Brain-Derived Neurotrophic Factor and BDNF Supplements

This article reviews what BDNF does, how it’s linked to cognition and mental health, what happens when BDNF signaling is disrupted, and how lifestyle strategies and selected compounds may influence BDNF levels—based on current scientific literature.

Inside every brain, be it that of a communist revolutionary or a bourgeois swine, there exists a class of proteins called the neurotrophic factors.
These are a group of peptides and small proteins that moderate the birth, survival, function, and death of neurons.

Within this group are the neurotrophins, of which Neural Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) are the most important. Both of these compounds are involved in

NGF is expensive to create in a lab and is therefore significantly under-researched. There are, however, dozens of ways to increase BDNF safely and effectively.

Key roles of BDNF include:

BDNF supports the survival of existing neurons and promotes the growth and differentiation of new neurons and synapses, particularly through activation of its receptor TrkB (tropomyosin receptor kinase B).

BDNF is essential for activity-dependent synaptic plasticity, especially long-term potentiation, the strengthening of synapses that underlie learning and memory. Experimental work shows that learning and memory tasks increase BDNF expression and TrkB activation, and blocking BDNF can impair memory formation.

BDNF is not only crucial for acquiring new memories but also for stabilizing them over time. Animal studies indicate that BDNF signaling is required not only for the initial formation of long-term memory but also for its persistence.

Because of these functions, BDNF is often described as a key molecular mediator of neuroplasticity—the brain’s capacity to change in response to experience.

These new dendrites form tight junctions called synapses with the axon terminals of other neurons. Molecules called neurotransmitters flow through this synapse and allow the two neurons to communicate. This means that the infant and toddler years of the human life cycle are like adorable little five-year plans for the creation of a communicative infrastructure in the human brain.

Altered BDNF levels have been reported in a range of psychiatric and neurological conditions:

Many studies report reduced serum or plasma BDNF in individuals with major depressive disorder compared with healthy controls, with partial normalization after antidepressant treatment. Lower BDNF has also been associated with chronic stress and anxiety states in both animal models and human studies.

Decreased BDNF expression has been observed in brain regions affected by Alzheimer’s disease and other dementias, particularly in the hippocampus and cortex. This reduction may contribute to synaptic loss and cognitive decline.

Altered BDNF signaling has been associated with schizophrenia, bipolar disorder, eating disorders, and obesity. In many of these conditions, lower BDNF levels are correlated with worse clinical status or greater symptom severity, although causality remains unclear.

It’s important to emphasize that BDNF is not a simple “good vs. bad” molecule. Instead, it is part of a complex regulatory network. Low BDNF is often a marker of impaired neuroplasticity, but BDNF increases in specific circuits may also contribute to maladaptive learning (e.g., drug cue reinforcement in addiction models).

Because BDNF enhances plasticity, it is sometimes oversimplified as “the more, the better.” In reality:

BDNF’s actions depend heavily on where and when signaling is increased. For example, boosting BDNF in hippocampal circuits may support antidepressant-like effects and improved learning in preclinical models, while altered BDNF in mesolimbic reward circuits can contribute to drug-seeking behavior in addiction models.

Genetic variants in the BDNF gene (such as the Val66Met polymorphism) can alter how BDNF is produced and released and have been associated with differences in memory, stress response, and susceptibility to psychiatric disorders.

In theory, chronic or excessive BDNF signaling might contribute to aberrant sprouting, seizure susceptibility, or pathological plasticity in some disease states. So far, however, most human data involve modest changes associated with lifestyle, medications, or supplements rather than extreme overexpression.

At present, clinical research is more concerned with restoring impaired BDNF-dependent plasticity than with reducing “excess” BDNF. Real-world interventions (exercise, diet, some drugs, or nutraceuticals) tend to produce physiologic, not extreme, changes.

It means that BDNF is neuroprotective against cognitive decline and can attenuate the effects of the aforementioned mental illnesses.

This pigment that gives ginger and turmeric their yellow color is well known for its potent anti-inflammatory effects, which break the neurological positive-feedback loop of stress, inflammation, and low BDNF. Curcumin's anti-inflammatory effects increase BDNF levels, often above baseline, countering stress-induced reductions. Curcumin must be taken with piperine (black pepper) to improve absorption.

Developed initially to help with stroke and cognitive disorders, Semax is a post-Soviet Union peptide that “rapidly” increases BDNF levels throughout the brain, including the reward system. Because Semax activates the reward system, it should be taken in the morning and not at night, as it may cause insomnia. Interestingly, BDNF’s receptor TrKb is not downregulated (i.e., does not appear less throughout the brain after administration) by Semax but is upregulated, which means that Semax does not form a tolerance. Semax upregulates BDNF/TrkB without apparent tolerance development, meaning that less Semax will be required to achieve the same effects over time. It is a stimulant, anxiolytic, and antidepressant.

The sister compound to Semax, Selank, is another post-Soviet Union peptide that increases BDNF in the hippocampus. Unlike Semax, Selank is primarily an anxiolytic compound with strong anti-depressant effects. Selank’s antidepressant effects have to do with the ability to increase serotonin and dopamine throughout the brain rapidly after administration. This is possibly secondary to its inhibition of the degradation of endogenous opioid peptides. Selank boosts hippocampal BDNF, alongside serotonin, dopamine, and potential opioid modulation.

One of the most rudimentary nootropics, Cerebrolysin promotes BDNF and NGF activity. Cerebrolysin is made of peptides extracted from the brains of pigs. While under-researched in relation to its nootropic effects, Cerebrolysin is an effective treatment for stroke and dementia. Unlike Semax, Selank, and Curcumin, it does not have anxiolytic or antidepressant effects.

Closely related to the racetams group of nootropics, Noopept is another post-Soviet invention. Noopept is metabolized into the chemical cycloprolylglycine, which is an endogenous peptide with strong anxiolytic effects at the GABA receptor, which is the leading site for benzodiazepines and alcohol. Noopept, like Cerebrolysin, increases dendritic proliferation via both BDNF and NGF. Its most potent effect, though, is its short-term cognitive enhancement via AMPA glutamate receptor modulation. Read more about Noopept here and here.

BDNF is central to the brain’s ability to adapt, learn, and recover. It supports neuronal survival, synaptic plasticity, and memory formation, and disruptions in BDNF signaling have been associated with depression, cognitive decline, and other neuropsychiatric conditions.

While low BDNF is often linked to impaired plasticity, the biology is nuanced: context, brain region, and timing matter. Lifestyle interventions such as exercise, adequate sleep, stress management, and a nutrient-rich diet remain the most evidence-backed strategies for supporting healthy BDNF function and overall brain resilience.

Certain compounds—including curcumin, Noopept, Semax, Selank, and others—show promising BDNF-modulating effects in experimental studies and, in some cases, early human trials. However, these should be viewed as adjuncts, not replacements, for foundational behaviors, and their long-term safety and efficacy in broad populations remain under active investigation.

In practice, the most responsible way to “leverage” BDNF is to approach brain health at the systems level: combining evidence-based lifestyle strategies with careful, well-informed use of nootropics or peptides where appropriate, always mindful of individual variability, local regulations, and the evolving state of the science.