity at a much faster speed in the terahertz range.
(Figure 1C from the 2022 Intracranial EEG Animal Study. There appears to be a potential trend of increased power at faster bandwidths of oscillatory activity associated with psilocybin administration. At this point we can only speculate that the chart would continue to rise at bandwidths above 150 Hz.)