May 29, 2023 • 1hr 58min

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

Huberman Lab

In this episode, Dr. Andrew Huberman provides a comprehensive overview of medications used to treat attention-deficit/hyperactivity disorder (ADHD), with a focus on stimulant medications like Adderall, Ritalin, and Vyvanse. He explains the underlying neurobiology of ADHD, how these medications work in the brain, their effects on cognition and behavior, potential risks and side effects, and considerations for long-term use. The discussion covers both childhood and adult ADHD treatment.

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Key Takeaways

ADHD involves challenges with executive function and attention regulation due to hyperconnectivity between brain networks that are normally more segregated
Stimulant medications like Adderall and Ritalin work by increasing dopamine and norepinephrine in the brain, which helps reduce "noise" and amplify relevant signals
These medications can induce neuroplasticity to strengthen attention circuits over time, potentially allowing some patients to eventually reduce or stop medication
Proper diagnosis and dosing is critical - there is huge individual variation in medication response and optimal dosage
When used as prescribed, stimulants do not appear to increase risk of substance abuse and may actually reduce this risk in ADHD patients
Long-term effects on growth, cardiovascular health, and other systems appear minimal when medications are used appropriately, but more research is still needed
Non-stimulant options like guanfacine work through different mechanisms and may be helpful for some patients who don't tolerate stimulants well
Combining behavioral therapies with medication tends to produce the best outcomes for managing ADHD symptoms

Introduction

In this episode, Dr. Andrew Huberman provides a comprehensive overview of medications used to treat attention-deficit/hyperactivity disorder (ADHD), with a focus on stimulant medications like Adderall, Ritalin, and Vyvanse. He explains the underlying neurobiology of ADHD, how these medications work in the brain, their effects on cognition and behavior, potential risks and side effects, and considerations for long-term use. The discussion covers both childhood and adult ADHD treatment.

Topics Discussed

Neurobiology of ADHD and How Stimulants Work (7:22)

ADHD involves challenges with executive function and regulating attention
The prefrontal cortex acts as an "orchestra conductor" to coordinate different brain networks
In ADHD, there is hyperconnectivity between networks that are normally more segregated
Stimulants increase dopamine and norepinephrine in the brain
- Dopamine helps reduce background "noise"
- Norepinephrine amplifies relevant signals
This improves the signal-to-noise ratio, enhancing focus and attention regulation

Specific Medications and Their Mechanisms (21:29)

Adderall contains a 3:1 ratio of d-amphetamine to l-amphetamine
- D-amphetamine has stronger central effects, l-amphetamine more peripheral effects
Vyvanse is a prodrug that slowly releases d-amphetamine (32:20)
- Designed to have lower abuse potential than Adderall
Ritalin (methylphenidate) works similarly but through slightly different mechanisms (36:36)
- Primarily increases dopamine rather than both dopamine and norepinephrine
All of these medications inhibit reuptake and increase release of dopamine/norepinephrine

Effects on Focus, Hyperactivity and Impulsivity (45:28)

Stimulants can reduce hyperactivity and impulsivity by improving executive function
They allow the prefrontal cortex to better coordinate and regulate other brain networks
This helps quiet overactive circuits and amplify relevant signals for improved attention
Proper dosing is critical - too high doses can lead to anxiety, euphoria, or even psychosis
There is huge individual variation in optimal dosage and medication response

Neuroplasticity and Long-Term Effects (54:48)

Stimulants can induce neuroplasticity in attention-related circuits
This may allow some patients to eventually reduce or stop medication
Long-term studies show better outcomes for those treated vs. untreated
Proper treatment does not appear to increase risk of substance abuse and may reduce this risk
Effects on growth, cardiovascular health appear minimal with appropriate use

Considerations for Children vs Adults (58:06)

Early treatment in childhood can help "train" attention circuits
Adult ADHD may require ongoing medication
Accurate diagnosis is critical before starting medication, especially in children
Combining behavioral therapies with medication produces best outcomes

Dosing, Duration, and Long-Term Use (1:05:12)

Wide range of effective doses - impossible to predict optimal dose
Short vs long-acting formulations have different pros/cons
Some advocate for "drug holidays" on weekends/vacations
Tapering off medication should be done carefully under medical supervision
Long-term studies mostly on Ritalin, less data on newer medications

Potential Side Effects and Risks (1:13:28)

Minimal effects on height/growth with appropriate use
Slight increase in cardiovascular risk, but benefits outweigh risks for most
Can increase cortisol, potentially impacting other hormones
Avoid combining with alcohol

Psychosis and Addiction Risk (1:27:45)

Small risk of triggering psychosis, especially in those predisposed
Amphetamines carry higher risk than methylphenidate
Methamphetamine is far more dangerous than prescription stimulants
Recreational/non-prescribed use carries much higher risks

Non-Stimulant Options (1:45:35)

Modafinil/armodafinil work through different mechanisms
- Can improve wakefulness and focus
- Not officially approved for ADHD but sometimes used off-label
Guanfacine is a non-stimulant option that affects norepinephrine (1:53:03)
- Can help some patients who don't tolerate stimulants well
- Sometimes combined with stimulants to offset side effects

Conclusion

Stimulant medications can be highly effective for managing ADHD symptoms when used appropriately under medical supervision. They work by increasing dopamine and norepinephrine to improve executive function and attention regulation. While there are some risks and side effects to consider, the benefits tend to outweigh the risks for most patients when medications are properly prescribed and monitored. Combining medication with behavioral therapies often produces the best outcomes. More research is still needed on the long-term effects of newer medications. Overall, these medications can significantly improve quality of life and functioning for many individuals struggling with ADHD.