No More Hangovers | Ft Leo and Longevity

This video features Leo (from Leo and Longevity) and Tony Huge discussing a comprehensive protocol for curing hangovers, breaking it down into multiple physiological pathways. They cover everything from sleep quality and dehydration to the often-overlooked withdrawal component of hangovers, along with pharmaceutical and natural supplement options. The conversation also detours into a broader discussion about responsible pharmacology use and cognitive enhancement.

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1. Introduction: The Multi-Pathway Approach to Hangovers

The video kicks off with Leo and Tony Huge (who calls himself "your tour guide to the dark side of biohacking") laying out the premise: hangovers can be addressed through hard pharmaceutical approaches or through natural supplements. They decide to go through the full protocol, starting with the strongest options and working through all the different mechanisms that cause a hangover.

Leo identifies four main pathways that contribute to a hangover:

• Poor sleep quality from the night of drinking
• Dehydration and electrolyte depletion
• GABAergic withdrawal (the body's rebound from alcohol's calming effects)
• Elevated blood pressure and heart rate
• Plus a bonus fifth pathway: oxidative stress in the brain

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2. Sleep Quality: Why "Passing Out" Isn't Real Sleep 😴

The first thing Leo addresses is something most people don't think about — when you go out drinking, your sleep that night is completely ruined. Even though people feel like they're "passing out" and sleeping deeply, they're actually not getting quality restorative rest.

"People pass out, they look like they're sleeping, but they're not getting quality regenerative sleep. They keep waking up."

He explains that sleep has two critical phases: non-REM deep sleep and REM sleep (the dreaming phase). Alcohol particularly damages REM sleep. His recommendation? If you want to use a sleep aid, don't use anything that works through the GABA system — no Z-drugs like Ambien — because alcohol already works through that same system, and stacking them would be counterproductive (or dangerous).

Instead, Leo suggests a simpler approach: melatonin. It dramatically improves REM sleep specifically. He also mentions cholinergic drugs like donepezil, but melatonin is the accessible, easy recommendation for most people.

"If you take melatonin, melatonin dramatically improves REM sleep specifically."

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3. Dehydration and Electrolytes: The Basics Most People Know 💧

This section covers the more commonly known aspect of hangovers — dehydration and electrolyte loss. When you drink alcohol, your body flushes out key minerals, so you want to replenish:

• Magnesium
• Potassium
• Calcium
• Or simply grab a Gatorade (which covers multiple electrolytes)
• Plus plenty of water

Tony Huge chimes in here, noting that his own limited hangover experiences were primarily due to dehydration, especially from dancing and drinking without replenishing fluids and electrolytes simultaneously.

"For me, I've never really had a full hangover. I've had like maybe a very slight — like I kind of think I know what it feels like but I'm not sure."

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4. The Withdrawal Component: The Hidden Cause of Hangovers 🧠

This is where the conversation gets really interesting and dives into territory most people aren't aware of. Leo shares from personal experience — in his early 20s, he was a daily drinker while working in private equity, and he started noticing something alarming:

"In the mornings I would have a bit of a shake, a bit of a tremor, like a real alcoholic. I didn't know what it meant."

Years later, he discovered that the majority of the hangover experience mentally is actually hypo-GABAergic signaling — meaning low GABA activity the next day. Here's the mechanism: alcohol is an inhibitory drug that calms the nervous system down through the GABA system. Even after just one night of drinking, your body begins adapting. The next day, when the alcohol is gone, your GABA signaling is suppressed, leaving you in a mild withdrawal state.

"Even in that one night, your body actually already gets used to it. The next day, even if you don't feel the shakes, you're having that low GABA signal."

This explains a common phenomenon that many people have experienced: the "hair of the dog" cure. Having a mimosa at Sunday brunch after a Saturday night out genuinely makes you feel better — not because of magic, but because you're re-introducing the substance your body is withdrawing from.

"I discovered — wait a minute, if you have like on a Saturday brunch... once you had a couple drinks, you're like, wait a minute, the hangover was gone."

Pharmaceutical Options for Addressing Withdrawal

Leo explains that if you were to take 0.5 to 1 milligram of Xanax the next morning (hypothetically), the hangover symptoms would largely vanish. But he strongly cautions against this:

"I'm not recommending it because some people will become addicted to the benzo, and if you God forbid are addicted to the alcohol and you start using a benzo every time, you could really end up with seizures and serious problems."

He frames it as something a traveling businessman might consider in a pinch — if you had one too many drinks and have an important meeting the next morning. But always:

"You always start with the smallest amount, wait a half hour or so, one hour, and then see if you need more. Because you only want to just remove the edge — you don't want to then get used to this thing, because at some point your body has to re-up-regulate the GABA system."

Safer Alternatives for the GABA Withdrawal

Rather than reaching for addictive benzodiazepines, Leo recommends safer GABAergic options:

• L-theanine (found in green tea, very safe)
• Valerian root extract
• Gabapentin (a prescription medication but less addictive than benzos)
• Pregabalin (a muscle tranquilizer-type drug, also less addictive)

He notes that some other drugs he likes, such as sodium valproate or oxcarbazepine, won't work here because they take days to build up in your system — you need something that acts quickly for an acute hangover.

"I just warn people from using these strongly addictive benzos or GABAergic drugs. I would rather use something like Gabapentin combined with L-theanine."

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5. Blood Pressure and Heart Rate: The Hidden Cardiovascular Impact ❤️‍🔥

This is another underappreciated consequence of drinking that Leo highlights. If you go out drinking on a Friday night and check your blood pressure and heart rate the next morning, you'll find them abnormally elevated.

"If you are somebody prone to high blood pressure like myself, you will find it significantly elevated. Like mine used to be sometimes 180 over something the next morning, even though the average was 140 or so — which was also not good."

For someone who drinks even just once a week, this means you're experiencing an episode of acute hypertension every single week, which adds up over time and can seriously affect long-term cardiovascular health.

His protocol for this involves:

• Nebivolol (a beta-blocker): about 5 milligrams the next morning if your heart rate is elevated
• Telmisartan (an ARB blood pressure medication): about 20-40 milligrams if you don't normally have hypertension

"The point would be just to not have that acute hypertension the next day, which affects your health seriously. If you go out drinking once a week, this will affect your health long term."

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6. Oxidative Stress: The Brain Fog Protocol 🌫️

Leo adds one more pathway he almost forgot — oxidative stress. After a night of drinking, your body is loaded with oxidative damage. While the liver processing isn't what gives you the hangover feeling, oxidative stress in the brain triggers your immune system to try to neutralize it. The problem? The immune system sometimes over-repairs and does additional damage.

His solution is what he calls his "hydrophilic anti-inflammatory stack":

• 1 gram of NAC (N-Acetyl Cysteine)
• 1 gram of Vitamin C
• 1-3 grams of EPA (from omega-3/fish oil)
• 1-3 grams of tributyrin
• 500 milligrams of astaxanthin (ASTA or ATKA)

He suggests taking this twice that day, but even just the morning dose makes a noticeable difference:

"If you do it in the morning, you'll notice the brain fog uplifts slightly. You really will notice it."

"If you do all of these things, you have the best response possible."

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7. The Digression: Pharmacology, Stigma, and Cognitive Enhancement 💊🧪

The latter part of the video shifts into a broader conversation about the stigma around responsible drug use. Tony Huge points out that despite never having been drunk in his life, people online label him a "drug addict" simply because he discusses pharmacology openly.

Leo gets passionate about this topic, sharing that online haters have called him a drug addict despite his actual usage being quite modest:

"I was not even using hedonistic drugs. Not drinking. I would smoke weed once every two weeks. I used amphetamine at five milligrams four days a week. But because I mentioned different pharmacology, they conclude — oh, he's a drug addict."

He contrasts this with historical figures in the bodybuilding/chemistry world, like Dan Duchaine, who was reportedly using 100 milligrams of Valium a day for years without receiving the same criticism.

Tony attributes this double standard to the "natty movement" — a culture where influencers lie about what they take, creating unrealistic expectations and making the public hostile toward anyone who's transparent about their use of performance-enhancing substances.

"All these successful people, whatever they're successful at, are using drugs to get there. And that information starts leaking out, and then you have this group of people that want to deny it."

Leo's Personal Story: From Average to Exceptional Through Pharmacology

Leo shares a deeply personal story about his cognitive journey. He openly admits:

"I was not born intellectually gifted at all. I'm not smart. I'm quite average."

He got into Carnegie Mellon largely through a strategic shotgun approach — applying to around 30 top schools despite his high school counselor telling him he wouldn't get into any. He failed his math classes in the first year.

"They were very nerdy at the school. I was sort of accepted by accident and I shouldn't have been there, really."

What transformed him was a combination of three things: pharmacology (specifically low-dose amphetamines), extreme hard work, and sacrifice. He describes his college living situation:

"I didn't have a bed in college. I didn't have a couch. My office was in the bedroom. I would sleep on the living room floor. Everything was white. I forced myself to work."

He explains that amphetamines didn't just help him focus — they made his brain plastic and helped him enjoy subjects he previously hated:

"The dopamine made me like stuff I didn't like — like math. I was studying it happy because I'm taking it, and also my brain was very plastic. I changed dramatically."

Looking back, he says if he could redo college, he would use even more tools — not just amphetamines, but also things for neurogenesis, plus supplements like L-tyrosine and uridine monophosphate to reduce the amphetamine dose needed. He'd also never use a long-acting formulation and would limit usage to four days a week.

"All these kind of lessons I learned through my own mistakes — I try to communicate on my channel to prevent other people from going through what I went through."

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Wrapping Up

This video provides a surprisingly thorough, science-based breakdown of hangovers that goes far beyond the typical "drink water and eat greasy food" advice. The key takeaway is that hangovers are multi-factorial — they involve disrupted sleep, dehydration, electrolyte depletion, GABAergic withdrawal, cardiovascular stress, and oxidative damage — and the most effective approach addresses all of these pathways simultaneously.

The complete hangover protocol summarized:

1. 🛏️ Take melatonin before bed to protect REM sleep
2. 💧 Rehydrate with water and replenish electrolytes (magnesium, potassium, calcium, or Gatorade)
3. 🧠 Address GABA withdrawal with safe options like L-theanine, valerian root, or gabapentin (avoid benzos)
4. ❤️ Monitor and manage blood pressure/heart rate with appropriate medications if needed
5. 🧪 Combat oxidative stress with NAC, Vitamin C, EPA, tributyrin, and astaxanthin

As always, start with the lowest effective dose of anything, and consult a healthcare professional before taking pharmaceutical interventions. And as Leo emphasizes — the goal is responsible, informed use, not dependency.