Adult neurogenesis is the process by which the adult brain generates new neurons from neural stem cells (NSCs)/progenitor cells. Stem cells are the special type of cell that is able to self-renew (proliferation) as well as convert into other cell types (differentiation) such as neurons:
proliferation
→
differentiation
→
migration
→
maturation
→
functional integration
With respect to cognition, adult-born hippocampal neurons seem to contribute to certain forms of learning and memory (often framed as “pattern separation,” i.e., telling similar experiences apart) and to aspects of stress/mood regulation—at least in animal models.
Is Neurogenesis Possible?
Whether neurogenesis persists robustly across the adult human lifespan has been debated for years, largely because evidence often relies on postmortem tissue and methods that are sensitive to tissue quality and marker choice. Many reviews conclude that some adult human hippocampal neurogenesis likely exists, but its extent and trajectory with aging/disease are still actively investigated.
Research by Spalding et al. (2013) indicates that as many as 700 new neurons are added per day, whilst other work has failed to identify any significant neurogenesis in adulthood. The latest research suggests that adult neurogenesis can take place in two regions of the brain which still maintain pools of Neural Stem Cells: the Dentate Gyrus and Subventricular Zone.
Dentate Gyrus Neurogenesis
The first strong evidence for adult neurogenesis came from a 1998 study by Eriksson and colleagues, where they used a marker called 5-bromo-2-deoxyuridine (BrdU) to identify cell division in hippocampal neurons. This research was considered ground breaking at the time, as it shattered the long-held notion that adult neurogenesis was impossible.
In the proceeding decades, a wider body of evidence has accumulated to suggest that adult neurogenesis does likely take place in a particular region of the hippocampus called the dentate gyrus.
The dentate gyrus is part of the hippocampus that processes information coming from the cortex. It allows the brain to tell similar experiences apart, so that the hippocampus can store distinct memories without “blurring them together”. It can be thought of like a gate, controlling what signals are allowed to pass through for memory retrieval and formation.
The fact there’s evidence to support that this region of the brain can develop new neurons throughout adulthood supports the ability of the brain to learn new things and update memories over a lifetime.
Subventricular Zone Neurogenesis
The subventricular zone (SVZ) is a thin layer of cells that lines the walls of the lateral ventricles in the brain. The new neurons that develop in the SVZ migrate along the rostral migratory stream (RMS) to the olfactory bulb (where the brain processes smell) when they develop into interneurons. It’s been theorised that the SVZ progenitor cells can develop into different cell types and migrate throughout the brain as part of the brains “repair system”.
Neurogenesis and cognition
Even if a compound increases neurogenesis markers (e.g., more dividing progenitors or more immature neurons), cognitive outcomes depend on whether new neurons survive, mature appropriately, and integrate in a way that improves circuit function.
Adult neurogenesis is one form of plasticity among many (synaptic remodelling, myelination changes, dendritic growth), and boosting one metric can be neutral—or even counterproductive—depending on context (stress, sleep, inflammation, disease state).
Neurogenic Nootropics Ranking:
1. Cerebrolysin
Class: Neurogenesis
1/10
Short-term cognitive boost
5/10
Long-term brain enhancement
6/10
Health and Safety Profile
5/10
Quality & strength of evidence
Key Points Summary
- What Cerebrolysin is used for: Most evidence concerns restoring or supporting cognition in impaired brains (stroke/TBI recovery, dementia), not boosting already-healthy cognition.
- Best direct cognitive data are in Alzheimer’s disease: A meta-analysis of double-blind RCTs found small-to-moderate short-term cognitive benefit at ~4 weeks (SMD −0.40, 95% CI −0.66 to −0.13) and better global clinical change (OR 3.32) versus placebo (Gauthier et al. 2015). At ~6 months, cognitive effects were less consistent (SMD −0.37, not statistically significant), though global change remained favorable (OR 4.98) (Gauthier et al. 2015).
- Vascular cognitive impairment/dementia: Reviews report small cognitive improvements in some short-term trials (e.g., MMSE about +0.96 points; ADAS-cog improvement about −2.38) (Cui et al. 2019), and a newer meta-analysis estimates a small effect size in vascular dementia (Cohen’s d 0.35 across 2 RCTs, low certainty) (Masserini et al. 2025).
- Stroke evidence supports “neurorecovery” more than cognition per se: A 2025 meta-analysis found better early neurological recovery (NIHSS change +1.39 points). A reperfusion add-on trial reported lower symptomatic hemorrhagic transformation (OR 0.248) and better day-14 NIHSS, but no day-90 disability difference (Khasanova & Kalinin 2023). This suggests benefit may be early recovery support, which can indirectly help cognitive function during rehab.
- TBI: pooled improvements on broad outcomes, cognitive specifics less clear: Meta-analysis shows a modest improvement on the Glasgow Outcome Scale (mean difference 0.422) with no clear mortality benefit (Jarosz et al. 2023). Cognitive enhancement is plausible in TBI recovery, but endpoints are often global and heterogeneous.
- Prevention/MCI: intriguing but not definitive: A prospective comparative study in high-risk relatives with amnestic MCI reported 0 conversions to dementia over ~2.5 years in treated participants versus an annual conversion rate of 9.5% in controls (Selezneva & Gavrilova 2023). This is hypothesis-generating because the design is not a large blinded RCT.
- Perioperative cognition: mixed signal: In CABG patients, delirium was 0 vs 3 cases, but MoCA scores were lower in the Cerebrolysin group at one follow-up (median 24 vs 27, p = 0.0083) (Stadnik et al. 2025). This cuts against a simple “always cognitive enhancing” narrative.
2. β-Carbolines:
Class: Stimulant & Neurogenesis
2/10
Short-term cognitive boost
4/10
Long-term brain enhancement
4/10
Health and Safety Profile
2/10
Quality & strength of evidence
Key Points Summary
- Monoamine modulation via MAO-A inhibition: Harmine and harmaline are potent MAO-A inhibitors in vitro (reported Kᵢ ~5 nM for harmine and ~48 nM for harmaline), which can raise monoamine tone and plausibly influence motivation/attention indirectly through mood and arousal.
- Human evidence is thin for cognition, stronger for mood/biomarkers: In an RCT in treatment-resistant depression using ayahuasca (β-carbolines + DMT), antidepressant effects were large (day 7 response ~64% vs 27%). This could secondarily improve cognitive function via mood, but it doesn’t isolate β-carbolines as cognitive enhancers.
- A related trial reported higher serum BDNF after dosing (F=4.81, p=0.03; d=0.53), consistent with neuroplasticity signalling—again in a mixed, psychedelic context rather than a clean β-carboline-only test.
- Purified harmine in humans suggests a limited “nootropic window.” A Phase 1 study of oral harmine reported minimal/limited adverse events below about 2.7 mg/kg, while higher doses were associated with vomiting and drowsiness—not a profile that currently supports reliable cognitive boosting in healthy people.
- Preclinical cognition: best evidence is “rescue” of impaired cognition rather than boosting normal cognition: In rodents, harmine/harmaline improved performance in impairment models (e.g., scopolamine, diabetic cognitive dysfunction) alongside reductions in acetylcholinesterase/inflammation markers and improvements in maze measures—suggesting potential for restoration under stress/pathology more than enhancement in healthy brains.
- 9-Me-BC is the dopamine-centric candidate driving most “nootropic” interest (preclinical only): A rat study linked repeated 9-Me-BC treatment to improved spatial learning plus elevated hippocampal dopamine and increased dendritic/spine measures, aligning with a plausible cognition/plasticity mechanism.
- In a toxin Parkinson-like model, follow-up 9-Me-BC dosing was reported to normalize striatal dopamine and partially restore TH+ cell counts (e.g., TH+ counts shifting from ~6,736 ± 238 after toxin to ~7,480 ± 478 with 9-Me-BC follow-up, vs ~7,985–8,199 on the contralateral side). This supports “dopamine-system restoration” signals.
- “Dopaminergic neurogenesis” remains speculative. Increased TH+ cells, dopamine levels, or trophic-factor expression can reflect survival or phenotypic recovery rather than true neuron birth; definitive neurogenesis would require lineage/birth-dating evidence not established by TH counts alone.
- Key limitation for nootropic use: safety and dose sensitivity. MAOI-like interaction risks, nausea/sedation at higher doses, and tremor-related associations for some β-carbolines mean the class carries meaningful liabilities that can negate cognitive benefits.