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Stimulants & Oxidative Stress

Exploring how stimulants contribute to oxidative stress, its effects on cellular health, and how targeted interventions can mitigate the damage.

January 23, 2025

What is Oxidative Stress, and Why Does it Matter?

Think of your brain as a bustling factory. When everything is running smoothly, the machines (your neurons) work efficiently, producing energy and maintaining essential operations like thinking, learning, and memory. But just like any factory, production creates waste—analogous to the reactive oxygen species (ROS) in your brain. Normally, there’s a cleaning crew (antioxidants) that clears the waste and keeps the factory running without a hitch. However, if the factory speeds up production—due to stress, pollution, or stimulant use—the waste can pile up faster than the crew can handle, causing damage to the equipment. Supporting the cleaning crew with proper nutrition, stress management, and healthy habits helps maintain a clean, efficient factory.

Under normal conditions, the brain tightly regulates dopamine levels to maintain proper neuronal function. The dopamine transporter (DAT) clears dopamine from the synapse and returns it to neurons, where it is either stored for future use or broken down by enzymes like monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Autoreceptors detect high dopamine levels and signal neurons to adjust release. These systems work together to maintain balance and support brain health19.

Stimulants, both prescription and non-prescription, increase dopamine by enhancing its release and blocking its reuptake via DAT, leading to elevated dopamine in the synapse13. Excess dopamine can react with oxygen, producing reactive oxygen species (ROS), which contribute to oxidative stress. While the body has an antioxidant system to neutralize ROS, factors like pollution, UV exposure, smoking, and stimulant use can overwhelm it. The brain is particularly vulnerable to oxidative stress due to its high oxygen demand and polyunsaturated fat content, which may impact cognitive function and memory. 12, 13, 18

How Oxidative Stress Affects the Brain

As mentioned above, oxidative stress occurs when the body has an imbalance between free radicals (reactive oxygen species, or ROS) and antioxidants. This imbalance has been studied for its impact on brain health, including the following areas:

Lipid Peroxidation:

Free radicals can interact with cell membrane lipids, altering their structure and function. These changes affect the stability and permeability of cell membranes, which are critical for proper cell signaling and protection. 11

Protein Oxidation:

Oxidative stress can interfere with proteins, changing their structure and function. In some cases, this may result in the formation of clumps or aggregates, which are associated with aging and challenges in maintaining cellular health.[sup11

DNA Integrity:

ROS can interact with DNA, leading to potential changes or breaks in its structure. This has been associated with disruptions in normal cell function and health.11

Mitochondrial Function:

Mitochondria, often called the energy powerhouses of cells, are particularly vulnerable to oxidative stress. Prolonged exposure to ROS may reduce their efficiency, affecting energy production and contributing to challenges in cellular health and function.11, 30

Model of free-radical formation and its consequences at a cellular level

Best Practices to Support Brain Health and Address Oxidative Stress

1. Stimulant Management

For individuals using stimulants, working with a healthcare professional to manage their use may be beneficial:

  • Proper Dosing: Taking the minimum effective dose, as guided by a healthcare provider, can help promote balanced dopamine levels and maintain optimal brain health. 14, 34
  • Regular Monitoring: Regular medical evaluations can help detect early signs of oxidative stress and adjust treatment as necessary.4, 14.


2. Lifestyle Factors

Incorporating healthy habits helps support the body’s natural defenses against oxidative stress:

  • Healthy Diet: A diet rich in fruits, vegetables, whole grains, and healthy fats provides nutrients that support antioxidant defenses and overall brain health.11
  • Physical Activity: Exercise can boost antioxidant levels and improve mitochondrial function.32
  • Adequate Sleep: Quality sleep is essential for cellular repair and maintaining a healthy balance of oxidative and antioxidant activity.3

3. Antioxidants

The body has natural antioxidant systems, and certain nutrients help support these processes:

  • Endogenous Antioxidants: The body produces enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, which neutralize free radicals.8 
  • Dietary Antioxidants: Consuming foods rich in antioxidants (e.g., vitamins C and E) can help reduce oxidative stress.33

Stasis Contains Powerful Antioxidants to Target Oxidative Stress

Please note that Stasis is a dietary supplement that helps relieve occasional stress. It is not intended to diagnose, treat, cure, or prevent any disease.

Astaxanthin is a powerful carotenoid antioxidant derived from microalgae, recognized for its neuroprotective properties and role in supporting skin health 10, 17.  It has the unique ability to cross both the blood-brain barrier and cellular membranes, enabling it to neutralize free radicals and mitigate oxidative stress in both lipophilic and hydrophilic environments1, 15.  Through its potent antioxidant activity, Astaxanthin has been shown to enhance mitochondrial function, protect cellular structures from UV-induced oxidative damage1, 27. Additionally, it supports brain health by helping to manage oxidative stress and maintain a balanced inflammation response10, 15. 

TetraSOD® is a unique ingredient that supports your body’s natural antioxidant defenses, including enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). SOD is our body’s main defense against oxidative stress and is one of the enzymes in our body belonging to the primary antioxidant system. This system is much more effective than classic antioxidants, such as carotenoids, flavonoids, or vitamins (A, E, C), as it is capable of neutralizing up to 1 million free radicals. Additionally, Tetrasod can aid in recovery after high-intensity workouts like cross-training and endurance.29

Selenium is an essential trace mineral with antioxidant properties, crucial for immune function and thyroid hormone metabolism26 . It contributes to health by supporting the body's natural defenses against harmful compounds and by being incorporated into selenoproteins, such as glutathione peroxidase, which help maintain cellular resilience 22 .Selenium’s involvement in managing oxidative stress and supporting a balanced inflammatory response highlights its importance in overall health. 11,16, 35

Key Study Summaries

The following information is for educational purposes only and is not intended as medical advice. These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease, nor is it intended to promote any specific product.

Oxidative Stress in Prolonged Methamphetamine Use:

A study by Solhi et al. (2014) examined oxidative stress markers in 30 individuals with prolonged methamphetamine use compared to 30 healthy controls. The researchers observed elevated levels of malondialdehyde (MDA), a marker of lipid peroxidation, and lower total antioxidant capacity in methamphetamine users. These findings suggest a potential link between chronic methamphetamine use and oxidative changes in the body.31

Oxidative Stress After Recent Abstinence:

Huang et al. (2013) evaluated oxidative stress in 44 individuals who had ceased methamphetamine use for less than 30 days, compared with 48 healthy controls. The study identified higher levels of oxidative stress markers, such as reactive oxygen species (ROS) and MDA, alongside lower antioxidant enzyme activity in the methamphetamine users. These observations indicate oxidative stress can persist even after recent cessation.14

Antioxidant Levels in Chronic Methamphetamine Users:

Mirecki et al. (2004) analyzed brain tissue from 16 individuals with chronic methamphetamine use and 15 healthy controls, focusing on antioxidant levels. The study found reduced levels of glutathione, a key antioxidant, in the brains of chronic methamphetamine users, reflecting increased vulnerability to oxidative stress.24

Mechanisms of Oxidative Stress in Amphetamine Use:

Yamamoto and Raudensky (2008) reviewed the mechanisms associated with oxidative stress induced by amphetamine-related drugs. The researchers reported that these drugs may increase ROS production, disrupt mitochondrial function, and affect cellular energy reserves. These processes were associated with metabolic changes and inflammation in neuronal systems.36

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