Adderall® is a powerful simulant psychoactive drug that causes structural, chemical, and functional changes in the brain. Among other amphetamines, it is one of the most misused and abused prescription medicines in the United States. When abused, the toxic effects of Adderall on the central nervous system (CNS) can lead to lasting physical, behavioral, and psychological disturbances.
Neurochemical and Structural Brain Effects
Adderall is a mixture of amphetamine and dextroamphetamine salts primarily used to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy. Even therapeutic doses can cause undesirable CNS side effects of changes in mood and behavior, reflecting its neurotoxic potential when the drug is abused.
According a 2009 review in Molecular Psychiatry, taking higher or more frequent doses of Adderall can lead to lasting toxic effects including:
- Decreases in the amount of the neurotransmitters present at the interfaces (synapses) between nerve cells in the brain
- Damage to the structure and function of nerve pathways and terminals in vulnerable areas of the brain
These changes can have significant health consequences.
Neurotransmitters and Adderall
The Molecular Psychiatry article notes through various mechanisms, prescription doses of amphetamines like Adderall relieve the symptoms of ADHD by increasing the related monoamine neurotransmitters, dopamine, norepinephrine, and serotonin in the synapses between nerve cells.
The increase in dopamine is the main neurotransmitter that leads to relief of ADHD symptoms. The resulting euphoria, alertness, and energy boost underlies the abusive potential of Adderall and other amphetamines. Based on several studies, Adderall abuse appears to be most damaging to the brain's dopamine nerve pathways.
Sources of Evidence of Brain Damage
Evidence for brain damage from Adderall comes from observations of the behavioral and psychological effects on misusers or abusers of amphetamines and methamphetamines, a derivative of amphetamine.
Additional evidence for adverse neurotoxic effects come from animal studies on these drugs. The neurotoxic brain damage caused by the drugs vary among animal species, which may reflect differences in susceptibility, so it is not yet clear if all the animal findings apply to humans.
Animal Studies
The following is a sample of studies exploring the damaging effects of amphetamines and methamphetamines in animals.
Baboon and Squirrel Study
This is an amphetamine study on baboons and squirrel monkeys published in 2005 in the Journal of Pharmacology and Experimental Therapeutics. Researchers administered doses of amphetamines similar to doses of Adderall used to treat ADHD in humans. On autopsy, they found that even with these therapeutic doses, in nerve fibers in the striatum of the brain, there were deficiencies in:
- Dopamine and the dopamine production enzyme, tyrosine hydroxylase
- The dopamine transporter system (DAT) and the vesicular monoamine transporter (VMAT2), which are both involved in movement of dopamine across nerve cell membranes to and from the synapses
These findings reflect evidence of amphetamine toxicity.
Rats and Other Animal Studies
The Molecular Psychiatry review reports that in rat and other animal studies, high doses and binge dosing of amphetamines interfere with serotonin and primarily dopamine nerve terminals. Amphetamines caused the following disturbances in the striatum of the basal ganglia (the area of the brain with the most dopamine input), and the prefrontal cortex of the brain - all evidence of damaged dopamine-containing nerve terminals:
- Structural damage to nerve cell body projections (dendrites) and axons of dopamine-containing cells
- Decreased dopamine in the synapses between nerve cells
- Decreased enzymes for dopamine production, such as tyrosine hydroxylase
- Deficits in the dopamine transporter system
- Damage to the vesicular monoamine transporter system
A Monkey Study and Human Psychosis
According to the researchers of a monkey study reported in 2007 in Neuropsychopharmacology, the damage to dendrites in the prefrontal cortex resemble the changes seen in humans with schizophrenia. They surmise this could explain the enduring cognitive deficits and schizophrenic-like stimulant psychosis seen in some people sensitized to amphetamines.
Human Studies
Evidence for the structural, chemical, and functional brain changes possible with Adderall and other amphetamines and methamphetamines comes from imaging studies, such as MRI and PET scans, as well as autopsy studies.
In a 2007 Addiction journal supplement, National Institutes on Drug Addiction researchers published a review of imaging studies of people who abused methamphetamines - similar to the neurotoxicity of amphetamine abuse. These human imaging studies show disturbances in the striatum of the basal ganglia similar to those seen in animal models of amphetamine abuse.
Potential Mechanism for the Damage to Nerve Terminals
The potential mechanism for the damage to nerve terminals by Adderall comes from analyses of the animal research on the neurotoxicity of methamphetamines. The authors of one such analysis, published in 2003 in the Journal of Pharmacological Sciences, concluded the disruptions caused by methamphetamines (therefore amphetamines) lead to accumulation of dopamine in the cytoplasm of nerve cell bodies.
This dopamine accumulation in nerve cells causes production of reactive oxygen species (free radicals) leading to oxidative stress and the damage to dendritic and axonic nerve terminals, although the cell bodies remain undamaged. These brain damages appear to persist for years even after stopping the drug, according to the 2007 Neuropsychopharmacology study.
Long-Term Behavioral and Psychological Effects
Therapeutic doses of Adderall are effective and safe and have minimal risk of long-term adverse effects. However, people who abuse Adderall may have long-lasting behavioral and psychological dysfunctions because of the structural and neurochemical brain damages. These CNS effects include:
- Hyperactivity and anxiety
- Depression, moodiness, and insomnia
- Learning and memory impairment
- Movement disorders
- Psychosis, paranoia, and hallucinations, especially in those with preexisting psychosis
- Physical and psychological dependence on the drug and risk for addiction
Although the drug decreases hyperactivity in people with ADHD, Adderall often overstimulates the brain of those without it. This is even more so for those who misuse the drug by taking higher or more frequent doses. The effect of Adderall on other organs cause the other long-term effects seen in people who abuse the drug.
Factors That Affect Neurotoxicity of Adderall
Several factors may affect the impact of Adderall on the brain and the risk for brain damage, including:
- Age: Animal studies suggest amphetamines like Adderall are less toxic to adolescent and young adult brains than older adults, as reviewed in a 2015 article in the International Journal of Developmental Neuroscience.
- Gender: Women may be more susceptible to sensitization to Adderall and its neurotoxic effects because of estrogen and progesterone, as explored in an article in Pharmacology, Biochemistry and Behavior.
- Prior exposure: Prior exposure to non-toxic doses of amphetamines may protect against the neurotoxic effects of higher doses, as demonstrated in rat studies, according to a report in the journal Synapse in 2006.
- Stress: According to animal studies, such as a rat study reported in Neuroscience in 2004, stress can increase the neurotoxic effects seen with amphetamine abuse.
- Drug dose: The larger the dose of Adderall and the more frequently it is abused, the greater the risk for brain damage. This is also true if Adderall is snorted or taken by routes other than by mouth.
Mixing Adderall with other drugs, such as alcohol, can also increase the risk of of brain damage and death, especially in a situation of alcohol poisoning.
Use Adderall Only as Prescribed
Adderall, like other amphetamines, is frequently misused and abused for nonmedicinal purposes. Even in therapeutic doses, it can have toxic effects in the brain that may be short-term and reversible. With abuse of the drug, this neurotoxicity can be more severe and permanent and lead to severe health consequences. Take Adderall only if you need it for medical reasons and use it only as prescribed by a doctor.
