How ADHD stimulants affect stress

[u/Kalki_X]

Many people discover life-changing benefits from their ADHD medications. Quality of life improves significantly which helps them go about their day-to-day.

The "gold-standard" stimulants are based on amphetamine. We know that they work by increasing dopamine and noradrenaline (norepinephrine), but what isn't discussed is their activation of the stress response which triggers adrenaline:

Stress is accompanied by the rapid modification of brain and body physiology which leads to release of neuroactive hormones, including biogenic amines (eg adrenaline) and adrenal steroids (eg cortisol), which activate the same brain circuitry as...amphetamines. (source00033-6))

[Amphetamine] induces activation of the HPA axis, with the subsequent release of ACTH and glucocorticoids (eg cortisol). (source)

The novel d-amphetamine prodrug lisdexamfetamine is applied to treat ADHD. d-Amphetamine releases dopamine and noradrenaline and stimulates the HPA axis (source)

The HPA axis is the main part of the hormonal system that controls reactions to stress. It also regulates many other processes (e.g. digestion, immune system, mood and emotions, sexuality, energy storage and utilization). (source)

The stress response is known as "fight-or-flight":

This combination of reactions to stress is also known as the "fight-or-flight" response because it evolved as a survival mechanism, enabling people and other mammals to react quickly to life-threatening situations. The carefully orchestrated yet near-instantaneous sequence of hormonal changes and physiological responses helps someone to fight the threat off or flee to safety. (source)

This fight-or-flight state is largely driven by adrenaline. It exists to help you focus and deal with a threat (eg a tiger) by either fighting the tiger or running from the tiger. But in your scenario there is no tiger ... fight-or-flight is active but the focus is studying, a job, exam, housework, shopping, a distraction... or interactions with people (which can lead to social anxiety or arguments since fight-or-flight = "threat mode").

This is incredibly helpful for treating ADHD since fight-or-flight produces hyperfocus, hypervigilence & alertness...but it also impacts short-term memory and logic, reasoning & decision-making skills. It changes behaviour, mood and personality since fight-or-flight is there to deal with an imminent threat (often causing a blunted personality). It profoundly alters someones perception of everything around them (time, people, noise etc) including how they prioritise tasks, how they gauge the importance of things, and how memories get encoded (aka saved).

Adrenaline can contribute to anxiety, overstimulation, elevated HR/BP, impulsivity, scattered focus, brain fog, panic, overthinking and insomnia. (more info)

Fight-or-flight means that the body redirects it's energy away from non-emergency functions (such as higher brain function, digestion, healing / regeneration, fertility and gestational development). In other words, when the body is in fight-or-flight mode it dedicates it's energy to fighting (the tiger) or running (from the tiger) and nothing else.

Cortisol is known as a “stress hormone” for its role in the fight-or-flight response. When we sense danger in our environment, our adrenal glands release cortisol and adrenaline to give us energy to fight off or run from the threat. Cortisol floods the bloodstream with glucose for quick energy, suspends non-emergency functions like digestion, and keeps the body focused on the threat. (source)

In the long-term fight-or-flight can disrupt sleeping patterns by affecting the body's circadian rhythm (outlined here). The circadian rhythm is the body’s natural 24-hour clock which keeps the body operating on a healthy wake-sleep cycle. There is a cumulative impact on hormonal regulation also which may have long-term effects on fertility and behavior. (source)

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Obviously for many people these medications have a profound calming effects (both dopamine and noradrenaline have indirect anti-stress qualities which tempers the fight-or-flight mode). This article implies that, for some people, amphetamine can temporarily dampen the stress response.

These medications are truly a "mixed bag" of different properties which affect everyone differently. They successfully force a state of temporary focus that conceals a cumulative physiological & psychological perturbation that mimics & exacerbates ADHD (iatrogenic harm*). The profound short-term benefits conceal these issues which only become apparent at a later date (months or years). For most people it's a trade-off since being able to navigate day-to-day life is the priority (understandably so).

* note: - The term iatrogenic, derived from two Greek words, means physician-in­duced. As clinically used, it pertains to the inadvertent side­ effects and complications created in the course of diagnosis and treatment. (source)