Exercise as a Nootropic: Neurological Mechanisms of Cognitive Enhancement

Regular, moderate-pace running physically increases the hippocampal volume, the region of the brain associated with memory consolidation and recall. This is one of the many benefits that exercise brings with it.

The physical benefits of exercise are justifiably represented in our modern culture. But a long series of studies shows that aerobic training and resistance training may bring the nootropic benefits we seek from stimulants, exotic herbs, and nutritional supplements.

What are nootropics?

This term was coined by Corneliu Giurgea in 1972, who set up the criteria for a substance to be a nootropic as "any agent that measurably enhances cognitive performance: memory, focus, processing speed, or neuroplasticity in a healthy brain through a defined biological mechanism.”

By this definition, caffeine is a true nootropic, and its acute effects are well studied. It enhances focus, increases memory recall, and promotes wakefulness.
Caffeine comes under the stimulant class of nootropics; its main benefits are acute. The long-term nootropic effects are marginal and do not have a strong correlation.

Can nootropics increase intelligence?

Nootropics, by definition, increase cognition temporarily or can increase baselines over time.

Intelligence is highly genetic, around 80% in adults. Nootropics cannot change this genetic ceiling but can help one reach it.

There are some stricter nootropics, such as Semax and Bacopa monnieri, which truly make a difference in intelligence. Semax makes the brain release BDNF, which is essentially the Miracle-Gro of the brain. It encourages growth, survival, and plasticity of neurons. Bacopa increases dendritic length and branching, which physically increases sites for synaptic connection, which is the neurological basis of memory encoding. DHA, an omega 3 fatty acid, is a key structural component of myelin. It improves the compaction and fluidity of the sheath, reducing charge leakage between nodes and enhancing signal fidelity—making transmission faster and more reliable.

What is Intelligence?

Intelligence in a biological sense can be quantified into neurological components such as neuroplasticity—the brain's ability to form new connections—neuron survival, REM sleep efficiency, memory consolidation, memory recall, and neural as well as synaptic genesis.

Further, general motivation to get any task done and maintaining focus can also come under the domain of general intelligence/learning.

The Biological Basis of Motivation

Motivation is primarily controlled by neurotransmitters called dopamine and norepinephrine.

Dopamine:

It drives us to chase pleasure. It does not fire during pleasure but in anticipation of pleasure. Motivation is controlled biologically by dopamine production in the brain, its uptake in the brain, dopamine receptor sensitivity, and receptor density. A popular example of dopamine downregulation is doom-scrolling. It artificially stimulates the feeling of anticipation for the next reward, which comes easily with a single scroll. This causes a massive spike in dopamine. Repeated spikes cause neurons to downregulate dopamine receptors (i.e., to withdraw receptors) to protect themselves, which decreases motivation to do other things

Norepinephrine:

Norepinephrine is the second basis of the motivation response. While dopamine gives value to a task and can make you “want” to do it, norepinephrine acts more acutely. It acts in the present moment to amplify the response to something you are paying attention to. It amplifies the signal and gives present urgency to act on it. A healthy dopamine response can make you sit for a task, but without an appropriate norepinephrine response, the stimuli in front of you have no weight, and it feels bland. The want to do it is there, but there is no readiness or urgency signal to actually carry out the task in the moment.

The Biological Basis of Focus

Focus is regulated by an antagonistic pair of neurotransmitters—glutamate and GABA—which act as accelerators and brakes for neuron firing, respectively. Particularly, dopamine rises in the prefrontal cortex when we anticipate reward from any task. Dopamine primes the neurons for the task, then glutamate fires neurons, which actually leads to encoding and data transmission. While GABA silences all other background inputs, so we can actually differentiate signal from noise. These are the executors for any focus-related task, but the main drivers, which actually give signals on what to focus on and what to filter out, are acetylcholine and norepinephrine.

Acetylcholine: It is released from the region of the brain known as the basal forebrain. It suppresses irrelevant activity in the cerebral cortex. It sharpens the signal-to-noise ratio across regions of the cortex. This is different, as glutamate and GABA act on a particular synapse only. It is the neurotransmitter that controls the quality of attention: how precisely you can lock in a task and filter out every other stimulus. Low acetylcholine activity is associated with mental fogginess and difficulty sustaining a train of thought despite motivation being there.

Norephinephrine: It is produced in the region of the brain known as the locus coeruleus. It is responsible for alertness and arousal. It amplifies all the stimuli being received. If acetylcholine controls the precision of cortical response, then norepinephrine controls the intensity of the response. It essentially increases the intensity of all the signals while acetylcholine filters it out.

Now stimulating nootropics such as caffeine work by increasing dopamine uptake in the brain indirectly by blocking adenosine receptors, while calming nootropics work by increasing GABA, which blocks the surrounding sound and helps you focus.

The Biological Basis of Intelligence

Intelligence is governed by the physical architecture of the brain. While the chemical imbalance only facilitates the signals between the various parts of the brain, the underlying architecture is what controls the efficiency and quality of the response.

Neuroplasticity: It refers to the brain’s ability to form new connections and prune out old ones in response to learning signals received. Higher neuroplasticity means that the brain can encode new information rapidly and connect it with existing knowledge structure by reorganizing. It is what facilitates acute learning—the strengthening of existing connection as a response to learning. This is known as long term potentiation. Without it, you don't actually learn anything despite paying attention. It also controls long-term learning through practice.

Neuron genesis: Neurogenesis is the birth of new neurons. In adults, it only takes place in the dentate gyrus of the hippocampus. The new neurons are efficient in LTP (short-term memory formation) and are the best choice out of the existing neurons in the hippocampus for memory consolidation. The old neurons had stored memories before and hence have a bias towards the old memories. If neurogenesis is inefficient. Old neurons are used for consolidation, which causes memories to merge, and hence neurogenesis is essential for learning and memory differentiation.

Synaptic genesis: Synapses are the physical sites of memories. Any memory is stored via a pattern of synapses. While LTP creates weak links between existing neurons for temporary memory storage, the physical synapse creation makes the memory long-term. Hence, synaptic genesis is directly responsible for long term memory encoding.

Myelination: Axons are the long projections of the neurons that transmit signals to the synapses. Myelination is the insulation of axons by a fatty sheath called myelin. Rather than traveling the full length of an axon, myelinated signals jump between deliberate gaps in the sheath—making transmission up to 100 times faster than unmyelinated fibers. A thicker, more compact myelin sheathing enhances the speed and fidelity of the signal transmission. This translates to higher raw processing, learning, and cognition speeds.

BDNF: The Brain’s Growth Signal

Lactate is released from muscles during sustained moderate- to high-intensity exercise. While a hormone called irisin is also released from contracting muscles into the bloodstream. Both of these cross the blood-brain barrier, where the lactate binds the HCAR1 receptors while the irisin binds integrin receptors, both of which activate the CREB pathway, which triggers the release of BDNF.

BDNF’s major role is in neurogenesis. Consistent running has shown an increase in volume of the hippocampus, the region of the brain where neurogenesis primarily takes place, which is also responsible for memory consolidation. This indicates that aerobic exercise has a strong correlation with increased memory recall and consolidation.
BDNF also strengthens the prefrontal cortex, which is the region responsible for focus and sustained attention. An elevated BDNF baseline corroborates an increased attention span and clear focus.

Chronic elevated cortisol is neurotoxic. BDNF buffers the hippocampus from the cortisol-induced shrinkage. Further, a higher BDNF baseline corresponds to more constructive sleep.

Effect of Aerobic Exercises:
Studies show that consistent moderate-pace running increases BDNF baseline in the brain. BDNF does not create tolerance, so the effects are prolonged. However, it is seen that vigorous exercise such as HIIT results in an acute spike in BDNF greater than a moderate running session. The BDNF spike is found to last from 30 to 60 minutes, with its downstream effect remaining much longer in the system. This creates ideal timing for cognitively demanding sessions.

Elevated BDNF levels drive neurogenesis in the hippocampus, which is observed to increase the hippocampal volume by 3.4% in adults.

Beyond BDNF, aerobic activity leads to an acute spike in dopamine and norepinephrine, which creates a window of heightened motivation and cortical arousal, respectively. Further, over a period of increased aerobic activity, dopamine receptor (D2) density increases, which makes the brain more sensitive to the neurotransmitter, hence greater general motivation. It also increases dopamine and norepinephrine baselines over weeks.

The increased BDNF levels also promote the cholinergic neurons (which are responsible for acetylcholine synthesis) to upregulate choline acetyltransferase, which synthesises acetylcholine from choline.
Further, aerobic activity increases blood flow, which improves delivery of raw material such as choline and omega-3 fatty acids to the brain.

In the background, aerobic exercise also boosts GABAergic tones, which reduces noise and promotes excitation-inhibition balance.

Effect of Resistance Training:

Resistance training does not induce an acute spike of BDNF as found in aerobic activity. But it has a signature spike in IGF-1 hormones—insulin-like growth factor. Heavy compounds lift and trigger the pituitary gland to release growth hormone, which then results in the release of IGF-1 in the liver. It triggers BDNF release through a parallel pathway. It itself independently supports neurogenesis. However, the main nootropic effect of IGF-1 lies in its support of synaptic plasticity. IGF-1 increases the density and strength of synaptic connections, which are the physical basis for memory encoding and learning. It also promotes neuron survival by suppressing the pathway for neuron death. It also supports myelination, which is the insulation of neural connections, which makes the nerve signals faster.

IGF-1 promotes structural neuroplasticity by increasing the number of synapses and supporting their survival. BDNF makes the existing connections stronger and the transmission through them more efficient by making the synaptic receptors more sensitive to signals (memory encoding) and strengthening the existing synapses and regulating the firing of neurons while learning (via glutamate).

Heavy compound lifts trigger an acute testosterone spike, which upregulates dopamine synthesis and receptor (D2) density. Here the testosterone interacts with dopamine in such a way that the afterglow after lifting is much more motivation-centered than pleasure-centered, as observed in running.

It strongly triggers norepinephrine response, resulting in the neurotransmitter’s acute spike.

The perhaps most important benefit of exercise, whether it be running or lifting, is the decrease in chronically elevated levels of cortisol. Elevated levels of cortisol damages every beneficial mechanism we have discussed. It reduces the hippocampal volume. It directly promotes neuron death. It is destructive to sleep and hence to memory consolidation. It also downregulates the dopamine and norepinephrine sensitivity. It disrupts acetylcholine signaling. Degrades myelin integrity over time. Inhibits LTP.

By the definition of Giurgea, exercise is a nootropic. It measurably enhances memory, processing speed, cognition, and neuroplasticity through defined biological mechanisms. Caffeine’s effects are acute, while Semax and Bacopa require constant dosing with side effects.

Exercise brings the same structural changes naturally and compounds them. BDNF baselines increase, motivation and alertness increase, memory consolidation improves, and cortisol is kept in check, which protects everything.

It increases intelligence and has no withdrawal or side effects.