STIMULANT MEDICATIONS AND THE DOPAMINE CONNECTION

Our brains are made up of nerve cells called neurons, which are separated by tiny gaps called synapses. All brain and nervous system functions are based on how these neurons communicate across synapses. The neurons relay information to each other by sending chemical messengers, i.e., neurotransmitters, across the synapses throughout the neural network. The neurotransmitter may then be accepted by the next neuron attaching at a site called a receptor, thereby transmitting information from one nerve cell to another throughout the brain. In order for these pathways to work effectively, the neuron must produce and to release enough of the neurotransmitter. Furthermore, the neurotransmitter must stay in the synapse long enough for it to bind to the receptor site. After the neurotransmitter is released, the excess portion is then reabsorbed by the neuron that produced it. Within the ADHD brain, the neurotransmitter, dopamine, is prematurely reabsorbed back into the neuron. When this occurs, that portion of the neural network cannot relay messages in an adequate and timely way. Dopamine is the brain’s supreme neurotransmitter, in terms of memory, focus, motivation, pleasure, motor skills efficiency, and communication skills, thus its deficiency can have severe consequences upon an ADHD individual’s overall quality of life.

Psychostimulants, including Adderall (amphetamine and dextroamphetamine) and Ritalin (methylphenidate), have been the major pharmacotherapies for individuals with ADHD. The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity, which impacts executive and attentional functioning. Amphetamine actions include dopamine and norepinephrine transporter inhibition, vesicular monoamine transporter 2 (VMAT-2) inhibition, and monoamine oxidase (MAO) activity inhibition. Methylphenidate actions include dopamine and norepinephrine transporter inhibition, agonist activity at the serotonin type 1A receptor, and redistribution of the VMAT-2.

Stimulant medications reduce ADHD symptoms by increasing the dopamine levels in your brain. It does this by slowing down how much dopamine is reabsorbed back into the neural network. As a result, more neurotransmitter is held in the synapse between neurons long enough for it to properly bind to the receptor, helping messages within the brain be more effectively transmitted and received. This improves activity and communication in those parts of the brain which operate on dopamine and norepinephrine and signal for specific tasks.

The immediate psychological effects of stimulant administration include a heightened sense of well-being, euphoria, alertness, and increased motor activity. Stimulants may also reduce appetite, may result in insomnia, and may enhance libido. Amphetamine-based stimulants include Adderall (amphetamine dextroamphetamine), Dyanavel XR (amphetamine), and Vyvanse (lisdexamfetamine dimesylate). Common methylphenidate-based stimulants include Concerta (methylphenidate extended-release tablets), Focalin (dexmethylphenidate), Metadate (methylphenidate hydrochloride), and Ritalin (methylphenidate).

Research shows that stimulant medications increase levels of dopamine by acting as dopamine reuptake inhibitors, referring to their role in limiting the reabsorption of dopamine by the postsynaptic neurons at the dopamine receptor sites. The result is a “flooding” of dopamine in the extracellular synaptic clefts between neurons along the brain’s pleasure, focus, and motivation pathways. The greater levels of dopamine in the synapses create a heightened state of wakefulness, more focused attention, and enhanced cognitive abilities. This could explain why some people who misuse prescription stimulants, such as young adults in college, often do so to improve their concentration and alertness, which they perceive as helping with their studying and academic performance.

Stimulant medications also serve as dopamine agonists, which means that they activate dopamine brain receptor sites and cause increased dopamine production in key areas of memory, attention, and information-processing. This increase in dopamine contributes to a reduction in ADHD symptoms, particularly the pattern of hyperactivity, poor concentration, impulsivity, and thought confusion. The reduction of these symptoms results in a greater sense of calmness, focus, and well-being. By increasing levels of dopamine in the brain, prescription stimulants, when taken appropriately, can produce very positive effects upon ADHD individuals’ academic, professional, and personal functioning, and these effects tend to remain stable over time.

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