How ADHD medication works

In ADHD, the brain region prefrontal cortex (responsible for planning, focus, and impulse control) and their networks with the striatum and basal ganglia don’t regulate dopamine and norepinephrine efficiently.

• This leads to inconsistent attention, difficulty sustaining focus, impulsivity, and problems with motivation.
  
  
• Mechanism:
  • Increase dopamine and norepinephrine levels in synapses.
  • Block reuptake transporters (so neurotransmitters stay active longer).
  • Amphetamines also increase release of dopamine and norepinephrine from neurons.

• Effect:
  • Boosts signal strength in the prefrontal cortex, leads better sustained attention, working memory, and self-regulation.
  • Reduces “background noise” in the brain so relevant information is easier to focus on.

How ADHD medication works: click here for more details

Mechanism of action of long acting Vyvanse

Studies on Safety of Vyvanse medication: 

Coghill, D.R., Caballero, B., Sorooshian, S. et al. A Systematic Review of the Safety of Lisdexamfetamine Dimesylate. CNS Drugs 28, 497–511 (2014)

Clinical Studies on effectiveness of long acting stimulant medication for ADHD

These medicines are called stimulants because they increase the brain 

chemicals dopamine and norepinephrine.  

They are a central nervous system stimulant prescription medicine. 

These medications are Schedule 8 medicines which are subject to strict legislative controls due to their high potential for misuse, abuse and dependence. 

They come in 2 forms; long acting & short acting 

Long acting 

Takes from 45-90 mins to work

Lasts from 8-12 hours

One a day

Doses from 20mg to 70mg

This medication is Vyvanse

Vyvanse Patient Information 

Vyvanse Clinical Information 

Detailed medication data can be found here 

Covered on PBS $31.60 for 30 days

Short acting

Takes around 30 mins to work

Lasts from 3-4 hours

Multiple doses per day, upto a max of 8 tablets per day

5mg dose

This medication is Dexamphetamine 

Clinical trials highlighting effectiveness and safety

Long-lasting medicines are usually the most practical option because people with ADHD may have trouble remembering to take their medicine.

They also provide steady symptom relief throughout the day. By contrast, if you use short-acting stimulants, your symptoms may return between doses. Some people “crash” as their short-acting dose wears off, meaning their energy and mood drop.

Basal Ganglia

(Striatum: Caudate and Putamen) 

motivation, reward, and action regulation

Location: Deep subcortical structures near the centre of the brain.

• In ADHD, the brain’s reward system is more strongly driven by what feels interesting, urgent, or immediately engaging, rather than by what is important in the long term.

• This means tasks that are boring, repetitive, or have delayed rewards (e.g., paperwork, admin, long-term projects) can feel much harder to start and sustain, even when the person knows they matter.

• In contrast, tasks that are stimulating, novel, or time-pressured can be completed with high focus and energy.

• As a result, motivation can appear inconsistent—strong in some situations and very low in others—which is often misunderstood as laziness, but actually reflects how the brain processes reward and effort.

Primary functions

• Regulation of motor activity and restlessness
• Action selection and behavioural inhibition
• Habit formation and procedural learning
• Reward processing and reinforcement learning
• Filtering of competing stimuli and responses

Neurobiological basis::

• This system is highly dependent on dopaminergic signalling, particularly within fronto-striatal circuits
• Dopamine modulates the salience of rewards, effort allocation, and the initiation or suppression of behaviour

ADHD-related deficits

• Impaired behavioural inhibition and increased impulsivity
• Reduced capacity to sustain effort for tasks with delayed or abstract reward
• Heightened sensitivity to immediate reward, novelty, urgency, and stimulation
• Difficulty shifting behaviour in response to changing rules or contingencies
• Restlessness or a subjective sense of being internally “driven” to move

Structural and functional findings

• Neuroimaging studies frequently demonstrate reduced volume in basal ganglia structures, particularly the caudate nucleus, in individuals with ADHD
• Functional dysregulation within these circuits contributes to altered reward sensitivity and inefficient action selection

Location: Medial frontal brain region

Primary Functions

• Error monitoring (detecting mistakes and performance discrepancies)
• Conflict detection (identifying competing cognitive demands)
• Attention allocation (directing and sustaining focus)
• Motivation and effort regulation (modulating cognitive effort)
• Task switching (shifting between tasks and updating behaviour)

ADHD-Related Deficits

• Difficulty sustaining mental effort over time
• Reduced error monitoring and delayed behavioural adjustment
• Impaired attention maintenance, particularly for low-interest tasks
• Reduced persistence on cognitively demanding activities
• Difficulty shifting attention (cognitive inflexibility)
• Task paralysis or becoming “stuck” when initiating or transitioning between tasks
• Increased subjective cognitive fatigue, even with relatively simple tasks

Neurofunctional Context

The anterior cingulate cortex forms a core component of the frontostriatal executive control network, which is consistently implicated in ADHD. Dysfunction within this network contributes to impaired effort regulation, reduced cognitive control, and inefficient allocation of attentional resources.

Location: Distributed network including the medial prefrontal cortex and posterior cingulate cortex.

Primary functions

• Mind-wandering
• Internal mentation and self-referential thought
• Autobiographical memory

ADHD-related differences

• Increased and persistent mind-wandering
• Reduced ability to suppress internally generated thought during goal-directed tasks
• Attentional instability

In ADHD, the DMN shows reduced task-related deactivation, meaning it remains active during activities requiring sustained attention. 

This interferes with engagement of task-positive networks and contributes to distractibility and fluctuating focus.

Core Network Model of ADHD: 

ADHD is best understood as a disorder of network-level dysfunction across three interconnected systems:

1. Prefrontal executive control network
   → planning, inhibition, working memory
2. Frontostriatal reward network
   → motivation, reinforcement learning, reward sensitivity
3. Fronto-cerebellar timing network
   → timing, coordination, prediction, temporal processing

Disruption across these networks produces the core clinical features of ADHD:

• Attentional dysregulation
• Impulsivity
• Executive dysfunction
• Motivational dysregulation

Neurobiological integration:

ADHD does not arise from a single regional deficit. Rather, it reflects altered connectivity and communication between networks, particularly within dopaminergic pathways. Dopamine modulates signal-to-noise ratio in these circuits, influencing attention, motivation, and behavioural regulation.

When dopaminergic tone is optimal—such as during tasks that are novel, highly stimulating, or urgent—network efficiency improves. This can result in periods of intense, sustained focus and productivity (commonly described as hyperfocus).

Summary:

ADHD reflects differences in distributed brain systems responsible for:

• Executive functioning (planning, attention, self-regulation)
• Motivation and reward processing
• Emotional regulation
• Time perception and temporal organisation

These features arise from dynamic interactions between large-scale neural networks rather than isolated structural abnormalities.

Cerebellum: timing, coordination, and regulation

Location: Posterior brain structure beneath the occipital lobes.

Primary functions:

• Timing and sequencing of behaviour
• Motor coordination and balance
• Cognitive timing, prediction, and pacing of mental activity
• Attention modulation and regulation of mental effort
• Regulation of emotional and cognitive tempo

ADHD-related deficits:

• Impaired sense of time (“time blindness”)
• Difficulty estimating duration and sequencing tasks across time
• Feeling either rushed or “stuck” when initiating or progressing tasks
• Motor restlessness and coordination difficulties
• Reduced cognitive timing and prediction, impacting task planning and follow-through

Neuroimaging studies consistently demonstrate reduced cerebellar volume and delayed maturation in individuals with ADHD, contributing to impairments in temporal processing, coordination, and the regulation of cognitive and emotional pace.