Dale Bewan's final course project for the Coursera/University of Chicago course "Understanding the Brain: The Neurobiology of Everyday Life".

1. WHOLE BRAIN EFFECTS OF
TRYPTAMINE PSYCHEDELICS
by Dale Bewan
for the Coursera/University of Chicago course:
“Understanding the Brain: the Neurobiology of Everyday Life”

2. OVERVIEW / INTRODUCTION
• The aim of this presentation is to present the reader with a basic overview of the current
state of research and knowledge as to how tryptamine psychedelics have their effects
on the human brain.
• Tryptamine psychedelics influence a large number of brain areas, including but not
limited to:
• The posterior cingulate cortex (PCC)
• The thalamus
• The visual cortex
• These will be investigated in this presentation after some initial background information.
• At the end of the presentation is a slide unrelated to tryptamine psychedelics that
covers the ways in which the “Understanding the Brain: the Neurobiology of Everyday
Life” course has allowed me to better analyse events and phenomena around me in
everyday life.

3. INTRODUCING TRYPTAMINES
• Tryptamines are a specific class of chemical. Some tryptamines are vital parts of your normal brain
function such as serotonin and melatonin; others are psychedelic drugs such as psilocybin, DMT
(dimethytryptamine), and LSD[i].
• Psychedelic drugs are substances that produce a profound experience on the human mind. The word
“psychedelic” is a term coined from Greek, meaning “Mind Manifesting”[ii].
• Most psychedelics produce their primary effects through a complex (non-typical) agnostic effect on the
serotonin receptors 5-HT2A, 5-HT2C and 5-HT1A. Many psychedelics also have affinity for a large number of
other receptors[iii].
• Traditionally, it was thought that the 5-HT2A receptor activation was the ‘primary’ responsibility for the
psychedelic effects, since blocking this activation does block the effects; however further research shows
this is more complex, as removing the drug’s affinity for the 5-HT1A receptor also blocks these effects[iv].
This shows that the psychedelic action is perhaps more complex than originally thought.
• This presentation however will concentrate primarily on the ‘bigger picture’ effects on influence of the
drug on different regions of the brain as a result of these lower level receptor bindings.

4. INTRODUCING PSILOCYBIN
• The most well studied tryptamine for ‘whole brain effects’ to date is arguably
psilocybin. Psilocybin is found in “magic mushrooms” but can of course also be
synthesised in a laboratory if needed.
• Psilocybin itself is rapidly converted to psilocin in the body and it is in fact the
psilocin that is pharmacologically active. For ease of discussion however, most
research refers to ‘the effects of psilocybin’ even though this distinction is well
understood.
• The studies that have been performed with other tryptamine psychedelics tend to
agree with psilocybin studies apart from a few differences that appear to be
substance specific in some cases. Therefore we can generalise psilocybin studies
as potentially being valid for most – if not all – tryptamines.

5. TARGETS IN THE NERVOUS SYSTEM
• The primary effects of interest of the psychedelic tryptamines are on the central
nervous system (CNS). There may also be effects on the peripheral nervous system
(PNS) through activation of serotonin receptors in the intestinal wall for example,
but these are generally mild and not (yet) medically interesting/useful.
• Within the CNS, there is a plethora of effects, making it difficult – but not impossible
– to determine which effects are directly engendered by the drug and which are
follow-on effects of the drug’s behaviour on other systems.
• For the purposes of this presentation, we will limit our discussion to effects within the
brain specifically.

6. INSIDE THE BRAIN
• As described there is a plethora of different areas altered by the effects of tryptamines within the
brain.
• Over the next slides, we will discuss several of these effects as far as they are currently understood.
• It is important to note that due to legal concerns, it
was for many years very difficult to perform research
relating to psychedelics. As such, most research is
either ‘very old’ (1950s, 1960s – before we knew as
much about the brain as we do now); or very recent
and therefore representing ‘work in progress’ that
is subject to frequent change in our understanding.

7. THE VISUAL SYSTEM
• The most popular view of the effects of psychedelic substances is that of visual
distortions and hallucinations, so we will begin there.
• The visual cortex is – like all cortex – made up of many folds and shapes. As it happens
however, the image seen by the eyes can be directly mapped to this cortex (reversed
and flipped) if you were to physically unfold this area to a flat surface[v].
• The most consistent reported visual of psychedelic substances is that of specific patterns
appearing ‘overlaid’ over normal reality. It appears that these patterns are caused by
a kind of ‘data bleed’ in the visual cortex, prior to optic radiation passing the data to
the conscious mind.
• The patterns seen on psychedelics can be mathematically generated by
computationally creating a coordinate map of this area of the brain, ‘bleeding’ data to
physically nearby locations (that may not be visually nearby) and then ‘unfolding’ the
cortex[vi].

8. INFORMATION EVERYWHERE
• Another common experience with psychedelics is the feeling that one is ‘taking in a lot more information’.
• This is both a trick of the mind and in some ways accurate. In daily life, it is normal that your brain takes in a
large amount of information from the senses. This information is passed through the thalamus before being
routed to its final destination.
• One of the jobs of the thalamus is to organise or translate the data in a way that other parts of the brain will
understand. When doing this it has the additional function of acting somewhat like a filter.
• Under the influence of psychedelics, the thalamus reduces its activities
significantly (as indicated by fMRI blood flow measurements).
• In his book “The Doors of Perception”, the author Aldous Huxley
likened this function of the brain to the concept of a reducing
valve. When you take a psychedelic substance, the effectiveness
of this ‘reducing valve’ is limited – you open yourself up to the
opportunity to process a much greater amount of the raw sensory
data, even if it is sometimes more unstructured and difficult to focus
on just one thing.

9. VISIONS FROM BEYOND
• Yet another experience common to psychedelic experiences is that of ‘receiving
visions’. These are often taken as mystical revelation from another realm or world
by traditional shamanic use of psychedelics in their rituals.
• In contrast to the visual distortions, these visions are not generated on the visual
cortex. They are more in line with dreaming whilst awake.
• Disrupting connectivity of the posterior cingulate cortex (PCC) through electrical
stimulation causing ‘waking dreams’ not dissimilar to that aspect of the
psychedelic state. PCC cerebral blood flow is lower during REM sleep, and as a
direct result of tryptamine psychedelics, showing a likely cause of these same
effects when taking a psychedelic[vii].

10. ONENESS WITH THE UNIVERSE
• Another common reported experience with psychedelic substances is that of undergoing a mystical
experience. The person experiences a sense of “oneness with the universe”.
• Additionally, at varying doses, users may report feeling they “can’t tell where my hand ends and an object
begins” or “melting in to the floor/furniture”.
• Beyond the role of the PCC described for dreams and dream-like visions, it is also an
important ‘hub’ of information transfer. One aspect of this is separation of the self and
the external world. It occurs as a part of a network based on asynchronous activity
with other areas of the brain – the “default mode network” (DMN). When this is
disrupted, the experiences described are the conscious mind’s attempt to make sense
of the situation[viii].
• At high doses (or moderate doses for someone ‘susceptible’), the person may even
have a complete ‘ego loss’ experience, where the sense of self is entirely gone and
they describe it (later of course) as “pure experience”.
• This can be interpreted as a complete breakdown of the DMN, so that the ‘self’ no longer exists until function is
regained.

11. IS THIS MEDICALLY USEFUL?
• Yes.
• Psychedelics hold a lot of promise for psychotherapeutic use, by ‘opening’ the
patient to examine repressed memories, and disassociate negative emotional ties
from the events in their past. Accordingly, there is strong potential for their use in
treatment of post traumatic stress disorder (PTSD), end of life anxiety, some kinds of
depression, and so on.
• More controversially, there is also potential use of psychedelics as a ‘one shot’ – or
‘infrequent’ – nootropic (drug for mental improvement in healthy people), by
helping people to discover more about themselves to improve their daily lives[ix].
• Psychedelic drugs have been used successfully for treating alcoholism[x], PTSD[xi],
and end of life anxiety[xii].

12. POTENTIAL DANGERS AND RISKS
• As with any drug, there are potential dangers and risks associated with tryptamine
psychedelics.
• Psychedelic tryptamines are as a general rule, not neurotoxic. There are some with
levels of neurotoxicity, however the most common ‘recreational’ psychedelics such as
LSD and psilocybin have been shown to be non-neurotoxic. This is in contrast to the
phenethylamine psychedelics (mescaline, 25-I-NBOMe, MDMA[xiii], etc.), which as a
‘general rule’ have some level of neurotoxicity associated with them.
• Additionally, psychedelics are also – as a general rule – non-addictive. Addictive drugs
generally either affect the reward pathways (dopamine based) or provide
an extremely uncomfortable withdrawal after having modified the user’s brain
chemistry. Neither of these are true of psychedelics in general, and especially not of
the tryptamine class.
• The largest risk associated with tryptamine psychedelics is an environmental risk rather
than a direct drug effect. When a person takes a psychedelic, they may become
unable to correctly judge dangers in their environments. As long as the psychedelic is
used in a medically controlled or otherwise ‘safe’ environment, the risk is extremely
minimal.

13. REFERENCES / NOTES
i. LSD is a non-typical tryptamine in that it has a tryptamine backbone, but a moderately complex structure aside that is not common amongst tryptamines. It is
therefore often classed separately as an ergoline; however these could be said to be a subclass of tryptamines.
ii. http://www.etymonline.com/index.php?term=psychedelic
iii. Dr David Nichols, presentation shown at Psychedelic Science 2013
https://www.youtube.com/watch?v=LbUGRcuA16E
iv. J.B. Blair et al. Effect of Ring Fluorination on the Pharmacology of Hallucinogenic Tryptamines. J Med Chem. 2000 Nov 30;43(24):4701-10
v. Geometric visual hallucinations, Euclidean symmetry and the functional architecture of striate cortex. Phil. Trans. R. Soc. Lond. B March 29, 2001 356 1407 299-330;
1471-2970.
vi. P Bressloff et al. What Geometric Visual Hallucinations Tell Us about the Visual Cortex. Neural Computation 14, 473–491 (2002) Massachusetts Institute of Technology.
http://www.math.utah.edu/~bresslof/publications/01-3.pdf
vii. Herbet, G., Lafargue et al. A commentary on disrupting posterior cingulate connectivity disconnects consciousness from the external environment. Neuropsychologia
56C, 239–244. doi: 10.1016/j.neuropsychologia.2014.01.020.
http://journal.frontiersin.org/Journal/10.3389/fpsyg.2014.00255/full
viii. Dr Robin Carhart Harris: Psilocybin and the Psychedelic State.
https://www.youtube.com/watch?v=G8Yu64Q7JgI
ix. D Bewan (2013). Dropping Acid: A Beginner’s Guide to the Responsible Use of LSD for Self-Discovery.
http://www.amazon.com/Dropping-Acid-Dale-Bewan/dp/1492318191/
x. J Ross MacLean et al. The Use of LSD-25 in the Treatment of Alcoholism and Other Psychiatric Problems. Quart.J.Stud.Alcohol. 1961 March;22:34-45.
xi. Amber Lyon. How Psychedelics Saved My Life.
http://reset.me/story/howpsychedelicssavedmylife/
xii. P Gasser et al. Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. J Nerv Ment Dis. 2014
Mar 3.
http://www.maps.org/research/lsd/Gasser-2014-JMND-4March14.pdf
xiii. Methylenedioxymethamphetmine, better known as MDMA, is only sometimes grouped in with more traditional psychedelics and is often classed separately as an
entactogen/empathogen instead due to the vastly different subjective effects.

14. HOW THE COURSE HAS HELPED
• In order to fulfil the project requirements, this slide covers my own thoughts as to how the course has helped me better
analyse the events and phenomena around me. It is not related to the rest of the slides.
• “Understanding the Brain: the Neurobiology of Everyday Life” has made me much
more aware of:
• The many basic activities that my brain and body are performing autonomously:
• After the Week 5 and 6 lectures, I am more aware of the sights and sounds around
me and how my brain may play tricks on me in perceiving them.
• After the Week 7 lectures, I found myself trying to be consciously aware of my own
postural sway.
• Paying more attention to other people’s behaviours:
• Looking at people’s eyes for evidence of neurological problems (thankfully, I haven’t
seen any!)