What drugs induce neurogenesis? Exploring Pharmacological Triggers of New Brain Cells

October 11, 2025 •

6 min read

Chronic stress and major depressive disorder can significantly decrease neurogenesis in the hippocampus [1]. Emerging research is exploring what drugs induce neurogenesis to potentially counteract this effect and develop new treatments for psychiatric and neurological conditions [2, 3].

Quick Summary

Several classes of drugs are under investigation for their ability to promote neurogenesis, including various antidepressants, mood stabilizers like lithium, and certain psychedelics. The research into these compounds, which act on different signaling pathways, holds promise for developing new therapies for brain health and mental illness.

Key Points

Antidepressants Promote Neurogenesis: Chronic use of SSRIs like fluoxetine and sertraline enhances hippocampal neurogenesis by increasing serotonin and BDNF [7, 8].
Mood Stabilizers Have Neurogenic Effects: Lithium and valproate increase neurogenesis by inhibiting GSK-3β and modulating cell survival pathways [9, 13].
Psychedelics are Psychoplastogens: Compounds like DMT and psilocybin act as 'psychoplastogens' through the 5-HT2A receptor, promoting rapid neural plasticity and neurogenesis [15, 18].
Ketamine Offers Rapid Neurogenesis: This rapid-acting antidepressant works by activating immature neurons and promoting synaptic plasticity through the mTOR pathway [20, 15].
Repurposed Drugs Show Promise: Medications like metformin, traditionally used for diabetes, have shown unexpected neurogenic potential in preclinical studies [21, 22].
Neurogenesis is a Complex Process: These drugs use various pathways, including BDNF, mTOR, and GSK-3β, to promote neurogenesis, demonstrating its complexity [15, 11].
Clinical Translation is Ongoing: Much of the evidence is from preclinical animal models, and further research is needed to confirm the safety and efficacy of inducing neurogenesis in human patients [21, 2].

Understanding Neurogenesis

For a long time, the scientific community believed that the adult brain was incapable of producing new neurons. However, this view has been overturned by discoveries confirming that neurogenesis—the process by which new neurons are generated from neural stem cells—occurs in at least two regions of the adult mammalian brain: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) [4]. This continuous regeneration is vital for brain plasticity, learning, memory, and emotional regulation [5].

Disruptions in neurogenesis are linked to numerous psychiatric and neurodegenerative disorders. Consequently, inducing neurogenesis pharmacologically has become a promising area of research aimed at developing more effective treatments. While no drugs are currently approved specifically for this purpose, a range of existing and experimental compounds have demonstrated neurogenic effects in preclinical studies.

Antidepressants

One of the most well-studied classes of neurogenic drugs is antidepressants. Chronic administration, not short-term use, has been consistently linked to increased neurogenesis in the hippocampus [6]. This effect is considered a potential mechanism explaining the therapeutic lag—the weeks or months it takes for these medications to reach full efficacy.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs such as fluoxetine (Prozac) and sertraline (Zoloft) increase serotonin levels in the brain, which in turn promotes neurogenesis [7, 8]. Studies have shown that SSRIs facilitate progenitor cell proliferation and survival in the dentate gyrus, a key area for hippocampal neurogenesis [7, 8]. The antidepressant effects have been shown to be neurogenesis-dependent in some animal models, further solidifying the link [2]. The action is complex, involving serotonin receptors like 5-HT1A and 5-HT4, as well as downstream signaling pathways that increase neurotrophic factors like brain-derived neurotrophic factor (BDNF) [7, 5].

Other Antidepressant Classes

Beyond SSRIs, other classes of antidepressants have also shown neurogenic potential [6]:

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Drugs like venlafaxine and duloxetine, by increasing levels of both serotonin and norepinephrine, also promote neurogenesis by upregulating neurotrophic factors such as BDNF [5].
Tricyclic Antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs): Older antidepressants like imipramine (TCA) and tranylcypromine (MAOI) have also been shown to increase hippocampal neurogenesis through their effects on various neurotransmitter systems [5, 6].
Atypical Antidepressants: Mirtazapine and bupropion, which act on different receptor systems (including dopamine and norepinephrine), also appear to enhance neurogenesis [5].

Mood Stabilizers

Certain mood-stabilizing medications, primarily used to treat bipolar disorder, also demonstrate neurogenic and neuroprotective effects [3].

Lithium: As a first-line treatment for bipolar disorder, lithium has been shown to enhance hippocampal neurogenesis in animal and human studies [9, 10]. It inhibits glycogen synthase kinase-3 beta (GSK-3β), a protein kinase that negatively regulates neurogenesis, and increases levels of anti-apoptotic proteins like Bcl-2 [11, 9]. Chronic lithium use has been associated with increased gray matter volume in patients with bipolar disorder, possibly related to these neurogenic effects [12].
Valproate: Another prominent mood stabilizer, valproate, has been shown to promote neuronal differentiation in human and rodent stem cell cultures [13]. Its actions include inhibiting GSK-3β and influencing neuronal-glial interactions to enhance neurogenesis [13, 14].

Psychedelics and Ketamine

Recent years have seen a surge in research interest regarding the neuroplastic effects of rapid-acting compounds, including psychedelics and ketamine. These compounds can induce rapid, lasting changes in neuronal plasticity.

Psychedelics

Classic serotonergic psychedelics like psilocybin, LSD, and DMT have been identified as "psychoplastogens" that promote neural plasticity, including neurogenesis [15, 16].

Mechanism: These compounds act on the 5-HT2A serotonin receptor, initiating a cascade of intracellular signals that upregulate plasticity-related genes, including BDNF [15, 17]. The resulting effects include increased dendritic arbor complexity, spinogenesis, and synaptogenesis, with evidence for increased neurogenesis, particularly with DMT [15, 18].
Clinical Implications: These neuroplastic effects are thought to contribute to the rapid, long-lasting therapeutic benefits observed in patients treated with psychedelic-assisted psychotherapy for conditions like treatment-resistant depression and PTSD [16].

Ketamine

Ketamine, a dissociative anesthetic and fast-acting antidepressant, also exerts powerful neuroplastic effects [19].

Mechanism: Unlike SSRIs, ketamine's rapid antidepressant effect is linked to its ability to activate immature, adult-born neurons in the hippocampus, boosting activity in certain circuits [20]. It rapidly increases synaptic plasticity by promoting the synthesis of proteins, including BDNF, and activating the mTOR pathway, leading to increased dendritic spine density [20, 15].
Clinical Efficacy: Ketamine offers rapid symptom relief, but its long-term effects are believed to be mediated by pathways that stimulate neurogenesis and promote sustained brain plasticity [19].

Other Neurogenic Drugs and Research

Several other compounds, originally developed for other medical conditions, are now being investigated for their neurogenic properties.

Metformin: This widely used Type 2 diabetes medication activates a signaling pathway involving AMP-activated protein kinase (AMPK) and cAMP response element binding protein (CBP). This pathway enhances hippocampal neurogenesis and improves spatial memory in mice [21, 22]. Metformin's long history of safety makes it a promising candidate for drug repurposing in neurology [21].
Trametinib: An FDA-approved anticancer drug, trametinib, has been shown to induce neuronal differentiation from neural stem cells in mouse models of Alzheimer's disease by inhibiting MEK1/2 signaling [23]. This was found to restore impaired neurogenesis, rescue neuronal numbers, and recover cognitive function [23].

Comparison of Neurogenic Drug Effects


Drug/Class	Primary Indication	Key Neurogenic Mechanism	Speed of Effect	Animal Model Evidence	Human Clinical Evidence
SSRIs	Depression, Anxiety	Increases serotonin, promotes BDNF synthesis, affects 5-HT1A/4 receptors [7, 5].	Delayed (weeks)	Strong preclinical evidence for increased hippocampal neurogenesis [6].	Neuroimaging suggests increased hippocampal volume, correlating with neurogenesis [5].
Lithium	Bipolar Disorder	Inhibits GSK-3β, increases BDNF and anti-apoptotic proteins like Bcl-2 [11, 9].	Delayed	Robust evidence for promoting neurogenesis in animal models [9].	Linked to increased gray matter and hippocampal volume [12, 10].
Psychedelics	Experimental (TRD, PTSD)	5-HT2A receptor agonist, upregulates BDNF, stimulates synaptogenesis [15, 16].	Rapid (hours-days)	Strong evidence for promoting neural plasticity, including some neurogenesis [15].	Emerging evidence for sustained therapeutic effects, requires more research [16].
Ketamine	Experimental (TRD)	NMDA receptor antagonist, activates mTOR pathway, upregulates BDNF [20, 15].	Rapid (hours)	Confirmed to increase neurogenesis and synaptic plasticity in animal models [20, 15].	Evidence suggests rapid relief, with potential for sustained neurogenic effects [19].
Metformin	Type 2 Diabetes	Activates AMPK, leading to increased neurogenesis and memory improvement [21, 22].	Varied	Demonstrated enhanced neurogenesis and improved spatial memory in mice [21].	Repurposing for neurological conditions is under investigation [21].

Conclusion: The Evolving Landscape of Neurogenic Therapeutics

Our understanding of how drugs can induce neurogenesis is rapidly evolving, moving beyond traditional antidepressants to include rapid-acting agents like ketamine and psychedelics, as well as repurposed drugs like metformin. While preclinical evidence for neurogenic effects is strong across several drug classes, translating these findings into clinical practice and proving causality in humans is challenging. The varied mechanisms—from influencing serotonin and BDNF to targeting GSK-3β and mTOR pathways—highlight the complexity of neurogenesis regulation and offer multiple avenues for therapeutic development. Continued research is needed to better understand the specific mechanisms, define optimal dosing strategies, and confirm the long-term safety and efficacy of these neurogenic effects in humans. The ultimate goal is to leverage these insights to create next-generation neurotherapeutics that can effectively repair and regenerate the brain in response to disease or injury.

Future Research Directions

Biomarker Validation: Developing more reliable biomarkers in humans to assess neurogenesis accurately and correlate it with clinical outcomes. This will involve advanced neuroimaging and potentially blood-based markers [2, 16].
Comparative Studies: Head-to-head comparative studies of different neurogenic compounds to determine which are most effective for specific neurological or psychiatric disorders [16].
Combination Therapies: Investigating synergistic effects of combining neurogenic drugs with non-pharmacological interventions, such as exercise and psychotherapy, to maximize therapeutic benefit [6, 16].
Novel Targets: Continuing to search for new drug targets and screening existing libraries of safe drugs for their neurogenic potential, as was successful with metformin [21].
Genetics and Individualization: Researching genetic factors that may influence individual responses to neurogenic drugs, paving the way for personalized medicine approaches [5].

The therapeutic potential of harnessing neurogenesis is enormous, and the knowledge gained from studying what drugs induce neurogenesis could transform the treatment of mental health and neurodegenerative diseases.

Frequently Asked Questions

No drugs are currently approved specifically for the purpose of inducing neurogenesis. Medications like certain antidepressants or mood stabilizers have demonstrated this effect in research, but they are prescribed for other conditions like depression or bipolar disorder.

For traditional antidepressants like SSRIs, the neurogenic effects typically require chronic, long-term administration, often correlating with the delayed onset of their therapeutic action over weeks or months [6]. Rapid-acting agents like ketamine and psychedelics, however, can induce neuroplastic changes much more quickly [20, 15].

Inducing neurogenesis is not without risks. Some studies suggest that in individuals genetically predisposed to bipolar disorder, increased neurogenesis from antidepressants might contribute to hypomanic episodes [5]. This highlights the need for a personalized approach to treatment and careful patient monitoring.

Yes, several lifestyle factors have been shown to increase neurogenesis in animal studies. These include regular physical exercise, engaging in mentally stimulating activities like learning, and consuming a diet rich in certain polyphenols and omega-3 fatty acids [4, 6].

Antidepressants, particularly chronic SSRI treatment, increase serotonin levels, which influences receptors like 5-HT1A and 5-HT4. This triggers a cascade that increases neurotrophic factors like BDNF, promoting the proliferation and survival of new neurons in the hippocampus [7, 5].

The neurogenic hypothesis of depression suggests that chronic stress can suppress neurogenesis, contributing to depressive symptoms. By increasing neurogenesis, antidepressants may help restore the brain's ability to cope with stress and regulate mood, contributing to long-term remission [2].

Brain-derived neurotrophic factor (BDNF) is a key protein involved in neurogenesis. Many neurogenic drugs, including antidepressants and psychedelics, increase BDNF expression, which enhances the survival and differentiation of new neurons. The BDNF signaling pathway is considered a critical mechanism for the neurogenic effects of these compounds [15, 6].