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Amphetamine Use in The Treatment of ADHD

Updated on December 19, 2013

A Brief History of Amphetamines

Ephedrine is a synthetic stimulant closely resembling adrenaline in organic structure and physiological effect upon the nervous system. This chemical was derived from the Ma-Huang plant (Ephedra) by Nagayoshi Nagai in 1887. In the same year Lazar Edeleanu, a chemist working in Berlin, used Ephedrine to synthesize a chemical he called Phenylisopropylamine. It would become commonly known as Amphetamine.

Limitation of access to Amphetamine compounds such as Adderall first came in 1965 when the FDA first required a physician’s prescription to obtain them. In the Controlled Substance Act of 1971 Amphetamines became a schedule two controlled substance alongside most types of prescription opiates and other stimulants such as cocaine and methamphetamines.

Medicinal, Recreational, and Other Uses of Amphetamines

The two conditions for which Amphetamine salt based compounds are most commonly prescribed are ADHD (all four subtypes of Attention Deficit/Hyperactivity Disorder) and Narcolepsy. It is occasionally used, “off-label” to treat extreme obesity because, like most stimulants, it suppresses the appetite and also very rarely is used to treat extreme and prolonged depressive symptoms.

It is manufactured in denominations typically between 5 and 30 milligrams and a therapeutic dosage is considered between 5 and 60 milligrams depending on the patient and the type and severity of their symptoms.

Like any stimulant Amphetamines can and is used recreationally for the euphoric feelings that accompany its use in higher quantities.

More interesting is the historic and current widespread and multifaceted use of drugs of this kind as performance-enhancers. It has (and is) used by militaries around the world including the U.S. during WW II to foster energy, concentration, and alertness in soldiers. Athletes, professional and amateur, especially Major League Baseball players (until Amphetamines were banned in 2006) have used these types of stimulants for their energizing effects and there is an epidemic of ambitious high school and college students that take Amphetamines in various forms to increase concentration and foster other areas of cognitive performance.

"Ball and Stick" Model of Amphetamines' Organic structure

Biochemistry of Amphetamines

Amphetamines are known to work on three neurotransmitters; Dopamine, Serotonin, and Norepinephrine. Two theories concerning its effect in the synaptic clefts between neurons are postulated to explain Adderall’s ability to deliver more Dopamine to the Frontal Cortex where the increased presence of this Dopamine improves concentration and alertness. These theories also imply a higher concentration of Dopamine to the Limbic System where it enhances working memory and the executive functioning involved in intentional focus.

The first of these non-mutually exclusive theories are that Amphetamines augment the amount of Dopamine levels in the Presynaptic Cytosol (intercellular fluid) so that it is released in greater quantities into the gap causing a greater incidence of Dopamine uptake by the Postsynaptic Dopamine receptors.

The second theory is that it actively fosters the activity of the protein responsible for Dopamine transport, DAT (Dopamine Active Transport), improving the efficacy of Dopamine transport from the cleft back to the Presynaptic Cytosol where the Dopamine has the opportunity to be re-released into the Synaptic gap and another chance to be taken-up by the Postsynaptic Dopamine receptors.

For the neurotransmitter Serotonin, Amphetamines are thought to act much like an SSRI (Selective Serotonin Reuptake Inhibitor) in that it inhibits the response of the protein SERT (Serotonin Transporter) which acts to reuptake Serotonin from the synaptic cleft back into the Presynaptic neural Cytosol before it has had a chance to be received by the Postsynaptic Serotonin receptor sites. This inhibitory response of the SERT protein allows elevated amounts of Serotonin to be distributed to every lobe of the Cerebral Cortex and to parts of the Limbic System.

Norepinephrine has its own protein that acts as an active transporter of Norepinephrine out of the Synaptic cleft. Adderall is thought to concentrate norepinephrine in the blood and in the brain, specifically in the Nucleus Accumbens, the Stratium, and the Prefrontal Cortex in the same way that it elevates Serotonin levels in the Cerebral Cortex and areas of the Limbic System.

While it does seem paradoxical that a stimulant would be efficacious in treating ADHD patients, these patients are thought to have an insufficient amount of Dopamine in the Prefrontal Cortex resulting in hyperactivity, distractibility, and impulsivity. The augmented levels of Dopamine supplied by the chemical intervention of Adderall and other amphetamine based drugs seem to help with attention, focus, and decision making.

Efficacy, Side Effects, and Limitations of Amphetamines

As a quick fix for the symptomology associated with ADHD, Amphetamine salt based compounds have become the gold-standard. The consensus seems to be that it is an effective intervention for 80-90% of people prescribed it or some medication like it.

Amphetamines are counter-indicated for people with heart problems, high blood pressure, Bipolar Disorder, Schizophrenia, a history of seizures or epilepsy, Tourette’s syndrome, hyperthyroidism, glaucoma, or if the patient is pregnant, thinking of becoming pregnant, or is breast-feeding.

Side effects range from mild to more problematic, even when taken as prescribed, and include increased blood pressure, anxiety, euphoria or dysphoria, shortness of breath, seizures, tremors, ticks, or confusion, and burning during urination. Less severe side-effects include dry mouth, insomnia, irritability, loss of appetite, nausea, diarrhea, and sexual complications.

Further, all Amphetamine based compounds have the potential to become habit-forming and for abuse. In heavy stimulant users there is a risk for stimulant psychosis which mimics an organic psychosis and includes hallucinations, delusions, and disordered thinking. Five to fifteen percent of patients studied by one set of Japanese researchers suffering from such a psychosis never made a full recovery.

Alternative and Concurrent Therapeutic Options for Managing ADHD

There are a number of non-controlled substances, without the potential for addiction or abuse, that have been shown to have some efficacy when used off-label to treat ADHD. Antihypertensives and Antiadrenergics along with a particular Aminoketone Antidepressant should be looked into as alternate Psychopharmacological courses of treatment.

Diets high in dietary fibers and low in processed sugars, artificial preservatives, and artificial colors or flavors are recommended for patients experiencing ADHD symptoms but changes in diet in and of itself have shown little impact on symptoms. Basic parental Psycho-education concerning the condition; including parenting skills, child safety, and techniques such as operant conditioning are also a concurrent treatment option regardless of what type of Psychopharmacological treatment is being employed.

There are two behavioral treatments of note based upon interesting hypothesis but, as of yet, not supported by much empirical evidence that may relieve some symptoms of ADHD. Interactive Metronome Training involves rhythmic kinesthetic movement to strengthen the motor training/timing deficit thought to be associated with ADHD.

Another behavioral approach, Neurofeedback Training uses an EEG to train the client to increase prefrontal lobe arousal by increasing beta brain waves while decreasing theta waves. Research has shown a consistent excess of theta waves and a dearth of beta wave activity in the Frontal Cortex of ADHD suffers in comparison to non-ADHD suffers.

Addressing The Controversy

The use of Amphetamine salts should involve a careful and informed decision made by the parents, physicians, teachers, and other mental health clinicians on a case by case basis. The choice should depend upon a consideration of the severity of the symptoms, the known side effects of the compound, and the mutual goals concerning symptom management.

Careful and thorough evaluations are needed to ensure an accurate diagnosis which is not being confused with Oppositional-Defiance disorder or with behavior stemming from developmental and situational sources. Once a diagnosis is made medications such as Clonidine, Wellbutrin, and Strattera might be administered along with behavior interventions and the patient monitored for symptom amelioration before Amphetamines are considered.

In cases where these measures, involving non-addictive medications are found to be insufficient, the carefully monitored use of low doses of Amphetamine based drugs might be the difference between reaching normal academic and social milestones or an emerging pattern of anti-social behavior and developmental delays.


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    • mperrottet profile image

      Margaret Perrottet 

      5 years ago from San Antonio, FL

      I'm concerned about the long term effects of adderall and other similar drugs on our children. I think that ADHD is being over-diagnosed, and that too many of our children are on drugs. This is a very thorough well-written article on adderall's history and usage. Voted up, interesting and useful.


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