WHY DO AMPHETAMINES HELP PEOPLE WITH ADHD?

There has been a lot of concern expressed about amphetamines being prescribed for ADHD in children and adults. There is concern about addictions and dependence on these medications. It had been thought that these medications work by influencing neurotransmitters [serotonin, norepinephrine and dopamine]. These neurotransmitters are influenced by amphetamines. However, my patients have never responded to these medications as if they were amphetamines when they are helping them to focus. In fact, if my patients do respond to these medications as amphetamines [typically with increased energy, restlessness and irritability, appetite supression and difficulty falling asleep], they interfere with focusing and concentration and if they persist indicates a need to try another medication in the other group of medications for ADHD. When my patients respond to these amphetamine medications with improved focusing and concentraton, they are calmer, more alert, more able to complete tasks, less likely to finish tasks at the last minute and are less socially anxious. My patients who have problems with concentration [are ADHD], do not respond to these medications like they are amphetamines.

So why might that be the case. There is recent research suggesting that in people with ADHD, amphetamines influence the white matter [WM] portion of the brain that is deeper in the brain then the gray matter [GM] where our emotions, moods, anxiety, fears, etc., are. The WM is where the so called long tracks are located that function to connect different parts of the GM together and thus serve to help to coordinate brain activity and maintain stability, even when the emotions are activated. This location for concentration could serve to protect our ability to concentrate from the ups and downs of our emotional lives and preserve our ability to concentrate even if we are upset. This has not been demonstrated to occur in brains as it is difficult to see the WM with MRI's except by measuring the diffusional motion of water molecules using Diffusion Tensor Imaging [DTI] that assesses the micro-structural features of white matter studies that have found delays in brain white matter development in people with ADHD. This work has been added to by Bouziane, et.al. ADHD and maturation of brain white matter: A DTI study in medication naive children and adults" in Neuroimage Clin. 2018; 17: 53-59. who studied medication naive children and adults using DTI. They found that the WM of children with ADHD were the same as children without ADHD while adults with ADHD had reduced fractional anisotropy [FA] compared to adults without ADHD in several regions and the anterior thalamic radiation. FA is a normalized measure that quantifies the directional anisotropy of diffusion and is thought to reflect fiber density, axonal diameter and myelination in white matter. It is now thought that WM changes in people with ADHD occur in adults and not children. However, animal studies [van der Marel et al.Long-term treatment of adolescent and adult rats: differential effects on brain morphology and function. Neuropsychopharmacology; 2014;39:263-273] have shown that methylphenidate [a medication used to treat people with ADHD] in animals has upregulated the striatal genes that are involved in axonal myelination and thesse changes might be the changes seen in WM in people who are treated for their ADHD and thus supporting that these medications work in the WM part of the brian. 

So it seems that people with ADHD respond to amphetamine type medications with improved focus and concentration and not with responses that are typically associated with amphetamines. This would explain the benefit of these medications for people with ADHD and why they tolerate them without the problems that can be connected to taking amphetamines. In fact, research has repeatedly demonstrated that treating ADHD in young adolescents will reduce their risk of having an addiction. None of the thousands of people that I have treated with amphetamine type medicatons for ADHD have abused these medications.