The Dope on Dopamine

For the past several decades scientists have been investigating possible connections between ADHD and one of the main chemical messengers in the brain, dopamine. Scientists noticed that medications that work for ADHD all lead to increases in dopamine at connections between brain cells. The simplest explanation seemed to be that the medications work by helping to fix a broken dopamine system in the brains of ADHDers.

When it comes to biology, however, the simplest explanation is not always correct - and the issue is not so easy to settle. One of us (Ben) is a brain scientist – so let’s talk a little about what is really known and not known about dopamine and ADHD.

Dopamine is a neurotransmitter – a chemical that transmits signals between specialized brain cells (neurons) at their connections (synapses). It is one of several major neurotransmitters in the brain (not only in humans, in the brains of all animals). Its chemical structure is very closely related to another neurotransmitter called norepinephrine (which is closely related to the hormone adrenaline, also called epinephrine) - but the effects of dopamine are quite different.

Most or all of the drugs currently used to treat ADHD do indeed increase the effectiveness of dopamine at synapses. Something about this helps patients with ADHD focus and pay better attention to one thing at a time. How exactly more dopamine translates into better concentration and focus is not yet understood. Separately, there is also some genetic evidence supporting a role for dopamine in ADHD. ADHD has a substantial heritable component, and at least a couple of the genes involved encode dopamine receptors – these are the molecules at your synapses that pick up dopamine signals.

But it’s certainly not simply a matter of “too little dopamine (or dopamine signaling) in the brains of ADHDers”. Dopamine’s role in the brain is far more varied and complicated for this to be the case. For example, not only is dopamine involved in focus and concentration, it is also a major player in the reward circuitry of the brain and for this reason is important in all forms of addiction (tobacco, alcohol, opiate & all other drug addiction, gambling, internet addiction, etc). It plays a role in a circuit involved in the production of the female nursing hormone, prolactin. It is also critical in the brain circuitry controlling smooth muscle movements that gets damaged in Parkinson’s Disease; muscle rigidity and abnormal jerking movements are one consequence of too little dopamine in that disease.

Not only ADHD medications, but other psychiatric drugs also affect dopamine. Antipsychotic medications alter dopamine signaling in roughly the opposite direction of the ADHD medications. Antipsychotics, used to treat hallucinations and disorganized thinking in mental disorders such as schizophrenia, decrease the effectiveness of dopamine at synapses everywhere in the brain. The blockade of dopamine in some of the circuits we just mentioned can cause unwanted side effects from these medications, such as muscle rigidity or milk production (even in men) – while the blockade of the signal in other brain areas such as the cerebral cortex (the outermost layers of your brain) appears to be helpful in reducing hallucinations and disordered thinking.

To make matters even more complex, each individual has their own particular genetic variation in receptors for dopamine and other neurotransmitters. Not only is the amount of dopamine important, but the many different types of receptor present in distinct regions of your brain, and the extremely complex ways these regions are all wired together, contributes to how you react to levels of dopamine and other neurotransmitters in your brain, and to medications that alter this balance.

It would be super-cool if your doctor could scan your brain or your DNA and see your levels of dopamine, all your other neurotransmitters, the mix of signaling molecules inside your (100 billion) brain cells, the types of receptors present at your (100 trillion) synapses, the complex circuitry that wires all this together – and based on that predict how you will respond to a medication. But at this point that is pure science fiction!! There is no scan available today that can reveal in sufficient resolution your neurotransmitter levels, receptor subtypes, and the myriad other factors underlying the functional anatomy of ADHD (or addiction, or Parkinson’s Disease, or schizophrenia...). And even if we had the technology to perform such a scan we would have no idea how to interpret the results! As the saying goes, that day may come—but today is not yet that day.

So take the popular “hype” about dopamine and other neurotransmitters with a huge grain of salt; a little knowledge can be a dangerous thing. The human brain is aptly described as the most complex structure in the known universe. Given that huge complexity, it is safe to say that brain scientists currently understand much much much less than 1% of it. We’re still just groping around the edges of beginning to understand how the brain is put together, let alone how it generates your thoughts and behavior. A lot of what doctors think they know about disorders such as ADHD has been inferred, rightly or wrongly, from how existing psychiatric drugs appear to work: i.e. “Drug A works in Disorder B and increases Chemical C. Therefore, Disorder B must involve too little Chemical C (in the brain).” That’s about as good as it gets – and frankly that’s not very good – so beware of anyone telling (and selling) you dietary supplements to increase brain neurotransmitter levels, kits to reveal other supposedly relevant aspects of your brain chemistry, or (for that matter) DNA scans to tell you what will work or not work in you or your loved ones. We’re still in an age of educated trial-and-error when it comes to almost all psychopharmacology – although with continuing research this will change - slowly at first, more quickly over time.

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