Life is Chemistry
My quest to understand what makes us tick inevitably led me to a consideration of neuro-chemistry. Our bodies use chemicals to transmit the electrical signals that create both the objective and subjective state of affairs we call life. Reading up on this stuff is quite the eye opening experience. I remember my incredulity as a teenage boy on learning that there are receptors in the human brain that bind with compounds found in the Opium Poppy (Papaver Somniferum). Was this just a bizarre coincidence, or was there some ancient link (either evolutionary or designed) between plants and animals? It soon became clear that the Opium Poppy was just the tip of the ice berg. Many plants contain substances that perfectly compliment the complex structures embedded in cell membranes throughout our bodies. It is these synergistic relationships that enable the treatment of disease using herbal therapies.
Electrical signal transduction across the synapse
Our Addiction to Herbicides
One goal of The Science and Spirituality of Addiction (my forthcoming book) is to openly discuss situations where these plant-based therapeutics have hijacked their hosts and set them on a self-destructive journey that so often ends in death. The aim of this discussion is to get a better handle on why these things cause people so much trouble, and to explore why existing non-drug solutions are effective in addiction recovery. Why is it that belief in a higher power allows an individual to move away from their chemical dependency?
It’s true that many of the compounds abused by humans are made in the lab, but it would be rash of us to underestimate the creativity of nature in this sphere. While the stimulant drug Meth-Amphetamine was first synthesized by the Japanese in the 1930s, it has since been discovered occurring naturally in acacia trees native to Texas, along with its cousin Methyl-EneDioxy-Meth-Amphetamine (Ecstasy or MDMA). Most plant-based compounds which are psychoactive in humans are used by plants as a defense against herbivores, most notably insects. The best known member of this family is Nicotine, which has been used by gardeners as an insecticide for generations. High profile examples of the nicotine family include the Neo-Nicatinoid insecticides, which were recently banned by the European Union due to their devastating effects on bee colonies. How ironic that a compound (nicotine) used by the Nicotiana family as a defense against herbivores has become the most addictive drug known to man.
Stimulants and Depressants
All psychoactive chemicals interact, in some way, with neural membranes to modulate the frequency of electrical signalling either up or down. Sometimes this is done by binding with receptors that allow charged ions to move into or out of the neuron. In this case, positively charged ions promote electrical activity and negatively charged ions suppress it. At other times they might block or open ion channels (receptor-like structures) with the same effect, or cause a neuron to disgorge itself of a neurotransmitter that then binds with its receptors in the receiving neuron, stimulating a nerve impulse. Because these processes control everything in our bodies from the beating of our hearts to breathing, digestion, reproduction and mood, it’s hard to separate the reality of what we might describe as a subjective (spiritual) state from its neuro-chemical underpinnings.
Glutamate Suppressing Drugs
The cough-suppressant medication Dextromethorphan (DXM) illustrates this quite well. Commonly found in non-prescription treatments for dry cough, DXM is actually a dissociative general anaesthetic. The dose indicated for treating coughs is low enough that most people are free of negative side effects, but higher doses may result in unwanted psychedelic experiences. The related anaesthetic Ketamine was withdrawn from use in adults for this very reason, and is now used only in children and animals. Both of these therapeutics act by blocking one of the Glutamate receptors – the N-Methyl-D-Aspartate (NMDA) receptor.
Glutamate is the most commonly occurring neuro-transmitter in the human brain and one of the NMDA receptor’s primary functions is to maintain the connection between our conscious minds and the realities of our bodies and their surrounding environments. Progressively blocking these receptors with DXM or Ketamine leads to increasing levels of dissociated feeling. Complete blockade of the NMDA channel is not fatal, but does allow consciousness to persist while transporting the mind to surreal realms where the perception of space and time is completely transformed. While in this state one subject described living an entire lifetime as paint on a wall! A little reading about DXM reveals its plant-based provenance in that it is the Dextro stereoisomer of the synthetic opioid Levomethorphan. It has the same chemical formula as Levomethorphan but is its mirror image. This structural difference vastly changes the way it interacts with neurons - although technically an opioid it doesn't bind with opioid receptors at all.
The scale and complexity of receptors is mind-boggling. Take for example this crystallographic model of the NMDA receptor:
The N-Methyl-D-Aspartate Glutamate Receptor
This receptor is a protein that is synthesized from a single member in the human genome. It’s a pretty smart little machine. It contains a central Calcium ion channel that is opened or closed depending on how the filaments of the protein are stretched out or compressed. The stretching or compression of the filaments, known as a conformational change, depend on how the atoms in other molecules line up, and how their electrical charges attract or repel the corresponding atoms in the receptor. The NMDA receptor is agonized (activated or opened) by Glutamate and held shut by DXM and Ketamine (as well as laughing gas, PCP and other compounds). Unlike most receptors the NMDA receptor will not open when bound by Glutamate alone – it also requires the presence of the amino acid Glycine. Despite its undeniable complexity it is so tiny that you’d have to line up 10,000 of them in a row to equal the thickness of a human hair.
The Neuralsim Synapse Simulator
In order to get some inexpensive practical experience working with the processes and mechanisms underlying addiction I decided to write a simulator called Neuralsim. I just released an updated version today which you’re welcome to play with. It runs in a web browser on pretty much any platform, although it’s optimized for smart phones and tablets. You'll need to reduce the width of your desktop browser to emulate the width of a phone for best results. The concepts underlying this simulator are as follows:
- A single generic neuron type is presented into which you can insert plug-and-play components.
- The neuron is preceded by a synapse on the other side of which is the axon terminal of the preceding neuron.
- You are responsible for adding synaptic vesicles containing neurotransmitters to the upstream neuron. You must also add receptors to the downstream neuron. You can do this via the Receptors page.
- The neuron won’t fire if it doesn’t have a good supply of ions to work with. You can set ion levels using the Electrolytes page.
- Ion channels are always required, in addition to receptors, to ensure the signal is propagated properly. VGCA Ion Channels must be added to the upstream neuron in order for the synaptic vesicles to release their neurotransmitters. CNG Ion Channels must be added to the downstream neuron if you want your metabotropic receptors to work. You can add both of these using the Channels page.
- You can also add various therapeutic agents to the fluids surrounding the neuron. These include stimulants, pain killers, anti-psychotics and sedatives. These can be added using the Therapeutics page.
- You likely won’t want to do any of these things, so I’ve created a list of presets from which you can import your neuron parameters. Select the “Click here for help” link at the top of the main page to find out how.
While this simulator emulates the low-level functioning of a single neuron, it can’t explain concepts such as mood, emotion, motivation and desire. To explore these ideas we’ll have to look at how millions of neurons are combined to form the many different organelles making up the human brain (something tackled in the book). It does, however, illustrate how combining various therapeutics can have negative effects. Bad outcomes from drug combinations usually stem from under-stimulation or over-stimulation, so if your neuron won’t fire you may have discovered a lethal drug combination.
Disclaimer: As this app is in the early stages of development I can’t guarantee that all combinations of components will work together, or that all of the functionality has been implemented yet, however, the presets are working (mostly).
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