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Whole brain effects of tryptamine psychedelics

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

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Whole brain effects of tryptamine psychedelics

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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!)