Andrew Huberman talks about ADHD

1) Andrew discusses the brain networks involved in attention and how they can be expensive in terms of metabolic resources. He emphasizes the importance of the prefrontal cortex, located behind the forehead, in orchestrating neural circuits that control attention and focus. Attention is a complex process that involves suppressing unwanted noise in the background and attending to specific things. He explains that although attention is a powerful resource that allows us to navigate life with efficiency and adaptability, it can also make us feel tired and mentally drained, especially when we need to continuously attend to specific things.

2) Andrew discusses how the prefrontal cortex is responsible for attention and how it suppresses and enhances the activity of other brain networks. The prefrontal cortex's top-down inhibition is responsible for its ability to quiet other brain areas, hold back impulsive and distracting thoughts and impulses, and pay attention. ADHD is not due to the prefrontal cortex being deficient but is caused by its inability to properly communicate with other brain areas. As a result, background chatter becomes very loud, and the default mode network is often still active while trying to focus on external tasks, causing distractions, and a lack of focus.

3) The prefrontal cortex needs to coordinate with other tasks, making it inefficient at paying attention to what it wants. If the prefrontal cortex is overactive, the person cannot be efficient at paying attention, leading to laser focus on anything presented in front of them. Stimulants, such as Adderall, fall under the category of sympathomimetics. The activation of components in our nervous system very much resembles the sympathetic nervous system, which causes arousal, alertness, and focus. However, the prefrontal cortex needs to be flexible, pay attention to different tasks, go back to previous tasks, and adapt to different situations.

4) Adderall is a combination of amphetamine salts, specifically dextroamphetamine (D-amphetamine) and levoamphetamine (L-amphetamine). The D-amphetamine is the highly potent component and works mainly on receptors in the brain, whereas the L-amphetamine increases peripheral effects like blood pressure and heart rate. The major effect of Adderall and other stimulants is to increase the transmission of dopamine and norepinephrine, which are neuromodulators that increase or decrease the firing patterns of particular brain circuits, leading to increased motivation, pursuit, and mood.

5) Andrew discusses how drugs like Adderall increase dopamine and norepinephrine in the brain, which leads to an increase in motivation, focus, and alertness, and why these drugs are effective in treating ADHD. He explains synapses and the role neurotransmitters play in synaptic communication, and how the presynaptic terminal affects the amount of neurotransmitter that is released into the synapse.

6) Andrew explains that Adderall is a highly effective sympathomimetic drug that can increase dopamine and norepinephrine release, but its major effects come from its ability to increase dopamine to a greater extent than norepinephrine. The speaker also discusses Vyvanse, which is not an extended-release Adderall but rather a pro-drug containing only D-amphetamine in a time-release form that was developed to prevent abuse potential. Vyvanse has proved to be very effective in treating ADHD due to its time-release, which prevents abuse and makes it an optimal and vital probiotic for microbiotic health.

7) Andrew discusses the brain networks responsible for attention and executive function and how dopamine and norepinephrine impact these networks. They explain that dopamine acts as noise reduction, suppressing distracting signals from both external and internal sources within the brain. In contrast, norepinephrine serves to boost signals, increasing the frequency and amplitude of communication between neurons. He also notes that Adderall, Vyvanse, and Ritalin increase both dopamine and norepinephrine, which leads to a reduction in noise and an increased ability to focus and learn.

8) The success of such drugs in increasing focus and reducing hyperactivity and impulsivity depends on dosage, sensitivity, and stage of development across a lifespan. While dopamine and norepinephrine increase due to the drugs help reduce noise in the brain's networks, boosting the signal of the networks can also lead to euphoria, mania, and psychosis in some cases. It is worth noting that not everyone with ADHD exhibits impulsivity and hyperactivity; some just have challenges with focus.

9) Andrew discusses the reason why stimulants calm down kids with ADHD and how these drugs treat ADHD symptoms. The brains of children and adults with ADHD have all the networks functioning, but they tend to be hyper-connected, which increases synchrony between the networks. Giving a stimulant does not place a kid in a state of calm; rather, it tunes the amount of dopamine and norepinephrine present in specific brain networks, allowing the person to achieve just the right balance between the activation of neural circuits and reducing their synchrony. The goal of prescribing these drugs is to allow these networks to be activated to the right levels and in the right sequence. By analogy, dopamine and norepinephrine help the conductor activate instruments in the right order in order to create the right music.

10) Andrew discusses the use of ADHD medication in children and how it affects their neural circuits. While the use of these drugs is designed to improve the function of neural circuits that allow a child to focus, it's also intended to increase the strength of those circuits, which helps them learn what focus is. As such, in some cases, these drugs can be used and then withdrawn later as the circuits they help build are functioning well.

11) Andrew discusses the variation in dosage of ADHD medication among patients and the difficulty in predicting how an individual will react to a given dosage. While some patients may respond positively to extremely low dosages, others may require very high dosages to achieve relief of their ADHD symptoms. The main factor in the variation of effective dosages is the different enzymes or levels of enzymes that people have which metabolize the drugs. Unfortunately, there is no test that can predict how someone will respond to the medication.

12) Andrew discusses the long-term effects of ADHD medication on the body, particularly the risk of cardiovascular issues due to the elevated sympathetic nervous system activity caused by the medication. While studies have pointed towards a subtle increase in cardiovascular risk, there is no dramatic evidence that the drugs should be avoided. However, the importance of arriving at a minimal effective dosage and adopting practices that promote cardiovascular health is emphasized.

13) Huberman discusses the importance of timing and schedules in taking drugs for the treatment of ADHD, as different drugs have different time courses of action that can affect cortisol release and sleep. He explains that Ritalin is short-lived, making it attractive for morning and afternoon use without affecting sleep, while long-duration release drugs like Vyvanse might inhibit sleep. Adderall has a medium-duration release, making it a good option for some people to take early and later in the day with minimal impact on sleep.

14) Andrew discusses how chronic elevations of cortisol due to stress can lead to the suppression of total and/or free unbound forms of testosterone and estrogen, resulting in physical and psychological effects like reduced libido, muscle and bone mass. However, there is no evidence to suggest that taking medication for ADHD will lead to irregular ovulatory cycles or cessation of menstruation. The discussion then goes on to address concerns about whether children and adults who take ADHD medication are at a higher risk of addiction or predisposed to psychosis.

15) Andrew discusses the relationship between amphetamine-type ADHD drugs and the induction of psychosis. According to the speaker, all amphetamines and methylphenidate can cause psychosis. Factors such as having a first relative with schizophrenia or bipolar depression can predispose someone to psychotic episodes. There is a divided opinion or conflicting literature on whether if someone takes methylphenidate and experiences psychotic episodes, stopping the drug usually ceases the episode, whereas psychotic episodes resulting from taking Adderall can sometimes continue even after the person has stopped the drug.

16) Andrew discusses the abuse and addictive potential of Vyvanse and other drugs used to treat ADHD. Although there have been instances of patients trying to increase the rate of absorption of Vyvanse to achieve a high, it is associated with fewer psychotic episodes, abuse, and addictive potential overall. The kinetics or time course of dopamine and norepinephrine release caused by a drug is strongly correlated with its addiction potential and its potential to induce psychotic episodes. Methamphetamine is especially relevant since it increases dopamine so fast and then it drops below the baseline levels of dopamine initially present.

17) Andrew discusses the use of modafinil and armodafinil for ADHD, mentioning that while the drugs do increase levels of attention, they can also lead to negative side effects such as decreased appetite, headaches, and a rare but potentially fatal skin condition. He emphasizes the need for caution when considering which drugs to prescribe, especially for children. The last drug discussed in this section is guanfacine, which is a non-stimulant medication that only increases norepinephrine and is therefore less commonly prescribed for ADHD as it can make people feel very sleepy, although a small subset of individuals tolerate it well and experience relief from their symptoms.