Are Stimulants Neurotoxic?

Introduction:

The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) is well established in the field of psychiatry. Not only is it well accepted, but ADHD has dramatically increased over the past 10 years. Some would even say it’s an epidemic in its own right. The use of psychostimulants as a treatment is common practice, and today we are here to discuss the risk of neurotoxicity with ADHD medication.

What Are Psychostimulants

Psychostimulants include methylphenidate (MPH) and mixed amphetamine salts such as Adderall. These remain the most effective and widely used medications for the treatment of ADHD. These medications function by blocking the dopamine reuptake transporter and increase dopamine stimulation at the postsynaptic receptors. These medications work to increase attention and reduce impulsivity but the long-term implications of consistent use are largely unknown. 

Substance Use and Stimulant Prescribing

Most lines of evidence in the literature indicate that these medications do not promote substance use later in life and may even decrease the potential for future substance abuse. I’ve also found lines of evidence that indicate the opposite, but the general consensus in the field is that there is not increased risk for future substance abuse. We do know that drugs that function in a similar manner to these medications result in molecular and structural changes to neurons. It is unknown if this also occurs with stimulant medications used to treat ADHD. 

Neuronal Effects of Amphetamine

Methamphetamine is a known neurotoxin and several studies have indicated this in animal models. Recently exposure to amphetamine has been sown to cause impairments on the development of dendritic branching up to 3 months after stopping methylphenidate. In mice there is evidence that MPH use causes loss of dopamine neurons in the substantia nigra which may increase the risk of Parkinson’s disease. Other groups have shown alterations in nerve growth factors and brain derived neurotrophic factor in the frontal cortex after chronic MPH use. When neurons from the prefrontal cortex are exposed to MPH it alters their electrical activity. MPH was found to reduce electrical activity and it persists in a dose dependent fashion even 10 weeks post exposure. In rats the use of MPH is associated with decreased response to normal stimuli and increased response to adverse stimuli. We need to be careful extrapolating this information to humans as these studies were conducted in animal models. 

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