Neurotransmitters as Software: How Living Hardware Rewrites Itself

Neurotransmitters as Software: How the brain rewires Itself

The human brain is often compared to a computer, but the analogy usually falls short. A silicon processor is rigid and unchanging, whereas the brain is living hardware. Its circuitry is plastic—constantly reshaping itself in response to internal neurochemistry and external experience. Neurons grow, prune, and strengthen their connections over time. This means the brain is not a fixed machine but a biological system that rewrites its own operating structure as it runs (Kolb and Gibb, 2011; Pascual-Leone et al., 2005).

If the brain is living hardware, then neurotransmitters are its software. They provide the chemical instructions that determine how neurons communicate and how networks adapt. Dopamine codes for reward and motivation, serotonin for mood and resilience, glutamate for learning, GABA for calm, and acetylcholine for attention (Purves et al., 2018). These signals act like lines of code that run continuously in the background. But unlike digital software, neurotransmitter code doesn’t just execute—it also rewrites the very hardware it runs on.

 

Software That Rewrites Hardware

When neurotransmitter activity repeats, it leaves a structural mark on the brain. This is why habits, moods, and even personality traits emerge from neurochemistry: repeated firing of certain pathways strengthens them, while unused connections gradually weaken and dissipate (Hebb, 1949; Draganski et al., 2004).

Stress provides a clear example. Chronic cortisol elevation weakens the hippocampus, disrupts memory, interferes with prefrontal cortex and executive function, and suppresses serotonin production (McEwen, 2007; Lupien et al., 2009; Chaouloff, 2000). Low serotonin in turn makes the brain more vulnerable to stress, which fuels even higher cortisol. This often creates a downward spiral where the individual will eventually burn out or experience a nervous breakdown (McEwen, 2007). A rest period is usually needed to bring down cortisol levels, increase serotonin production, and reboot the system.

An upward spiral is also possible. If cortisol is reduced and serotonin balance restored, resilience improves. Stress hormones no longer spike as high, which protects serotonin production and receptor sensitivity, further stabilizing mood. Over time this creates an upward spiral: balanced chemistry strengthens the hardware, and stronger hardware supports healthier neurotransmitter production and regulation (Lupien et al., 2009; Arnsten, 2009).

 

 

Addiction: Unsustainable Software and Hardware Rollback

Addictive compounds—like nicotine, caffeine, or kratom—offer short-term benefits by strongly activating receptors. But with repeated use, the brain adapts defensively by downregulating or altering those receptors, reducing sensitivity to maintain balance (Xiao et al., 2019). This is the brain’s way of throttling its own hardware when the software is overstimulating it.

The problem comes during withdrawal. Once the compound is removed, receptor sensitivity remains altered, leaving the brain below baseline function. PET and SPECT studies show that smokers in early abstinence have abnormal nicotinic receptor availability compared with non-smokers (Brody et al., 2014). This contributes to blunted dopamine release, weak serotonin regulation, and heightened stress reactivity (Volkow et al., 2011).

In this depleted state, the brain is highly vulnerable to relapse. Two forces drive this:

Bias toward stronger circuits:

High cortisol and low serotonin bias the brain toward its most reinforced pathways. These are often negative behavioural patterns that offer some form of cheap dopamine release to combat stress (Arnsten, 2009; McEwen, 2007).

State-dependent activation:

Stress states act like passwords, reactivating old memories and habits that were encoded under similar neurochemical conditions. Withdrawal itself re-activates and reinforces the very circuits the person was trying to escape (Bouton, 2004; Koob and Le Moal, 2008).

Withdrawal, therefore, doesn’t just weaken the system—it actively invites old reactive habits back in.

 

Botanicals as Sustainable Patches

Not all compounds act this way. Some interventions behave more like clean software patches—they optimize function without forcing extreme adaptations. 

Kanna (Sceletium tortuosum)

Kanna occupies a unique position among psychoactive botanicals because it does not merely stimulate neurotransmitter release—it alters how emotional and cognitive circuits respond to stress at a systems level. Neuroimaging and clinical studies show that standardized Sceletium extracts significantly reduce amygdala reactivity to perceived threat while preserving prefrontal cortex function (Terburg et al., 2013). In software terms, kanna dampens runaway fear and stress subroutines while keeping higher-order executive processes online.

Its primary alkaloids—mesembrine, mesembrenone, and Δ7-mesembrenone—act through a multi-target mechanism. Mesembrine inhibits serotonin reuptake (SERT) and modulates vesicular monoamine transporters (VMAT), increasing the availability of serotonin, dopamine, and other monoamines without forcing excessive synaptic release (Coetzee, López and Smith, 2016). Mesembrenone, in contrast, acts as a potent PDE4 inhibitor and exhibits cannabinoid receptor affinity, contributing to anxiolytic, anti-inflammatory, and neuroprotective effects (Terburg et al., 2013).

Crucially, PDE4 inhibition increases intracellular cAMP signaling, a pathway strongly associated with neuroplasticity and neurogenesis. Through this mechanism, Sceletium does not simply alter mood states—it enhances the brain’s capacity to reorganize itself (Terburg et al., 2013).

Unlike addictive stimulants that provoke receptor downregulation and hardware rollback, kanna functions as a stabilizing patch. It lowers stress-driven cortisol signaling, preserves serotonin sensitivity, and biases learning toward calm, adaptive patterns rather than reactive ones (Swart and Smith, 2016).

Bacopa monnieri

Bacopa supports serotonin, dopamine, and acetylcholine signaling while lowering cortisol (Benson et al., 2013). Randomized controlled trials show that it improves memory, reduces anxiety, lowers morning cortisol, increases cerebral blood flow, and raises BDNF—an essential growth factor promoting neuroplasticity (Goswami et al., 2021). In metaphorical terms, bacopa is a memory-optimization patch that shields serotonin production from stress-driven suppression.

 

Lion’s Mane (Hericium erinaceus)

Lion’s Mane supports cognition, learning, and emotional balance by stimulating nerve growth factor (NGF), a key driver of brain repair and plasticity. Its hericenones and erinacines promote neurogenesis and synaptogenesis, improving memory, focus, reaction time, and learning capacity (Mori et al., 2009; Phan et al., 2014). Its beta-glucans further protect neural tissue through antioxidant and anti-inflammatory effects.

Why Sustainable Patches Matter

These compounds differ from addictive stimulants in a crucial way: they do not drive receptor burnout, downregulation, or loss of sensitivity. The hardware is not left weakened when use stops. Instead, they gently rebalance neurotransmitters and support long-term resilience (McEwen, 2007).

Trying to use physically addictive compounds as patches creates unstable loops—driving adaptation during use and rollback during withdrawal. Stress and imbalance bias the system toward old destructive code. But sustainable compounds, lifestyle practices, and supportive environments can act as stable patches, installing new programs that guide the hardware toward balance and resilience.

By choosing inputs that sustain rather than exhaust the system, we can guide the brain into upward spirals of clarity, adaptability, and strength. What begins as a small tweak in chemistry can, over time, transform the living hardware itself—altering habits, behaviour, and even personality.

Chronic Cortisol Elevation: When Stress Rewrites the Hardware/ "Downward Spirals"

Chronic elevation of cortisol is one of the most powerful forces capable of reshaping the brain’s hardware. While acute cortisol release is adaptive and enhances short-term survival, prolonged exposure produces structural, functional, and neurochemical changes that bias the system toward stress-reactive states rather than reflective, goal-directed processing (McEwen, 2007).It could be taken further to argue that chronic stress erodes inhibition and self-control—the very executive functions that most clearly distinguish the human brain from that of lower primates.

Hippocampus:
Sustained cortisol exposure impairs memory formation, suppresses adult neurogenesis, and causes dendritic atrophy in hippocampal neurons. Over time, this weakens learning capacity, contextual memory, and the brain’s ability to regulate stress responses effectively (McEwen, 2007; Lupien et al., 2009).

Prefrontal cortex:
Chronic stress reduces synaptic connectivity and dendritic complexity in the prefrontal cortex, the region responsible for executive control, planning, emotional regulation, and impulse inhibition. As prefrontal function declines, top-down regulation over emotional and limbic circuits weakens (Arnsten, 2009; McEwen and Morrison, 2013).

Amygdala:                                                                                                                                               In contrast to the hippocampus and prefrontal cortex, chronic cortisol exposure strengthens the amygdala. Stress increases dendritic arborization, synaptic density, and excitability within amygdala circuits, heightening threat detection and emotional reactivity (Vyas et al., 2002; McEwen, 2007). As a result, neutral or ambiguous stimuli are more readily interpreted as threatening, biasing perception toward anxiety, irritability, and negative emotional tone.

At the same time, weakened prefrontal control reduces inhibitory regulation of the amygdala, allowing limbic signals to dominate behaviour. This shift promotes impulsivity, emotional volatility, and stress-driven decision-making at the expense of reflective reasoning (Arnsten, 2009).

Executive function:
As prefrontal networks degrade and amygdala influence increases, executive function declines. Attention, working memory, emotional regulation, impulse control, and decision-making all become compromised, particularly under stress (Arnsten, 2009).

Neurochemistry:
Elevated cortisol suppresses serotonin synthesis and disrupts dopaminergic signaling, while increasing both adrenaline production and adrenergic sensitivity. This neurochemical imbalance reduces mood stability, motivation, and reward sensitivity, while simultaneously increasing vulnerability to anxiety and depressive states (Chaouloff, 2000; Volkow et al., 2011).

Network balance:At the systems level, chronic stress shifts neural activity away from reflective, goal-directed prefrontal networks toward amygdala-dominant threat-processing circuits. This transition reinforces fear conditioning, emotional reactivity, and habitual stress responses while reducing cognitive flexibility and resilience (McEwen, 2007; Arnsten, 2009).

Chronic cortisol does not merely alter mood—it actively rewires the brain toward survival-oriented, threat-focused operating modes. Left unchecked, this process entrenches downward spirals of anxiety, impaired cognition, and emotional dysregulation, making recovery increasingly difficult without interventions that reduce stress signalling and restore neurochemical balance.

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