The Enhanced Brain: The Hidden Neurovascular Cost of Extreme Performance-Enhancing Drugs

The concept of the Enhanced Games has forced a quiet conversation into the open light. For decades, performance-enhancing drugs (PEDs) were used in the shadows, their dosages guided by locker-room lore and underground manuals. Athletes, teams, or whole countries are occasionally caught red-handed, such as when Russia’s Olympic doping scandal was exposed in 2014 (The Guardian, 2014). 

The Enhanced Games, a mini-Olympics with the “restrictions” of anti-doping policies stripped away, asked the question: What is the human body truly capable of? Athletes competed in Las Vegas, the home of sports venture capitalism, having followed semi-standardised regimens of chemical enhancement. These PED cocktails saw 91% of athletes taking additional testosterone,  29% on anabolic steroid agents, 79% using human growth hormone, 62% taking stimulants, and 41% using erythropoietin (EPO).

What each of these drugs do:

• Testosterone (91%) & Anabolic Steroids (29%)

  • Performance Benefit: Increases muscle protein synthesis, accelerates recovery, and maximises strength.
  • Mechanism: Binds to androgen receptors to upregulate anabolic pathways.
  • Health Risk: Left ventricular hypertrophy, high blood pressure, and hypogonadism.
  • Neurovascular Impact: Induces excess oxidative stress and endothelial dysfunction, accelerating brain accumulation of β-amyloid (Kaufman et al., 2019).

• Human Growth Hormone (79%)

  • Performance Benefit: Accelerates tissue repair, lipolysis, and collagen synthesis.
  • Mechanism: Stimulates the release of IGF-1 to promote cellular growth.
  • Health Risk: Insulin resistance, fluid retention, and acromegaly-like features.
  • Neurovascular Impact: Positives: promotes the formation of new blood vessels and neurons, and synaptic plasticity (Sanchez-Bezanilla et al., 2020a; Sanchez-Bezanilla et al., 2020b). Harms: increased pressure in the skull leading to migraines and vision impairment.

• Stimulants (62%) E.g. Adderall

  • Performance Benefit: Enhances focus, reaction time, and short-term power output.
  • Mechanism: Increases synaptic dopamine and norepinephrine concentrations.
  • Health Risk: Elevated heart rate and blood pressure, potential for life-threatening arrhythmias.
  • Neurovascular Impact: Causes blood-brain barrier dysfunction, profound neuroinflammation, and reductions in brain blood flow (Kousik et al., 2012; Sajja et al., 2015).

• Erythropoietin (41%)

  • Performance Benefit: Dramatically augments maximal oxygen uptake and endurance.
  • Mechanism: Stimulates erythroid progenitor cells to increase red blood cell (erythrocyte) mass. This is the same principle as high-altitude training.
  • Health Risk: Blood becomes excessively thick, elevating the risk of clots and stroke.
  • Neurovascular Impact: Excessively thick blood, increasing resistance to blood flow and limiting brain oxygen delivery (Robach et al., 2008; Schuler et al., 2009).

In sport science, we frequently discuss the obvious benefits: unprecedented muscle growth, elevated red blood cell counts, and immense explosive power. We also frequently discuss the well-documented peripheral risks, such as stress placed on the liver or testicular atrophy (shrinking)

However, the frontiers of modern neuroscience and vascular biology reveal a far more complex and troubling narrative. The human brain is not a passive bystander to extreme chemical enhancement. It is highly sensitive to ‘supraphysiological’ (far above natural) hormone levels, altered blood rheology, and fluctuating levels of artificial neurotransmitters.

In this post, we’ll look into some of the underlying physiological mechanisms on which these chemical cocktails work and how playing God with these systems can have catastrophic effects elsewhere in the body. In particular, we’ll look at the effects of these substances on the brain and its blood supply.

1. The Neurovascular Unit

Every breath you take and every thought you have relies on perfect teamwork between your brain cells and the blood vessels that feed them oxygen and glucose. This ‘team’ is called the neurovascular unit. It is made up of neurons (brain cells), the cells lining your blood vessels, smooth muscle cells that control blood flow, and special support cells called astrocytes. Extreme PED use is like pulling the bottom block out of a Jenga tower; the whole system becomes incredibly unstable.

Nitric Oxide and Flexible Blood Vessels 

Nitric oxide (NO) is your body's natural chemical for opening up (dilating) your blood vessels. Normally, when you exercise, the increased blood flow ‘rubs’ against the walls of your vessel (this is called shear stress) and triggers the release of NO. This relaxes the blood vessels, allowing more glucose and oxygenated blood to reach your muscles and brain.

However, huge doses of anabolic steroids and testosterone impair this process. Long-term steroid use damages the lining of the blood vessels (de Souza, 2019), lowering the amount of NO available. Without enough nitric oxide, your blood vessels become stiff and permanently narrowed. This means when an athlete pushes themselves to the absolute limit, their blood vessels cannot open wide enough to handle the massive pumping of the heart.On the note of nitric oxide (though not PED-related), previous research from our lab has identified reduced availability of nitric oxide in retired rugby players, compared to healthy non-players of the same age and fitness (Owens et al., 2023). 

Directing Blood Flow and Managing Carbon Dioxide 

Your brain is brilliant at sending blood exactly where it is needed. When a specific part of your brain works hard, it signals the local blood vessels to open up almost immediately.

But when steroid use damages the blood vessels and lowers NO levels, this system fails. The brain can no longer precisely direct blood to the areas working the hardest during intense physical or mental effort.

To make matters worse, healthy brain blood vessels are extremely sensitive to carbon dioxide (CO2). If carbon dioxide levels rise, the vessels open wide to flush it out; if levels drop, they narrow. Chronic steroid use may blunt this sensitivity through the manipulated hormone levels and their known influences on blood vessel constriction (tightening) and dilation (widening; Krause et al., 2006). When the brain loses its main defence mechanism against sudden changes in blood pressure or gas levels, it becomes vulnerable to tiny bleeds or a lack of oxygen (hypoxia).

2. The Brain's Plumbing System

One of the most profound recent discoveries in neuroscience is the glymphatic system. Think of it as the brain's internal plumbing or power washing network. Your brain produces a lot of metabolic waste, but it does not have a normal waste removal system like the rest of the body (the lymphatic system). Instead, it uses this bespoke network to flush out toxic proteins.

How the Wash Cycle Fails 

The glymphatic system uses cerebrospinal fluid (the clear fluid around your brain and spine) to wash away metabolic rubbish. This flow is driven by the rhythmic pumping of your brain's arteries and relies on special water channels in your astrocyte cells.

Huge doses of steroids and heavy stimulant use damage this delicate plumbing in a few ways:

• Astrocyte Damage: Chronic PED use scars the astrocyte cells (Acaz-Fonseca, 2016), impairing the fluid channels and blocking the flow of the cleaning fluid.

• Stiff Arteries: As mentioned earlier, steroids make arteries stiff. Since the pumping of flexible arteries drives this wash cycle, stiff arteries mean a weaker power wash.

When the plumbing fails, toxic waste builds up. The two main culprits are proteins called amyloid beta and tau. These are the same proteins that build up in diseases like Alzheimer's. Research shows that massive steroid use messes with how the brain creates and clears these proteins (Kaufman et al., 2019). With the waste removal system down, these toxic proteins clump together in the brain, setting the stage for major memory and cognitive issues down the road.

3. Rewiring the Brain: Structure and Insulation

The human brain is amazing at adapting, but flooding it with unnatural chemicals forces it to adapt in very negative ways.

Shrinking Brain Regions 

Brain scans of long-term steroid users show some worrying trends. They often have significant thinning in the outer layer of the brain, especially in the frontal and temporal lobes (Bjørnebekk et al., 2016). These are the areas responsible for decision-making, memory, and regulating emotions (hence the classic “roid rage” common among steroid users). Furthermore, the amygdala and hippocampus (the brain's emotional and memory centres, respectively) can actually shrink and stop communicating properly.

Frying the Wires 

The heavy use of stimulants like Adderall by many enhanced athletes massively disrupts brain chemistry. These drugs flood the brain with feel-good, high-energy chemicals like dopamine. Over time, the brain tries to protect itself by shutting down its receptors. This leaves the athlete completely depleted and burnt out when the drugs wear off.

At the same time, high testosterone levels damage the brain's electrical wiring. Your brain cells have a protective coating called myelin, acting like the plastic insulation on a copper wire. While normal testosterone helps maintain this, extreme super doses actually kill the cells (oligodendrocytes) that produce and install this insulation. This slows down the brain's electrical signals and permanently damages complex thought processes.

4. Heart Health and Thick Blood

While the brain changes happen quietly over years, the effects on the heart and blood vessels are immediate and life-threatening. Mixing testosterone, stimulants, and EPO creates a perfect storm for heart attacks and strokes.

Athletes use EPO (a naturally produced hormone) to make more red blood cells, which directly boosts their maximum oxygen uptake (VO2 max). However, this comes at a huge cost to the blood itself. When athletes combine exogenous (e.g. artificially increased/injected) EPO with massive doses of testosterone (which also boosts red blood cells), the blood becomes dangerously thick. It turns from a smooth flowing liquid into a thick, sticky sludge in a condition known as polycythaemia. 

Pumping this thick sludge puts an enormous strain on the heart and the blood vessel walls. Steroids also make blood platelets (the cells responsible for forming clots) stickier and more prone to making larger, tougher clots (Roşca et al., 2021). Add this all together, and the risk of a random blood clot skyrockets.

Stimulants make this even worse by jacking up the heart rate and blood pressure. You are left with thick blood, stiff arteries, sticky platelets, and a heart working in overdrive. It is a recipe for a vessel to burst or a clot to block blood flow to the heart (myocardial infarction, AKA a heart attack) or brain (ischaemic stroke). 

5. Fast Forwarding the Ageing Process

At the core of all these problems is a massive acceleration of the body's natural ageing process. Enhanced athletes are basically trading their long-term health for short-term athletic dominance. 

Processing huge amounts of chemicals and dealing with poor blood flow creates a ton of "free radicals". These are unstable molecules that act like rust in the body. They overwhelm the body's natural defences and roam freely, damaging cells, proteins, and even your DNA. 

If you want to learn more about free radicals, check out this post I wrote. 

This constant damage makes cells age prematurely. Instead of dying off naturally, they turn into "senescent" or zombie cells. They refuse to die and instead sit around pumping out toxic, inflammatory chemicals. For a layman’s-terms explanation of “zombie cells”, see this article from the Mayo Clinic. For a more technical overview of cellular senescence, see this Nature review article by Ajoolabady et al. (2025).

Combined, radicals and senescent cells create a state of constant, low-level inflammation throughout the whole body. It also rapidly shortens telomeres, which are the protective caps on the ends of your DNA. When these caps get too short, cells stop working. Extreme steroid and stimulant use speeds up this shortening, meaning the biological age of the athlete's heart and brain is often older than their actual age.

The Bottom Line

The physiology of PEDs is rather clear, and the Enhanced Games have just displayed the disappointing results of abusing them. The human body is a carefully calibrated system where you cannot drastically change one part without breaking another.

The superhuman results promised by extreme, unregulated drug use come with a massive hidden cost. By stiffening the blood vessels, breaking the brain's natural plumbing, and turning the blood to sludge, these athletes are not just building bigger muscles. They are rewiring and re-plumbing their brains, speeding up their cellular ageing process, and risking severe long-term damage.