The trap bar deadlift

The conventional deadlift is done using a standard 20 kg barbell in powerlifting. Trap bars have a hexagonal shape which you stand in (which is why they’re sometimes called “hex bars”) with sleeves on the end that let you load weight, and they have handles on either side that allow you to grip the bar with a neutral grip.

During my 8-week wave cycling program for the squat, I had also been using the trap bar to do some deadlifting once a week during the last half of the program. Prior to that, I was doing Romanian deadlifts at about 60% of my conventional deadlift 1 rep max to work on improving hamstring strength. After I tested my squat 1-rep max, I also decided to see whether I could lift more than my current 1 rep max of 210 kg. The video below shows me setting a new personal best at 220 kg, and I felt I still had a little more in the tank.

From my experience using the trap bar, I assume I can usually lift around 20-30 kg more on the trap bar than in the conventional deadlift using an Olympic bar. I was curious to see what the typical difference was and did some searching on the web. I came across Greg Nuckold’s very detailed review of the relative benefits of trap bar deadlift versus conventional deadlift (CDL) on his Strength by Science website.  Originally sceptical of the value of the trap bar lift, Greg was convinced by the studies he reviewed that the trap bar lift was actually a better training option for people who are not wanting to compete in powerlifting, where the conventional deadlift is mandatory.  He reviewed a number of studies and concluded that “the trap bar deadlift works your back and hip extensors almost as hard as the conventional deadlift does at worst, and just as hard in all likelihood, with the added benefit of also providing a little extra stimulus for your quads (though not nearly as much as squatting does).”

In particular, he examined two studies which assessed the difference in 1 rep max lifts for conventional and trapbar deadlift. For the study in which the lower trapbar grip was used (in line with the central axis of the weights), on average the study subjects could lift 8.4% more with the trap bar than the conventional deadlift.

The study that explicitly compared the high-handle trapbar lift with the conventional lift had a difference of 14.9 %. That would imply that my 220 kg high-handle trapbar lift would correspond to a conventional deadlift of 191.5 kg, very close to my previous personal best of 190 kg set pre-pandemic in 2019.  I felt I was not quite at my absolute max when I lifted 220, so possibly my conventional deadlift has improved a little over the pandemic, though I have not been training it intensively. If I can get to a conventional deadlift of 200 kg soon, that would put me within 20 kg of the current drug-free European record for my age-weight class.

Definitions of God and the Motte-and-Bailey fallacy

Recently, I got involved in an online discussion about whether spirituality was compatible with atheism (see previous post Atheism and Spirituality) and foolishly did not clarify what the term “god” referred to. But it was clear from the general context that those arguing atheism was incompatible with spirituality were assuming spirituality required belief in God and were using a concept of God (singular) largely consistent with the standard Christian God who is conceived of as an eternal being who created the universe and life, and who is both transcendent (wholly independent of the material universe) and involved in the world.

In particular, most Christians seem to believe that God has laid down a set of moral rules to be followed, although they often disagree on what these are. God is usually conceived of as omnipotent and omniscient. Christians with modern religious values tend to see God as loving and benevolent, whereas those with pre-modern values tend to see God as someone who is jealous, to be feared and who punishes those who don’t follow his rules or worship him. Above all, the monotheistic God(s) are mostly seen by their followers as personal Gods. In contrast, many theologians and philosophers have conceptualized God as impersonal, not involved with material creation, or as congruent with the universe (pantheism) or with the Ground of Being.

In the online discussion I said:

“The complete lack of evidence for any god-like interference in the activities of the small corner of the universe I live in, or in the broader dynamics of the universe that can be detected from earth, is sufficient evidence for the lack of existence of the specific entities mentioned in major world religions. Silly attempts to redefine these entities as entirely different entities that are undetectable by humans or don’t have any interaction with humans can safely be ignored, as such entities have no relevance to either the claims of these religions or to my life.”

I received an angry reply from someone who accused me of insulting her by assuming she had a primitive conception of God, and I needed to educate myself about the true nature of God, as the ground and source of being. My reply:

“If you want to redefine your god as either “the ground of being” or “instant coffee granules” I am happy to believe your particular god exists, but I will immediately discount any and all claims that instant coffee granules care about sexual behaviour, orientation or reproductive choices, or a whole host of other issues.”

In the last few days, I came across a discussion of “God as the ground of being” which much better expressed my gut reaction that such definitions of God mean that the question of whether God exists becomes a nonsensical question. If God is equated with reality, the only question becomes “What is the nature of reality?” And in fact that is not what the vast majority of God believers actually mean by God and their belief in God.

Alex SL commented on the Crooked Timbers blog that the redefinition of God as the ground of being was a motte and bailey fallacy. This is a fallacy where an arguer conflates two positions which share some similarity. The motte position is easy to defend, but the bailey position is much more controversial. The arguer can claim that the bailey has not been refuted, because the critic refused to attack the motte. Alex SL illustrates how the redefinition of God is an example of this fallacy as follows:

Community worships a bearded guy on a cloud who helps them win football games and cures diseases if they pray enough. Sophisticated theologian ™ looks on, doesn’t correct them.
Atheist walks past and has a giggle.
Sophisticated theologian steps in and says, “you foolish, boorish atheist, you misunderstand completely how our religion works; we believe in an impersonal ground of being, nothing more.”
Atheist walks off.
Community goes back to praying to bearded man on cloud for personal health and fortune, uses holy book to justify bigotry against minorities, etc. Sophisticated theologian looks on, doesn’t correct them.

The redefinition of God (the motte) becomes defensible and difficult to refute to exactly the degree it then becomes meaningless and not what the vast majority of people understand the term god to mean, in other words it is not what any real-life discussion or concerns such as “will I persist after biological death” or “will god punish us if we don’t kill the heretics in our midst” are about (the bailey).

Improving my squat using wave cycling

After a week skiing in February 2015, my knees became inflamed and painful and I had trouble walking up and down stairs. I found that deadlifts improved my knee function and started powerlifting training for deadlifts and bench press. For the first months, I avoided the squat completely, and only gradually started to squat with relatively light weights around 50-60 kg. In the last couple of years, I’ve discovered that my knees are fine with squatting with good technique to parallel or below. I still have trouble getting below parallel with heavy weight on the back but am working on improving mobility. In my last pre-pandemic competition in December 2019, I squatted 107.5 kg with depth that was only just below parallel and one of the judges told me afterwards he thought they had been lenient in judging depth. This was substantially behind my deadlift at 190 kg. Most powerlifters have squat somewhat less than they can powerlift, but the difference is on average only around 20% and is narrower at 15% at the elite level (see here for averages based on over 7 million lifts).

So I decided to focus over the last 8 weeks on improving my squat, to do only a minimal amount of deadlifting, and no bench press (instead to rehabilitate an AC joint injury). I had been reading Pavel Tsatsouline’s book Beyond Bodybuilding: Muscle and Strength Training Secrets for The Renaissance Man and decided to do the 8 week wave cycling program that he describes on page 80 of the Kindle edition.  Here is how it worked for my squat:

I assumed my squat one rep max was currently 110 kg and my best working weight for 5-rep sets was 90 kg. For the first week, on Monday I performed 90×5, 92.5×4, 95×3, 97.5×2, 100×1. Following Pavel’s recommendation, I rested for 3 minutes between the sets. On Wednesday, I added 2.5 kg to all my sets: 92.5×5, 95×4, 97.5×3, 100×2, 102.5×1. On Friday, I added another 2.5: 95×5, 97.5×4, 100×3, 102.5×2, 105×1. Each new week, on Monday, I backed up to my last Wednesday numbers and worked back up. So every week, I added 7.5 kg to my sets and then took 5 kg off and built up again. This is why it is called ‘wave cycling’. Looking just at the singles, my weeks looked like this: 100, 102.5, 105; 102.5, 105, 107.5; 105, 107.5, 110, etc.

At the end of the 8th week, my last single was at 117.5 kg.  I then tested my 1 rep max at 120 kg (shown in video below). I felt like I could probably have added a little more, but as my depth was still problematic, decided not to. The video shows that I am getting to parallel or very fractionally below it, and I need to do more work to get consistently below parallel. So that will be my focus for the next weeks.

Atheism and Spirituality

Late last year I volunteered to participate in a research study on psilocybin-occasioned mystical experiences.  I completed an online survey and later was interviewed by the principal researcher in a more than hour long semi-structured zoom interview. In the survey, I had answered a question on religious affiliation with “Atheist”. During the interview, the interviewer expressed surprise that I practiced Zen meditation as she equated atheism with a materialist philosophy.  I in turn was surprised at her assuming that a spiritual practice implied a belief in God or gods, particularly as my practice was to a large extent within a Zen Buddhist context, which does not treat the historical Buddha as a god or invoke concepts of gods.

I refined my thoughts on this topic in several online discussions, where I found both religious believers and some other atheists were very hostile to the idea that an atheist could have a spiritual practice. And I noticed that some of the atheists who did say they were spiritual, defined “spiritual” in terms of experiences like the enjoyment of a sunset or a moving piece of music, or the feeling of being part of nature.  

In the last few days, I have read Sam Harris’s 2014 book, Waking Up: Searching for spirituality without religion and found he articulated far better than me almost the same views that I had arrived at. Like me, he noted that when he refers to meditation as a “spiritual practice,” he gets substantial criticism from fellow skeptics and atheists who think that he has committed a grievous error.  To many of these people, the word spiritualism has become synonymous with premodern superstitions and beliefs, particularly in supernatural beings.

Harris explains that he does not share their semantic concerns:

“there is no other term — apart from the even more problematic mystical or the more restrictive contemplative  —  with which to discuss the efforts people make, through meditation, psychedelics, or other means, to fully bring their minds into the present or to induce non-ordinary states of consciousness. And no other word links this spectrum of experience to our ethical lives.”

Those who do try to embrace both science and spirituality tend to make one of two mistakes. Scientists and some atheists assume that spiritual experience equates to “a grandiose way of describing ordinary states of mind- parental love, artistic inspiration, or at the beauty of the night sky”. For example, Einstein’s awe at the order in nature captured in its physical laws is often described as though it were some sort of mystical insight.

In contrast, new age thinkers like Fritjof Capra and Deepak Chopra tend to draw connections between altered states of consciousness and the strange reality uncovered at the frontier of modern physics by theories such as quantum physics, relativity, string theory. These scientific theories and their interpretations are claimed to validate and justify various metaphysical claims. As Harris summarizes, “in the end, we are left to choose between pseudo-spirituality and pseudo-science.”

Few scientists and philosophers have developed strong skills of introspection – of disciplined close examination of their own consciousness through meditative and related practices. But various Eastern religious and philosophic traditions have developed sophisticated techniques for exploring the first-person experience of consciousness. As Ken Wilber has pointed out in a number of books, particularly The Marriage of Sense and Soul: Integrating Science and Religion, at the heart of these traditions is a set of instructions to examine consciousness for yourself and empirically test the truth of claims made. Of course, these traditions have often developed an accretion of mythic and cultural interpretations. And although these meditative techniques tell us nothing about the structure of the universe, or its origins, or the existence of meta-beings, they do confirm various truths about the human mind and consciousness, particularly that our conventional sense of self is an illusion, and that our thoughts play an important role in how we experience reality. See also my earlier post on secular Buddhism.

The experience of “no-self” is accessible in principle to anyone prepared to honestly do the work with an open mind. It is often interpreted in religious terms and in terms of established mythical religious systems, but in principle there is nothing irrational about it.  People of every tradition have the same sorts of spiritual experiences and again Wilber has been a indefatigable cataloger of these commonalities across “mystic” traditions within every religion. He and Alan Coomes have also elucidated how no-self and non-dual states of consciousness are interpreted and reported in terms of the overall stage of consciousness of the experiencer and the cultural and religious context in which they live. Christians, Muslims, Hindus, atheists, Buddhists and psychedelic voyagers can all experience “enlightenment”, no-self, universal love, ecstasy etc, and often interpret them in terms of and as support for their traditional beliefs. But these beliefs are incompatible, so the actual experiences must be pointing to some deeper and singular reality.

Sam Harris describes the subject of his book as an examination of the experience of “no-self” as a clearer understanding of the way things are:

“Deepening that understanding, and repeatedly cutting through the illusion of the self, is what is meant by “spirituality” in the context of this book…….. a true spiritual practitioner is someone who has discovered that it is possible to be at ease in the world for no reason, if only for a few moments at a time, and that such ease is synonymous with transcending the apparent boundaries of the self. Those who have never tasted such peace of mind might view these assertions as highly suspect. Nevertheless, it is a fact that a condition of selfless well-being is there to be glimpsed in each moment.”

Harris argues, as I do, that all religions and spiritual practices are addressing the same reality and that any view of consciousness and the cosmos that is available to the human mind can, in principle, be appreciated by anyone.  Wilber has used this same insight to argue that because all religions are products of human minds grappling with the same reality, the nature of that reality can only be described by those components of religious thought or experience that are common to all religions. So mythic accretions cannot be literal truths about reality, though they may well address in metaphorical terms fundamental aspects of human psychology and existence. Additionally, not all religious traditions understand our spiritual potential equally well, or encourage spiritual growth or provide effective tools for exploring it. In fact, mystics in the monotheistic religions have tended to be labeled heretics and persecuted or killed. And this is not confined to earlier less enlightened times, it continues today.

Harris has a more intensive background in meditative disciplines than I do. His are mainly in the Theravada and Tibetan Buddhist traditions. He was fortunate to meet and practice with a Vipassana master in the Theravada tradition and a Dzogchen Tibertan master who were both exceptionally skilled in guiding students effectively with minimal demand to take on the mythic religiosity of either tradition.  I also found two Zen teachers, one Australian and the other Japanese, who were similarly focused on effective practice and realization with minimal need to take on Buddhist religiosity. In my encounters with both Theravada and Tibetan Buddhist teachers I found more emphasis on Buddhist beliefs and dogmas than I was comfortable with. So these disciplines with typical South Asian elaborate metaphysical systems have never appealed to me the way Zen does with its emphasis on direct experience here-now.

Like Harris, I see my meditation practice as spiritual practice and am not shy about seeing that as completely consistent with atheism.  To those that say atheism implies materialism, I would respond that thoughts and consciousness are not material, but they exist and in fact I have more direct and irrefutable experience of them than of material objects (perhaps I am only a brain in a vat). Whether or not thoughts and awareness itself are emergent properties of complex material systems such as the human brain is not relevant, they themselves are not material. Unlike those who equate spiritual with supernatural, I do not consider anything that is real to be supernatural. I realize that is not how others may understand the term, but to me the word supernatural is equivalent to non-existent.

In the Zen tradition, there are a number of words used to refer to various states of consciousness. These include samadhi, kensho and satori and these may be used in various ways. I use samadhi to refer to the meditative state of resting as the witness, as conscious awareness in which perceptions and thoughts come and go and are simply witnessed without getting caught up in them.  In lengthy periods of samadhi, awareness of the body and of time passing can drop away. One is largely resting in the present moment here-now. It can often feel very blissful.

Kensho refers to the state in which the witness also drops away. The witness disappears- there is no body, no mind, no self, no other, no subject, no object. Not even the object of your attention exists. This is a state of non-dual consciousness, also referred to in Zen as “body and mind dropped away”. Kensho can be a small glimpse or opening, or a somewhat larger taste of non-dual consciousness. A profound kensho is referred to as satori, the classical enlightenment experience of the type described in many tales of historical Zen masters. The 13th century Zen master Dogen Zenji described Buddhist practice in the following famous quotation:

To study the Buddha way is to study the self.
To study the self is to forget the self,
and to forget the self is to be enlightened by the 10,000 things.
To be confirmed by the 10,000 things is the dropping away of body and mind,
and the body and mind of others.
No trace of realization remains, and this no-trace continues endlessly

Returning to the question of spirituality, I would  define it as follows. Human beings consist of body, mind and spirit. Body is fairly self-explanatory, and mind refers to perceptions, thoughts, feelings and normal conscious awareness. Spirit refers to what remains when body and mind are dropped away. From direct experience I know that what is left (non-dual consciousness) is something, not nothing, and that something can be a life-changing experience. I will let Harris have the last word:

“Investigating the nature of consciousness itself- and transforming its contents through deliberate training- is the basis of spiritual life…. having done so, we will say that spirituality is not just important for living a good life; It is actually essential for understanding the human mind.”

Zazen, left brain, right brain, self

During the last COVID wave, while activities were restricted and I was largely staying at home, I intensified my zazen (sitting meditation) practice. With more attention to my  practice, I was surprised to find I was easily sitting for 45 minutes and spending less of that time lost in thoughts and more time simply being present here-now aware of the arising and passing on random thoughts, sensations and sensory inputs.

There are four main categories of things that distract my attention from being here-now:

  • Largely verbalised thought sequences. These can be somewhat spontaneous, jumping across subjects and concerns, or more focused on solving a problem, thinking through a situation or piece of work to be done, planning, strategizing, worrying, pondering the past or future.
  • Distracting sensory stimuli with associated thoughts and emotions, eg. An intrusive noise, an insect flying around or crawling on my skin, an itch, or an ache or pain.
  • Images that appear in the minds eye. These can be random or connected.
  • Full-blown dream-like visions or daydreams, sometimes short, sometimes long.

I also occasionally experience auditory or olfactory hallucinations. For example, a voice saying something, or a distinct smell.  But these are rare.

I’ve been paying attention to these distractors, the so-called monkey mind, and getting better at observing them arise and letting them go, rather than being mindlessly caught up in them, and discovering some minutes later that I have been completely lost in a train of thought or a daydream. And I have increasing periods when I am sitting in awareness here-now, without thoughts or other types of mental distractions. My attention may be on the breath (sensation, following, counting), or on a koan key word, or simply on what is arising in consciousness (shikantaza).

In the last week or so, I have become aware from time to time that hidden in my awareness there is a non-verbal though process going on. Because it does not involve conceptual thinking or quasi-verbal expression, it is difficult to notice. But I have realized that there is a part of me still thinking in some sense in a non-verbal way. This tends to be about some sort of witnessing by my observing awareness and a judging process about the extent to which I am present “here-now”. I tentatively concluded that my monkey mind was very very clever, and was trying to get around my practice of letting go of thoughts (those largely verbalized or visual sequences) by finding a much less obvious way to think non-verbally. But then I came across another possibility.

Last night I was reading about the split-brain research of Roger Sperry and others nearly 50 years ago, resulting in Sperry receiving the 1981 Nobel Prize for Medicine. The human brain consists of two hemispheres connected by several neural networks, the main one being the corpus callosum. In patients whose corpus callosum had been surgically cut in half (to prevent epilepsy) the two hemispheres had little communication and function largely independently. In particular, in most people, the left hemisphere is largely responsible for verbal communication, and the right more dominant in reading and displaying emotions, and in spatial and musical processing. For a fascinating and more detailed summary of this research, see Sam Harris’s 2014 book Waking Up (highly recommended). In particular, he explains why this research leads to the conclusion that the two hemispheres of the split brain are independently conscious.

A key experiment involved flashing a word, say “Egg”, to the left half of the visual field, processed by the non-verbal right brain, and the subject (speaking from the language-dominant left brain) will say they saw nothing. When asked to reach behind a partition and select an object with his left hand (controlled by the right brain), he will select the egg. Ask him to name the object he now holds in his left hand without allowing the left brain to get a look at it, and he will be unable to reply. The right brain is “thinking” and it knows that it saw the word egg and can recognize the feel of an egg and select it, but does not have the words to express that.

Is it possible that the time spent training my consciousness to let go of thought trains has enabled me to develop the skill of doing so for left-brain verbal thought trains, but not so much for the right brain’s non-verbal thinking?  Its quite exciting to think I may actually be noticing the much more subtle non-verbal thinking of the right brain, usually well and truly overspoken by my quite strongly developed verbal-cognitive thought processes. These have been quite strongly developed by a career focused on mathematical and statistical modelling, where I’ve learnt to play out quite complex analytic processes in my head before implementing them in a computer program or spreadsheet.  I’m not too much of a mansplainer I hope, but definitely a left-brain-splainer. 

In any case, I am now also paying attention to these more subtle thoughts arising, and seeking to let them go the same way I have been letting go of the more verbal or visual thought trains. But I wonder whether the left-brain chatter and the more subtle right-brain awareness are disengaging while I sit zazen, and perhaps becoming two somewhat more separated selves, or perhaps no self at all.

Neurotransmitters and brain function

Although I’ve taken a general interest in brain function and states of consciousness, until the last few years I really only paid much attention to the relationship between brain waves and states of consciousness, and in particular the use of brainwave entrainment methods to facilitate certain states (see earlier post here). Only in the last few years have I looked more closely into the complex and interacting roles of brain waves, neurotransmitters and various brain networks.

By Thomas Splettstoesser (www.scistyle.com), https://commons.wikimedia.org/w/index.php?curid=41349083

Neurons (nerve cells) in the brain form elaborate networks, with each neuron having up to 15,000 connections with neighbouring neurons at contact points called synapses. While the nerve impulse travel through the neuron as an electrical impulse, it does not cross the gap known as the synaptic cleft but rather stimulates the release of a chemical messenger: a neurotransmitter. This crosses the synaptic cleft and is received by neurotransmitter receptors on the target cell. A neurotransmitter with increase (excitatory) or decrease (inhibitory) the probability that the target cell will produce a nerve impulse.

There are three main types of neurotransmitters in the brain: small molecules used for fast signal transmission between neurons, small used for slower modulation of network activity, and large molecules (peptides) used for even slower modulation of cell circuit functions. Most neurons have receptors for most of the neurotransmitters in all three of these categories.

The two main fast acting signal transmission neurotransmitters are the amino acids glutamate and gamma-Aminobutyric acid (GABA). 99% of all neurons in the brain release one of these two chemicals. All the major functions of the brain, including perception, cognition and consciousness involve neurons communicating using these two neurotransmitters.

The neuromodulators are small molecules including acetylcholine and the monoamines dopamine, serotonin and norepinephrine. The neuromodulators account for less than 1% of neurons, but play an important role in activating widespread neural systems or networks that play an important role in emotions, behaviour and other functions (see below).  

The circuit modulation neurotransmitters are peptides (large protein molecules) used for slower modulation of neural functions and include endorphins, cannabinoids, oxytocin and many others.

In this post, I have tried to make a succinct and inevitably simplistic summary and overview of the more important neurotransmitters below, focusing mainly on brain function (not functions in other parts of the nervous system and body).

Glutamate

Glutamate is an amino acid that is the major excitatory neurotransmitter in mammalian central nervous systems. Glutamate is probably best known as “monosodium glutamate” or “MSG” which is the sodium salt of glutamic acid and a white crystalline solid used as a flavor or taste enhancer in food (food additive number E620). The taste of glutamate is described using the Japanese word “umami” which has not English equivalent (roughly corresponds to “savoury”). People taste umami through taste receptors that respond to glutamate. Umami is recognized as one of the five basic tastes as it is detected through its own specific receptors, rather than arising from a combination of taste receptors. The other basic tastes are salty, sweet, bitter, and sour.  

Glutamate has excitatory effects on nerve cells, and that it can excite cells to their death in a process now referred to as “excitotoxicity”. Powerful uptake systems (glutamate transporters) prevent excessive activation of these receptors by continuously removing glutamate from the extracellular fluid in the brain. Additionally, the blood–brain barrier shields the brain from glutamate in the blood.

Glutamate excitotoxicity is believed to be involved in some degenerative brain diseases such as Alzheimer’s disease2 and amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease, the disease that Stephen Hawking had.) In ALS, there are decreased levels of the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity which affects motor neurons to a greater degree than other types of neurons. The first and so far only approved specific treatment for ALS is riluzole, a drug that modulates glutamate. Glutamate deficiency is associated with insomnia, concentration problems, mental exhaustion and ADHD-like symptoms. PCP and ketamine decrease or block glutamate.

Gamma-aminobutyric acid (GABA)

Gamma-aminobutyric acid or GABA is the chief inhibitory neurotransmitter and is used at the great majority of fast inhibitory synapses in virtually every part of the brain. GABA is primarily synthesized from glutamate via the enzyme glutamate decarboxylase (GAD) with pyridoxal phosphate (the active form of vitamin B6) as a cofactor. This process converts glutamate (the principal excitatory neurotransmitter) into GABA (the principal inhibitory neurotransmitter). GABA largely does not cross the blood-brain barrier.

Although it has depressive effects on the central nervous system, the subjective effects of GABA are the total opposite. GABA helps the mind and body to relax, and it is known to help counter the effects of stress. It also helps to regulate sleep and mood. Sedatives/tranquilizers, general anesthesia, and anti-seizure drugs work by enhancing GABA, which suppresses brain activity. Alcohol, barbiturates (phenobarbital), benzodiazapines (valium), GHB all mimic or increase the effect of GABA. GHB is a precursor to GABA in certain brain areas.  Phenibut (available as a nutritional supplement in some countries) is a central nervous system depressant that is a GABA analogue and acts as a GABAB receptor agonist (an agonist is a chemical that binds to a receptor and activates it).

Acetylcholine (ACh)

Acetylcholine is the transmitter used at neuromuscular synapses (junctions): motor neurons release this to activate muscles. It is also used in the autonomic nervous system, being the internal transmitter in the sympathetic nervous system and the primary transmitter of the parasympathetic nervous system. In the brain, it acts both as a transmitter and a neuromodulator. The brain contains a number of cholinergic areas that play important roles in arousal, attention, memory and motivation

ACh an ester of acetic acid and choline. It is synthesized from choline by the enzyme choline acetyltransferase, and is metabolized by acetylcholinesterase, an enzyme that is present in the postsynaptic membrane. ACh cannot cross the blood-brain barrier and is synthesised in brain neurons from choline, which does cross the barrier. Choline can be synthesised by the human body, but must be supplemented from food sources. It is found in meat, vegetables and fruit, but is particularly high in organ meats and egg yolks.

ACh plays an important role in alertness, attention, learning and memory. It also promotes REM sleep. Damage to the ACh-producing system in the brain has been shown to be associated with Alzheimer’s disease. Nicotine activates the ACh receptors. As do nerve gases (VX, Sarin). Drugs that decrease or block acetylcholine include atropine, scopolamine, curare, botox.

Dopamine

Dopamine (DA or 3,4-dihydroxyphenethylamine) is a monoamine neurotransmitter which plays a significant role in motivation and reward-motivated behaviour and learning, mood, pain and appetite. It has both inhibitory and excitatory functions.

Dopamine is incapable of crossing the blood-brain barrier and must be synthesised in inside the brain. Its direct precursor L-DOPA is synthesised in the brain and kidneys from either the essential amino acid phenylalanine or the non-essential amino acid L-tyrosine, both of which are found in nearly every protein in food.

Seppi333, Hbf878, CC BY-SA 3.0 , via Wikimedia

All dopamine-containing neurons exist in cell groups in the midbrain (the substantia nigra and the ventral tegmental area). Parkinson’s disease results from the loss of dopamine-secreting cells in the substantia negra (a structure in the mid-brain that plays an important role in reward and movement). The most widely used treatment for parkinsonism is the use of L-DOPA, the metabolic precursor of dopamine. Unlike dopamine, L-DOPA can cross the blood-brain barrier.

Most antipsychotic drugs act as antagonists for the dopamine receptor (many for the D2 subtype). This led to the dopamine hypothesis that schizophrenia was due to hyperactivity of the brain dopamine systems. However, schizophrenia patients do not typically have elevated levels of dopamine and it is now thought that schizophrenia symptoms result from dysregulation of the dopamine receptors in the brain, particularly overactivation of the D2 receptor. Haloperidol (Haldol) is a typical antipsychotic used for the treatment of schizophrenia, Tourette syndrome and various psychoses. It is a dopamine antagonist that binds to the D2 receptor and also to the serotonin 5-HT2 receptors at a higher dose.

The mesolimbic pathway, sometimes referred to as the reward pathway, is a dopaminergic pathway in the brain that connects the ventral tegmental area in the midbrain to a part of the forebrain that includes the nucleus accumbens. The release of dopamine from the mesolimbic pathway into the nucleus accumbens regulates the motivation and desire for rewarding stimuli and reward-related learning. It may also play a role in the perception of pleasure. The dysregulation of the mesolimbic pathway by addictive drugs plays a significant role in the development and maintenance of an addiction. Addictive substances such as cocaine, alcohol, and nicotine increase extracellular levels of dopamine within the mesolimbic pathway, particularly within the nucleus accumbens. This results in the perception of reward and increased motivation to repeat the behaviour that caused it.

Altered dopamine neurotransmission is implicated in attention deficit hyperactivity disorder (ADHD). The psychostimulants used to treat ADHD (such as Ritalin or Adderall) increase both dopamine and norepinephrine levels in the brain. Wellbutrin is a norepinephrine-dopamine reuptake inhibitor that is used to treat depression.

Serotonin

Serotonin (or 5-hydroxytryptamine (5-HT)) is a monoamine neurotransmitter and neuromodulator  produced in the gastrointestinal nervous system and the brainstem. It has both inhibitory and excitatory functions and plays a significant role in the sleep/wake cycle, mood, pain and appetite. Serotonin deficiency is associated with depression and anxiety. Most antidepressants act on serotonin, and sometimes also on norepinephrine.

NEUROtiker, CC BY-SA 3.0 , via Wikimedia Commons

Serotonin deficiency leads to depression and/or anxiety. Excess serotonin results in increased relaxation, decreased libido, increased non-REM sleep, suppressed REM sleep, and high levels can cause serotonin syndrome (which can be fatal).

Serotonin does not cross the blood-brain barrier but its precursors do:
Tryptophan –> 5-Hydroxytryptophan (5-HTP) –> Serotonin –> Melatonin

Serotonin levels can also be raised by taking selective serotonin reuptake inhibitor drugs (SSRI) such as Zoloft (sertraline) and citalopram. Tricyclic antidepressants also block the reuptake of serotonin and norepinephrine. Amphetamines such as MDMA (ecstasy), MDA, MDEA, act as serotonin-norepinophrine-dopamine releasing agents and are also agonists for the serotonin 5-HT2B receptor. Cocaine, LSD and other psychedelics also interact with serotonin receptors, as well as dopamine and other receptors.

Norepinephrine

Norepinephrine (also called noradrenaline) is a monoamine neurotransmitter in both the peripheral and central nervous systems. It is synthesised mainly within the neurotransmitter vesicles from dopamine (see diagram earlier for the dopamine pathway).

It is the main neurotransmitter used by the sympathetic nervous system, where it can modify organs throughout the body to facilitate active body movement, often at the cost of increased energy use and wear and tear.  Norepinephrine in the brain is the neurotransmitter for the noadrenergic neurons whose activation results in alertness, arousal and readiness for action. The norepinephrine system is important in attention (alerting, focusing, orienting), appetitive behaviours, the hedonic (pleasurable) properties of natural and drug-related reinforcement, mood, and regulation of blood pressure.

ADHD drugs, cocaine, and amphetamines activate dopamine and norepinephrine receptors. Many drugs that inhibit the reuptake of norepinephrine into presynaptic terminals (tricyclic antidepressants such as desipramine) or the metabolism of norepinephrine in the presynaptic terminals (MAO inhibitors such as iproniazide) are used to treat clinical depression.

Epinephrine (Adrenaline)

Epinephrine (also known as adrenaline) is a monoamine hormone and neurotransmitter, which is synthesized from norepinephrine in the adrenal glands and by a small number of neurons in the medulla oblongata (in the lower brainstem). It plays an important role in the fight-or-flight response, a role in sleep, and with ones ability to stay or become alert. Adrenaline is a key factor in enabling the extreme muscle contraction involved in feats of extreme strength, often occurring in times of crisis. Eddie Hall has described how he used hypnosis to create what he called a “very dark mental scenario” which enabled him to summon the strength needed to become the first person ever to deadlift 500 kg.

Cannabinoids

Cannabinoid receptors were only discovered relatively recently in the 1980s. The two main cannabinoid receptors are termed CB1 and CB2. The endocannabinoid system uses endogenous cannabinoid neurotransmitters that bind to the cannabinoid receptors. This system regulates multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others. THC, the primary psychoactive component of the cannabis plant (marijuana, hasish) produces its effects by binding to the CB1 receptor in the brain.

Opioid peptides

This system consists of widely scattered neurons that produce three opioids: beta-endorphin, the met- and leu-enkephalins, and the dynorphins. These opioids act as neurotransmitters and neuromodulators at three major classes of receptors, termed mu, delta, and kappa, and produce analgesia. Opioid peptides have been reported to inhibit the release of acetylcholine, dopamine, and norepinephrine in both the brain and the peripheral nervous system. The addictive opiate drugs exert their effects primarily as functional analogs of opioid peptides, which, in turn, regulate levels of dopamine, and norepinephrine. In addition, opioid peptides can increase as well as decrease the release of serotonin and GABA in the brain. Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, and the control of food intake.

Endorphins are produced and stored in the pituitary gland and inhibit the communication of pain signals. Endorphins can also produce a feeling of euphoria very similar to that produced by other opioids. Runners high is due to the release of endorphins. I recall the first time I was shown how to correctly do a deadlift and proceeded to do multiple sets of heavy deadlifts. I was high on endorphins for several hours afterwards, and hooked on powerlifting.

Oxytocin

Oxytocin is a peptide hormone and neurotransmitter. It is normally produced in the hypothalamus and released by the posterior pituitary. As a hormone, it is involved in childbirth and breast-feeding. It is also associated with empathy, trust, sexual activity, and relationship-building. It is sometimes referred to as the “love hormone,” because levels of oxytocin increase during hugging and orgasm.

Its neurotransmitter actions in the central nervous system are mediated by specific oxytocin receptors. Its complex influence on behaviour includes not only prosocial effects facilitating trust and attachment between individuals, but it also modulates fear and anxiety, as well as mood more generally, as well as social behaviours such as empathy and generosity, and in-group versus out-group behaviour.

Melatonin

Melatonin is a monoamine hormone and neurotransmitter primarily released by the pineal gland at night, and plays a key role in synchronizing the circadian rhythm and control of the sleep–wake cycle. Melatonin is biosynthesised from serotonin as shown in the diagram below.

Creatine

Creatine is synthesized in the liver from the amino acids glycine and arginine, and stored in the major muscles. Once inside the muscle cells, creatine is phosphorylated to form creatine phosphate (CP), which, as a high energy substrate for the universal energy molecule adenosine triphosphate (ATP), assists in the contraction of the muscle fibers. Creatine phosphate is utilized to maintain higher levels of ATP during exercise. Creatine phosphate maximizes physical performance and reduces exercise fatigue by absorbing hydrogen ions released by muscles in the form of lactic acid.

Intense anaerobic exercise, such as weight lifting and sprinting, depletes ATP and greatly increases the demand for creatine. I take creatine as a supplement during powerlifting training cycles to facilitate training at higher volume and intensity. It is one of the few supplements for strength training with good evidence for effectiveness. Creatine crosses the blood-brain barrier and is also thought to enhance energy levels in the brain. There are several double-blind studies that suggest that creatine can enhance various cognitive skills. The evidence is complex (see here for a discussion). Perhaps the best study is an Australian study of 45 young adult vegetarian subjects followed for 18 weeks in a double-blind, placebo-controlled cross-over study. The level of creatine supplementation was 5 g per day, similar to level strength athletes supplement at.

The study results showed clear improvements on creatine supplementation in working memory and general intelligence. This is in line with results of previous studies showing that brain creatine levels correlate with improved recognition memory and reduce mental fatigue.

In conclusion

Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system affects large volumes of the brain, called volume transmission. Major neurotransmitter systems include the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system, and the cholinergic system, among others.  The brain, the volume transmission systems and the various brain-body networks have quite complex interconnections and feedback mechanisms.

A good example of this is stress. Most of the physiological effects of stress are regulated by the endocrine system, and in particular cortisol. The brain controls the endocrine system through the a circuit called the HPA axis (Hypothalamus-Pituitary-Adrenal). This allows the brain to recognize a threat and trigger the flight and fight response throughout the body.

However, those same hormones have a wide range of effects on the brain, altering brain function: including on the amygdala and hypothalamus, which are responsible for regulating stress to begin with (and do so in manners depending heavily on timescale, intensity, and a host of external factors). These sorts of feedback loops are common in the brain, so saying that one is cause and one is effect misses a lot of the complexity. Previous stress effects current neurotransmitter levels, which affects our current perception of stress and so on and so forth.

So, in summary, emotions and brain chemistry are interconnected to each other in complex and in many times inconsistent ways, depending on a wide range of other factors. Similarly, the relationship between neurotransmitters, brain waves and states of consciousness is also complex and cannot be reduced to a simple mechanistic cause and effect relationship. I will examine this further in a later post.

Spring in the time of coronavirus

Its been an odd spring in Geneva with days of sunshine interspersed between days of rain. After a slow start, 63% of the population have now received at least one dose of COVID19 vaccine (Pfizer or Moderna) and restrictions have been somewhat relaxed. People are now emerging from isolation and gathering together again in restaurants, bars and at the beaches around the lake. The bees are also out and about and I took a few photos of them in the backyard yesterday.

Why do Americans die earlier than Europeans?

A recent paper by demographers Sam Preston and Yana Vierboom showed that there are an additional 400,000 deaths in the USA in 2017 that would not have occurred it the USA experienced European death rates. That is about 12% of all American deaths and higher than the COVID-19 death toll of around  380,000 in 2020.  In a Guardian article earlier this month they identified major factors contributing to this US “mortality penalty” including overweight and obesity, drug overdose, lack of health insurance, suicide, lack of gun control and racism. These deaths tend to occur at younger ages than Covid deaths on average, so that total potential years of life lost are three times greater for the excess deaths than for Covid in 2020 (13 million versus 4.4 million).

Preston and Vierboom used data from the Human Mortality Database (HMD) for their analysis. They calculated death rates based on the five largest European countries, whose combined population size is very similar to that of the United States: Germany, England and Wales, France, Italy, and Spain. They also argued that using these larger European countries  to provide a mortality standard would avoid unrealistic expectations that might result from comparisons including small countries with possibly exceptional combinations of factors affecting mortality (e.g., climate, diet, social history, and healthcare delivery).

A few days ago, I downloaded updated data from the HMD and replicated and extended their analysis to include years up to and including 2020, drawing on recent data from Eurostat and national health statistics agencies (see here for details of data, sources and methods).

The figure above shows the ratio of US death rates to the average death rates for the five European countries (the “European standard”) by age, in 2000, 2010, 2019 and 2020. US mortality rates are consistently higher than the European standard for all ages below 80 years and the ratio has gotten progressively worse throughout the 21st century. The peak ratio for 25-29 year olds corresponds to death rates for US 25-29 year olds that are three times higher than those of the European standard.

The next figure shows the annual trend in total excess deaths in the USA above the number than would have occurred if the US population had been subject to the age-sex specific death rates of the European standard. This excess rose from 219,000 in the year 2000 to 410,000 in 2019 and 616,000 in 2020. Although there were over 380,000 Covid deaths in the USA in 2020, the European standard also includes substantial numbers of Covid deaths, and the Covid excess for the USA is “only” 136,000 deaths.

I next estimated the contribution of various factors to the US excess death rate using information on cause-specific deaths and death attributable to selected risk factors in Europe and the USA. I also made estimates of the excess deaths associated with lack of health insurance or under-insurance in the USA compared to Europe where all the countries have universal health insurance, based on a study of the death rates in the non-insured in the USA. Together, the six factors identified in the following graph account for around 80% of excess deaths in the USA. 

For 2020, the leading cause of excess deaths was overweight and obesity (around 154,000 deaths), followed by Covid-19 (136,000 deaths), drug use and overdose (103,000 deaths) and lack of health insurance (74,000 deaths). Excess deaths due to homicide and suicide were smaller at 20,200 and 11,200 respectively. If the USA had the European standard death rates for gun homicides and gun suicides, it would have 15,900 fewer gun homicides and 19,200 fewer gun suicides. Around 40% of the latter would still commit suicide by other means. The figure also illustrates the dramatic rise in drug overdose deaths, the vast majority due to opioids both prescription and illicit, which has occurred over the last decade. In a previous post, I examined this in more detail and noted that, in 2019, the USA accounted for an astonishing 40% of estimated global drug deaths.

Why does the US perform so poorly in these areas? Preston and Vierboom argue that a lack of federal oversight and regulation, powerful lobbying structures, deindustrialization of American jobs, and systemic racism combine to create “an annual tsunami” of excess deaths. And that is even without the complete mishandling of the response to Covid by the Trump administration and many state governments.