Found a good series on ADHD stimulants and how to optimize their usage to minimize side effects:
Key actionable points from all 3 videos:
1. Use the Lowest Effective Dose
- Stay around 5 to 10 mg.
- Avoid dose escalation.
- Never chase euphoria.
2. Prefer Short-Acting Formulations
- Avoid extended release if it disrupts sleep or keeps adrenaline elevated.
- Let your nervous system fully reset each day.
3. Take Regular Off Days
- Use stimulants 4 to 5 days per week max.
- Take at least 2 consecutive days off.
- Preserve dopamine sensitivity.
4. Pair Medication With High-Value Work
- Only use during difficult, meaningful tasks.
- Do not pair with entertainment or low-value dopamine activities.
- Train focus so you eventually need less medication.
5. Enhance Dopamine Efficiency, Not Dose
- Consider strategies that prolong dopamine action rather than increase release.
- Avoid stacking multiple dopamine-releasing agents.
6. Address Other ADHD Mechanisms
- Investigate anxiety, glutamate excess, GABA imbalance, histamine, or cholinergic issues if dopamine targeting is insufficient.
7. Support Neural Health
- Avoid chronic sympathetic overdrive.
- Monitor cardiovascular stress.
- Protect sleep and circadian rhythm.
- The speaker argues that higher doses of amphetamine medications are not better and recommends keeping Adderall at a low dose (around 5 mg, never above about 10 mg) to avoid dopamine receptor downregulation and excessive sympathetic nervous system activation.
- He prefers dextroamphetamine-dominant formulations because they are more dopaminergic and less adrenergic than equal-salt generics, which may reduce stress and side effects.
- He stresses the importance of off days (several days per week without use) to maintain effectiveness and prevent tolerance.
- A core part of his “biohack” is to boost dopaminergic effects through receptor modulation rather than increasing the stimulant dose.
- To achieve this, he mentions sigma-1 receptor agonism (e.g., via certain supplements or drugs like DHEA, donepezil, fluvoxamine) to potentially enhance dopaminergic signaling without more amphetamine.
- He discusses monoamine oxidase B inhibitors, especially safinamide, as a way to prolong dopamine activity and reduce glutamatergic excitotoxicity, which he believes could make low-dose Adderall more effective and less damaging.
- Donepezil, due to its cholinergic and sigma-1 activity, is suggested as another agent to possibly augment focus and memory when paired with low-dose amphetamines.
- He touches on ghrelin receptor agonism (e.g., via MK-677) as another modulator of dopaminergic tone and mentions concerns about dopamine excitotoxicity, arguing that supporting plasticity and growth factors may mitigate long-term harm.
- Additional experimental points include blocking excitatory pathways (such as glutamate) and using angiotensin receptor blockers to limit vascular and neural stress.
- Overall, his approach frames stimulant use as a tool to accelerate learning and habituation, with an emphasis on maintaining sensitivity, protecting neurons, and enhancing dopamine efficiency rather than increasing dose.
- The creator frames ADHD not as a disease but as a behavioral and likely polygenic phenotype involving multiple neurotransmitter systems affecting focus, memory, and attention.
- Traditional treatments include cognitive behavioral therapy and stimulants. Stimulants like amphetamines and methylphenidate boost dopaminergic and adrenergic signaling to improve motivation and energy.
- The video’s author prefers short-acting stimulants over extended-release versions to avoid circadian disruption and long-term side effects on sleep and nervous system regulation.
- He recommends taking regular breaks from stimulant use (for example four to five days per week) to prevent tolerance from developing and reduce neurochemical down-regulation.
- ADHD symptoms can arise from multiple neurobiological mechanisms, including anxiety, excess glutamate, GABA dysregulation, and histamine or cholinergic signaling issues, meaning dopamine-focused treatment does not address all cases.
- The speaker discusses supplement and drug strategies targeting the cholinergic system, including acetylcholinesterase inhibitors and other agents thought to support memory and focus.
- He emphasizes careful dosing of stimulants, advocating for the lowest effective dose (for example around 5-10 mg) and warning against high doses that may harm neural health.
- Training while medicated should be purposeful: use periods of enhanced focus for valuable, difficult tasks rather than low-value activities to habituate productive behavior.
- The video asserts that long-term stimulant use, when managed responsibly, can lead to lasting improvements in focus and cognitive function even after discontinuation.
- Cardiovascular and stress-related side effects are a concern with long-term stimulant use, and lifestyle strategies or adjunctive medications may be needed to manage these effects.
- Dopamine drives motivation, reward, habit formation, focus, and ambition, but excessive stimulation can lead to addiction, tolerance, and receptor downregulation.
- The speaker warns that high daily stimulant doses, such as 50 to 70 mg of amphetamine, constitute misuse and increase long term neuroadaptation risk.
- Dopamine signaling can be manipulated at three main points: increasing release, blocking reuptake, and inhibiting enzymatic breakdown.
- Amphetamine increases dopamine release and also inhibits reuptake, but direct release is considered the most addictive and tolerance forming mechanism.
- Bupropion blocks the dopamine transporter, prolonging dopamine’s action without strongly increasing release.
- Safinamide inhibits MAO-B, slowing dopamine degradation in the extracellular space and modestly increasing dopamine tone.
- The proposed strategy is to use a low dose stimulant and enhance its effect through reuptake and degradation inhibition instead of escalating stimulant dosage.
- He recommends limiting stimulant use to about 4 to 5 days per week to reduce tolerance and preserve effectiveness.
- The overall goal is to maintain cognitive enhancement while minimizing receptor downregulation, addiction risk, and dose escalation.