The children in the study were followed into adolescence and adulthood. It turned out that the children who were better at inhibiting the impulse to immediately eat the one marshmallow were more resilient, confident, and dependable as adolescents. They also scored higher on standardized tests such as the SAT. While a controversial study with some methodological problems, the results were interesting, nonetheless.

Dopamine and norepinephrine are two very important brain chemicals involved in attention, movement, and impulse control. These two chemicals work together to filter out irrelevant stimuli while enhancing the relevant stimuli. In individuals with ADHD, these two chemicals appear to be imbalanced or “out of tune.” By enhancing these brain chemicals with medications, therapy, and neurofeedback, we can improve symptoms dramatically!

ADHD and Criminality 

• Studies have estimated the prevalence of ADHD among male prison inmates to be around 40% (Rösler et al. 2004; Ginsberg et al. 2010).
• In the absence of comorbid conduct disorder, ADHD patients had no higher risk for delinquency than adults with other childhood psychiatric disorders (Gjervan et al. 2012).

• Hyperactivity: Inner restlessness, Talkativeness, Excessive fidgeting, high risk activities

• Impulsivity: Impatience – “talking without thinking”, difficulty maintaining employment, difficulty maintaining relationships, attention seeking behavior, high risk behaviors, self-medicating

• Inattentiveness: Feeling bored, indecisive, procrastination, disorganization, easily distracted

• Common complaints in adults with ADHD include rapid mood swings, difficulties dealing with stressful situations, frequent irritability and frustration, emotional excitability (anger over minor things), relationship problems (short-lived, divorce), and coping with one or more children with ADHD.

**ADHD IS NOT RELATED TO INTELLECT**

Differentiating ADHD from Bipolar Disorder can be difficult because many symptoms overlap and both disorders often co-occur (that is, many patients have both ADHD and Bipolar Disorder). Below is a table differentiating the two.

The term stimulant or psychostimulant isn’t well defined. Cocaine, amphetamine, methylphenidate, modafinil, armodafinil, caffeine, and nicotine belong to this class of drugs, which are called stimulants for the marked sensorimotor activation that occurs in response to drug administration. Stimulants are characterized by their ability to increase alertness, heighten arousal, and cause behavioral excitement. Psychostimulants are prescribed for the treatment of attention-deficit hyperactivity disorder (ADHD), narcolepsy, chronic fatigue, depression, and cancer-related fatigue to name a few. Stimulants are also drugs of abuse (such as cocaine, illicit methamphetamine, nicotine, and caffeine).

Let’s take a closer look at psychostimulants and how they work. 

Dopamine and Norepinephrine

Neurons are cells in our brain that communicate with each other like telephone wires. Each neuron can communicate with or “talk to” thousands of other neurons using chemicals called neurotransmitters. The most abundant neurotransmitters in the brain are glutamate, which generally excites other neurons, and GABA, which generally inhibits other neurons. Dopamine (DA), serotonin (5-HT), norepinephrine (NE), acetylcholine (ACh), histamine, cannabinoids, and other neurotransmitters play very important roles in altering the communication between neurons.

Interestingly, dopamine (DA) and norepinephrine (NE) are neurotransmitters with important roles in attention, arousal, energy, motivation, pleasure, reinforcement, movement, learning, memory, and mood states.

DA and NE are stored in neurons within small bubbles called vesicles. These vesicles are released into an area between two neurons called the synaptic cleft. DA and NE then bind to receptors located on other neurons (including the same neuron that released them) to communicate a signal. DA and NE are then recycled or “vacuumed” back into the neuron by specific transporters called dopamine transporters (DATs) and norepinephrine transporters (NETs), respectively.

The recycled dopamine and norepinephrine are pumped back into vesicles via the vesicular monoamine transporter 2 (VMAT2) and are stored for the next cycle. Stimulants like amphetamines, methylphenidates, and cocaine increase dopamine and norepinephrine in the synapse by various mechanisms which are discussed in more detail below. 

Amphetamine, AMPH (Vyvanse, Dexedrine, Adderall)

Amphetamine (AMPH) has numerous mechanisms. First, it can be taken up into neurons via the dopamine transporter or norepinephrine transporter which then reverses its actions to promote the release of dopamine.

AMPH also enters vesicles through VMAT2 and displaces dopamine by “forcing” dopamine out of the vesicle and into the cytoplasm. Increased cytoplasmic dopamine concentrations cause passage of dopamine through the DAT into the synapse thereby increasing the dopamine concentration in the synaptic cleft.

Mechanism of Action of Amphetamines

Methylphenidate, MPH (Ritalin, Concerta, Focalin)

Methylphenidate (MPH) acts by inhibiting the dopamine and norepinephrine transporters which increases the concentrations of dopamine and norepinephrine in the synapse.

Mechanism of Action of Methylphenidates

In individuals with attention and/or concentration problems, there may be a problem with how the brain is processing sensory input. Our brains spend an enormous amount of energy (up to 20-30% of all energy used by your body) processing information below our level of awareness. In fact, only a very small percentage of brain activity contributes to our conscious awareness (roughly 15%). The rest of the activity is all the unconscious processing, integrating, and analyzing of information that ultimately results in complex behavior. 

Much of the brain’s energy is spent “deciding” which signals are relevant and need to be brought to conscious awareness. Think of all the activities we do that we aren’t even aware of. 

While walking down the street talking with someone, do you actively feel your left big toe? Well, no, not unless you have pain or stub your toe. We aren’t aware of our left big toe because it’s irrelevant to what we are doing. But this doesn’t mean those signals are physiologically absent. 

Dopamine and norepinephrine are neurotransmitters in the brain that act like the tuners of a piano. The strings of the piano that create the sounds represent the glutamate and GABA neurons that are the primary excitatory and inhibitory neurotransmitters in the mammalian brain, respectively. Dopamine and norepinephrine are there to tighten the strings so the music sounds good.

No one likes a song that’s out of tune. That is, dopamine and norepinephrine are those “tuners” of the brain–they modulate communication between neurons. They help our brain decide what to ignore and what to focus on.

In fact, norepinephrine in the prefrontal cortex (PFC) plays a role in enhancing relevant and important signals so that we focus on relevant and important things.

Low-to-moderate concentrations of norepinephrine (NE) mediate these actions by acting preferentially on postsynaptic 𝛼2A-adrenoceptors. However, as the concentration of norepinephrine increases, norepinephrine begins stimulating 𝛼1 and 𝛽-adrenoceptors. Stimulation of 𝛼1-adrenoceptors and 𝛽-adrenoceptors (which occurs in high stress states) impairs our ability to focus.

When the NE concentration is too low, the signal strength (i.e., our ability to focus on things) is low. As the NE concentration increases so does the signal strength (i.e., our ability to focus on things) until it reaches a peak. Any additional increase in NE impairs, rather than enhances, our ability to focus. This explains the inverted U shaped curves depicted below.

Dopamine in the prefrontal cortex (PFC) plays a role in filtering out the irrelevant stimuli. That is, dopamine D1 receptors in the prefrontal cortex reduce the “noise” or irrelevant stimuli so that we can focus on relevant and important things without being distracted.

When DA levels are too low, all incoming signals, whether they are relevant or not, are treated in the same way. Therefore, it becomes difficult to focus on a single task as there are too many distracting stimuli. However, as the concentration of DA increases to moderate levels, it will decrease ‘noise’ by stimulating D1 receptors. This results in decreased firing of neurons to irrelevant inputs in PFC networks.

When DA levels are too high, D1 receptors in the prefrontal cortex are overstimulated and the brain’s ability to filter out the noise declines. Stressful situations and illicit drug use can cause dopamine levels to be too high.

Therefore, medications like amphetamines (Vyvanse, Adderall), methylphenidates (Ritalin, Concerta, Focalin), bupropion (Wellbutrin), and atomoxetine (Strattera) alter norepinephrine and/or dopamine levels to “enhance the signal” while “reducing the noise,” respectively.

Medications (or illicit drugs) that enhance dopamine too much in certain regions of the brain may cause us to “hyper focus” or “fixate” our attention on unproductive tasks. In addition, the euphoria and motivational reinforcement that results from overstimulation of dopamine receptors in the nucleus accumbens increases the risk for addiction and drug abuse.

In summary, we don’t want too much stimulation of dopamine (D1) receptors because this is associated with euphoria, hyper focus (like scrubbing the floor with a toothbrush), impaired attention, and drug addiction. We don’t want too little stimulation of dopamine (D1) receptors because this is associated with anhedonia, depression, lack of motivation, and apathy.

The same goes for norepinephrine. We don’t want too much norepinephrine because then we will feel symptoms associated with the fight or flight response such as anxiety, hypervigilance, racing heart, sweating, and shortness of breath. We don’t want too little norepinephrine because then we will feel symptoms like fatigue, depression, drowsiness, and weakness.

Therefore, we want our DA and NE to be not too hot and not too cold, but just right (yes, like Goldilocks). This is why controlled doses of stimulants can be very beneficial for some people.