Adderall, Stimulants & Modafinil for ADHD: Short- & Long-​​Term Effects

Stimulants for ADHD Treatment

• ADHD treatments focus on improving attention and focus 
  • Attention involves suppressing background noise and focusing on specific tasks
  • Prefrontal cortex plays a crucial role in attention and focus
• People with ADHD have difficulty orchestrating activity in other brain networks 
  • Prefrontal cortex sends inhibitory signals to suppress other brain areas

ADHD Medications

• Adderall, Ritalin, Vivance, Modafinil, Rmodafinil, and Guanfacine 
  • Improve symptoms of ADHD
  • Commonly used without prescription for focus and recreational purposes
  • Up to 80% of college-​​age young adults have used these drugs at some point
• Risks of using these drugs without prescription 
  • Black market drugs may be contaminated with fentanyl, which is deadly

How ADHD Medications Work

• Stimulant medications increase activity in the prefrontal cortex 
  • This helps suppress other brain areas and improve focus
• Common questions about ADHD medications: 
  • Are they similar to methamphetamine?
  • What is their addictive potential?
  • Can they cause psychotic symptoms?
  • What are the long-​​term consequences of taking them?

Effects of ADHD Medications

• Impact on sleep, hormone health, reproductive health, and height 
  • Some studies suggest ADHD meds may restrict height in children
• Potential for addiction to other substances 
  • Research is ongoing to determine if ADHD meds predispose individuals to addiction

Drugs for ADHD

• Most drugs for ADHD are stimulants or sympathomimetics 
  • Trigger the release of neurochemicals and activation of components of the nervous system
  • Resemble the activation of the sympathetic nervous system (alertness and arousal)
• Methamphetamine: potent sympathomimetic, high abuse potential, rarely prescribed for ADHD
• Adderall and Vivance: commonly prescribed for ADHD, similar to methamphetamine but less potent 
  • Adderall: combination of amphetamine salts (3:1 ratio of D‑amphetamine to L‑amphetamine)
    • L‑amphetamine less potent in increasing certain neurochemicals in the brain than D‑amphetamine
      Amphetamines and Adderall
• Dmphetamine: potent, mainly works on receptors in the brain 
• Lmphetamine: less potent, increases blood pressure and heart rate (peripheral effects)
• Adderall: combination of Dmphetamine and Lmphetamine 
  • Increases activity of two neurochemicals: dopamine and norepinephrine (noradrenaline)
    • Dopamine: increases motivation, pursuit, and mood
    • Norepinephrine: increases attention and focus
  • Effective in treating ADHD due to increased motivation, focus, and alertness

How Adderall Works

• Increases dopamine and norepinephrine by disrupting presynaptic transporters 
  • More neurotransmitters stick around and bind to receptors on the postsynaptic cell
• Disrupts the packaging of dopamine and norepinephrine into vesicles 
  • Buildup of neurotransmitters in the presynaptic terminal, leading to increased release and transmission
• Adderall’s major effects come from its ability to increase dopamine to a great extent

Vivance

• Not extended-​​release Adderall, but time-​​release Dmphetamine
• Contains only Dmphetamine, attached to an amino acid called Lysine 
  • Lysine is slowly cleaved off over time, making it a prodrug
• Developed to prevent abuse potential of Adderall and other drugs containing Dmphetamine
• Vivance is time-​​release dexadrine, not time-​​release Adderall
  ADHD Medications and Their Effects
• Vivance (time-​​release dexadrine) is effective in treating ADHD 
  • Slow absorption prevents abuse
  • Effects last 12–18 hours depending on metabolism
• Adderall has a quicker time course (6–8 hours) 
  • Some people prefer this, others find it too stimulating
• Ritalin (methylphenidate) was commonly prescribed for ADHD in the past 
  • Not as popular now due to the rise of Adderall and Vivance
  • Increases dopamine and norepinephrine, but not as potent as Adderall or Vivance
  • Shorter half-​​life (4–6 hours)

Dopamine, Norepinephrine, and Attention

• Dopamine helps with noise reduction in the brain 
  • Quiets background distractions (external and internal)
• Norepinephrine boosts signals at synapses 
  • Increases communication between neurons
• ADHD medications increase dopamine and norepinephrine 
  • Result in noise reduction and signal amplification
  • Lead to increased focus and reduced hyperactivity/​​impulsivity

Potential Issues with ADHD Medications

• Finding the right dosage and medication can be challenging

  • Varies based on individual sensitivity and stage of development
  • Too much dopamine can cause issues with focus and attention
  • Proper balance of dopamine and norepinephrine is crucial for effective treatment
    ADHD and Stimulants
• ADHD: challenges in focusing, impulsivity, and hyperactivity 
  • Not a one-​​size-​​fits-​​all condition; different patterns and symptoms
• Stimulants (e.g., Adderall, Vivance, Ritalin) used to treat ADHD 
  • Increase dopamine and norepinephrine levels
  • Tune the amount of these neuromodulators in the brain
  • Help balance activation of different neural circuits
• ADHD not just a deficiency in dopamine or norepinephrine 
  • Brains of those with ADHD have hyperconnected networks
  • Goal of stimulant treatment: adjust dosage and timing to allow proper neural circuit function

Neuroplasticity and ADHD Treatment

• Neuroplasticity: the brain’s ability to change in response to experience 
  • Strongly activating certain brain networks can induce neuroplasticity
  • Dramatic elevation in dopamine and norepinephrine promotes neuroplasticity at specific synapses
• Neuromodulators (e.g., dopamine, norepinephrine) vs. neurotransmitters 
  • Neuromodulators modulate the activity of neurotransmitters
  • Increasing neuromodulators strengthens connections and makes them more easily activated
• Original purpose of prescribing stimulants for ADHD: help focus and reduce hyperactivit 
  • Also aimed at promoting neuroplasticity during development
    ADHD Medication and Neuroplasticity
• ADHD medications designed to help brain networks responsible for focus undergo neuroplasticity 
  • Strengthen synapses involved for more efficient functioning later on, even after cessation of the drug
• Important for parents and children to consider when deciding to start or stop ADHD medications

Benefits of ADHD Medication

• Children with ADHD who are treated with appropriate doses of drugs like Adderall, Ritalin, or Vyvanse fare better in childhood and later in life 
  • Improved performance in school and focus
  • Lower risk of illicit drug use and addiction in adulthood
• Early treatment with ADHD medications leads to increased dopamine transmission in the forebrain later in life 
  • Normalization of neural circuits over time

Importance of Accurate ADHD Diagnosis

• A well-​​qualified psychiatrist will: 
  • Conduct a careful diagnostic evaluation
  • Prescribe appropriate pharmacologic treatments
  • Be aware of and prescribe behavioral treatments
  • Provide nutritional guidelines and supplementation recommendations
  • Update treatments as the child matures

Tapering Off ADHD Medication

• For individuals 25 years or younger who have taken ADHD medications, it may be beneficial to discuss tapering off the drugs with their psychiatrist 
  • Tapering should be done gradually to avoid withdrawal symptoms
  • Reductions in dosage over time may be optimal for some patients

Dosage Ranges for ADHD Medications

• Dosage ranges vary widely in studies and among individuals 
  • Adderall: 10–40 mg per day
  • Ritalin: 10–60 mg per day
  • Vyvanse: dosages in the hundreds of milligrams (due to the presence of Lysine)
• Dosage should be determined on an individual basis in consultation with a board-​​certified psychiatrist
  ADHD Medications: Dosage and Effects
• Difficult to predict how individuals will react to dosages of ADHD medications 
  • Example: 300-​​pound male finds relief with 2.5 mg of Adderall, while two sisters (120–140 pounds) need 180–240 mg for relief
• Psychiatrists assess dosage based on positive benefits and side effects
• Variation in dosage response may be due to genetic differences in enzymes that metabolize drugs in the brain and body
• No simple test to predict drug response; best approach is to start with the lowest effective dose and increase as necessary

ADHD Medications and Growth

• Concerns about long-​​term effects of ADHD medications on height, growth, and development
• No clear evidence that treatment with sympathomimetics during development limits overall height
• Children with ADHD treated with ADHD meds may have slightly higher BMIs compared to age-​​matched peers
• Long-​​term elevations of sympathetic nervous system activity carry some cardiovascular risk 
  • One study showed a subtle increase in cardiovascular risk, but not enough to discourage the use of ADHD medications

ADHD Medications and Alcohol

• Combining alcohol with sympathomimetics (e.g., Adderall, Ritalin) is more detrimental to the brain and body than taking the drugs alone
• Avoid alcohol consumption while taking ADHD medications

ADHD Medications and Hormone Systems

• Few studies on the long-​​term effects of ADHD medications on endocrine or hormone systems
• Long-​​term increase in sympathetic nervous system activity likely increases cortisol levels
• Timing and schedules of taking ADHD medications should be considered to avoid disrupting sleep and cortisol release patterns
• Short-​​acting drugs like Ritalin may be more attractive for managing sleep and cortisol release
  ADHD Medications and Their Effects
• ADHD medications can inhibit sleep 
  • Long duration release of d‑amphetamine (Vivance) can cause trouble falling asleep
  • Adderall has an intermediate time course of action between Ritalin and Vivance
• Cortisol is a hormone that can enhance focus and alertness 
  • High cortisol release early in the day is advantageous
  • Late day elevations in cortisol are correlated with depressive symptoms
• Sympathomimetic drugs can disrupt the endocrine system 
  • Chronic elevations in cortisol can suppress testosterone and estrogen levels
  • This can lead to reductions in libido, muscle and bone mass, and other aspects of testosterone-​​related psychology and bodily biology
• ADHD medications and addiction 
  • Appropriate treatment for ADHD reduces the risk of forming addictions to other substances
  • It is unclear whether individuals become addicted to ADHD medications themselves
• ADHD medications and psychosis 
  • Amphetamines and methylphenidate (Ritalin) can induce psychosis
  • Having a first relative with schizophrenia or bipolar disorder increases the likelihood of psychotic episodes when taking sympathomimetic drugs
  • Psychotic episodes often cease after stopping methylphenidate (Ritalin)
  • Long-​​lasting psychotic episodes can occur after taking Adderall, even after cessation of the drug
  • Potently increasing dopamine in a person with a predisposition to psychotic episodes can shift the system toward greater propensity for psychosis
• Methamphetamine
  • Considered an illicit drug and responsible for many negative health effects
  • Neurotoxic to serotonergic neurons, killing serotonin neurons
    Methamphetamine and ADHD Drugs
• Methamphetamine is a dangerous drug 
  • Kills dopaminergic neurons
  • High abuse potential, addictive potential
  • Can spark psychosis in predisposed individuals and create psychosis in others
• Prescription methamphetamine has extremely narrow clinical uses
• ADHD drugs of the amphetamine variety (e.g., Adderall, Dexedrine) have a higher likelihood of inducing psychosis in predisposed individuals 
  • Appropriately prescribed and safe dosages still have a low incidence of psychosis
• Methylphenidate (Ritalin) has a lower potential for inducing psychosis compared to amphetamine-​​type ADHD drugs
• Vyvanse (long-​​release d‑amphetamine) has fewer psychotic episodes and less abuse/​​addictive potential 
  • Not perfectly safe, but highlights the importance of dopamine and norepinephrine release kinetics

Dopamine Kinetics and ADHD Drugs

• Dopamine kinetics are crucial for understanding addiction and abuse potential 
  • Fast increase and decrease in dopamine levels are associated with higher potential for addiction and psychotic episodes
• Vyvanse has a long, extended release of dopamine and norepinephrine, reducing its overall abuse potential 
  • Does not create immediate euphoria and crash below baseline
• Recreational and off-​​prescription use of ADHD drugs can lead to addiction and higher potential for psychotic episodes 
  • First-​​time users experience large increases in dopamine, leading to euphoria and heightened focus
• Repeated use of ADHD drugs leads to lesser peaks in dopamine each time 
  • Homeostatic plasticity and habituation to the drug

ADHD Drug Usage Patterns

• Original clinical literature suggested that ADHD drugs should not be taken every single day 
  • Designed for use during the school week with weekends off or during the school year with summer breaks
• Different biological and neuroplastic responses to taking a drug once, taking a drug for five days with weekends off, and taking a drug every day for years
• Long-​​term effects of ADHD drugs are still being studied, with most literature focusing on methylphenidate (Ritalin)
  Long-​​Term Effects of ADHD Medication
• Focus on methylphenidate (Ritalin) due to its history as the first drug used to treat ADHD 
• Studies have shown improvement in executive function in kids and adults who have taken ADHD meds for months to years
• Limited data on long-​​term effects of other drugs like Adderall and Vivance

Non-​​Amphetamine Treatments for ADHD

• Modafinil (Provigil) and Armodafinil (Nuvigil) are non-​​amphetamine treatments for ADHD
• Used to treat daytime sleepiness issues related to narcolepsy, dementia, post-​​surgery anesthesia, traumatic head injury, and stroke
• Side effects can include decreased appetite, runny nose, headache, and skin rashes
• Stevens-​​Johnson Syndrome, a rare and potentially fatal skin condition, has been associated with Modafinil use

Atypical ADHD Treatments

• Bupropion (Wellbutrin) and Guanfacine are considered atypical treatments for ADHD
• Guanfacine is a non-​​stimulant medication that works on the noradrenergic system by stimulating the alpha-​​2A receptor
• Developed to lower blood pressure, Guanfacine can make some people feel sleepy but has been effective in a small subset of individuals with ADHD
• Guanfacine activates prefrontal cortical networks, increasing salience and relevance of stimuli for better attention
  Guamphacine in ADHD Treatment
• Approved for adults and primarily used in kids aged 6–17 years old 
• Improves executive function, increases coordinated firing of locus ceruleus neurons with prefrontal cortex
• Helps brain circuits learn how to focus, attend to certain things, and limit impulsivity and hyperactivity
• Sometimes prescribed in conjunction with other ADHD meds (e.g., Adderall, Vivance)
• Concerns about polypharmacology and drug cocktails
• Can have a profound effect on lowering tolerance for alcohol, leading to serious problems or even death

General Themes of ADHD Compounds

• Increase overall levels of arousal and wakefulness
• Lead to decreased levels of hyperactivity, impulsivity, and improved focus
• Act on neuromodulator systems like dopamine and norepinephrine
• Effective in creating neuroplasticity and changing the strength of connections in neural circuits
• Examples: Methylphenidate, Adderall, Vivance, Modafinil, R‑Modafinil, Guanphacine, Wellbutrin

Short and Long Term Effects of ADHD Compounds

• Immediate and long-​​term benefits and risks
• Risks of abuse, addiction, and psychotic episodes when taken recreationally
• Risks associated with long-​​term use in people with ADHD
• Importance of combining drug treatments and behavioral protocols for optimal results
• Working with a board-​​certified psychiatrist knowledgeable about ADHD and up-​​to-​​date on scientific and clinical literature