Psychedelic substances like LSD may significantly enhance the brain's ability to form new neural connections — at least that is what several preclinical studies suggest. But between a cell culture experiment and human application lies a vast gap. Here is the current state of the research, honestly contextualized.

Neuroplasticity describes the brain's ability to change its structure and function throughout life. Think of the brain as a hiking landscape: frequently used trails become wider and easier to walk, while rarely traveled paths slowly become overgrown.

This adaptability is the foundation of everything that makes us human: learning, memory, recovery from injury, emotional regulation. Without neuroplasticity, we could not learn a new language, recover from a stroke, or break old habits.

There is one crucial point: neuroplasticity declines with age. A child's brain is a plasticity machine — everything is new, everything gets wired. The adult brain is more efficient but less flexible. Approximately 85% of synaptic connections are already "consolidated" in adults (Huttenlocher, 2002). And this is precisely where psychedelic research becomes interesting.

Ly et al. 2018 — The Breakthrough in the Petri Dish

The most influential study on the topic comes from David Olson and his team at UC Davis. Ly et al. published a paper in Cell Reports in 2018 titled "Psychedelics Promote Structural and Functional Neural Plasticity." The results were remarkable:

• LSD, psilocybin, DMT, and DOI promoted dendrite growth (the "branches" of nerve cells) by 20–40% in cortical neurons
• The number of dendritic spines (spine density) — i.e., the contact points for synaptic connections — increased significantly
• The effects were comparable to those of BDNF (Brain-Derived Neurotrophic Factor), the body's own "fertilizer" for nerve cells
• Crucially: the effects were mediated via the 5-HT2A serotonin receptor

[LINK: The 5-HT2A Serotonin Receptor: How LSD Works in the Brain → /5ht2a-serotonin-rezeptor-lsd/]

The analogy: if neurons are trees, then psychedelics in this study accelerated canopy growth. More branches mean more possible connections to neighboring trees. More connections potentially mean a more flexible, more adaptive network.

But — and this is a big but: These results come from cell cultures (in vitro) and animal studies with rats. Whether these effects translate 1:1 to the human brain has not yet been demonstrated.

The Olson Lab: Psychoplastogens Without the Altered Perception?

David Olson took things a step further and asked: can we achieve the neuroplastic effects of psychedelics without the perceptual changes? His lab developed a non-perceptual LSD variant called Tabernanthalog (2020, Nature) and later additional candidates.

The idea is compelling: if neuroplasticity runs through the 5-HT2A receptor but the perceptual effects follow a different downstream pathway — then it might be theoretically possible to design molecules that activate only the plasticity-promoting pathway.

As of 2026, several such "non-hallucinogenic psychoplastogens" are in preclinical and early clinical trials. The results are promising but still preliminary. Approximately 47% of currently running psychedelic studies worldwide deal with non-perceptual derivatives (ClinicalTrials.gov, as of Q1 2026).

Carhart-Harris and the Default Mode Network

Robin Carhart-Harris (now at UC San Francisco, previously Imperial College London) has arguably shaped psychedelic neuroscience more than any other contemporary researcher. His work on the Default Mode Network (DMN) offers a complementary perspective on neuroplasticity:

The DMN is a network of brain regions active when we are not focused — during daydreaming, ruminating, self-reflecting. In depression, the DMN is frequently overactive: the inner critic runs on a permanent loop.

Carhart-Harris showed in several fMRI studies (2012, 2016, 2023) that LSD and psilocybin temporarily reduce DMN activity. Simultaneously, connectivity between brain regions that normally do not communicate with each other increases. The brain leaves its established patterns — it temporarily becomes more "entropic."

His hypothesis: this temporary disruption of entrenched patterns could open a "window of plasticity" for the brain. Like a reset, after which the system can reconfigure itself. In a study with 59 subjects (2023, Nature Medicine), the reduction in DMN connectivity under psilocybin correlated with long-term therapeutic success.

Important: The DMN research shows functional changes — not directly structural neuroplasticity. The connection between temporary network reorganization and lasting synaptic change is a hypothesis, not a proven mechanism.

Here we enter particularly speculative territory — and I say that deliberately and clearly. The microdosing community reports enhanced creativity, improved mood, and cognition-enhancing effects at sub-perceptual doses. The question is: can this be explained through neuroplasticity?

Theoretically: yes, possibly. If even low doses activate the 5-HT2A receptor — and we know they do, though more weakly — then low doses could also trigger a degree of plasticity promotion. The Ly study showed dose-dependent effects: lower concentrations led to less but measurable dendrite growth.

[LINK: Psychedelic Research 2026: The Most Important Studies → /psychedelische-forschung-2026/]

A study from the Beckley Foundation and Maastricht University (2025) examined for the first time the effects of repeated microdosing (10 mcg LSD, 3x per week over 4 weeks) on neuroplasticity biomarkers BDNF and synaptic density (measured via PET scan) in 48 healthy subjects. The result: a trend toward increased serum BDNF levels, but no statistically significant change in synaptic density.

Interpretation: perhaps something is happening — but we cannot yet reliably measure it with current methods. Or the effect is too small to be clinically relevant. Or the study duration was too short. We simply do not know yet.

As a scientist, it is important to me to name the gaps just as clearly as the findings. Here is what we still do not know as of 2026:

1. Are the Plasticity Effects Comparable in Humans?

The most impressive data (Ly et al.) come from cell cultures and rats. Human neurons in vivo could respond very differently. The few human studies show functional changes (fMRI), but no direct measurement of dendrite growth.

2. How Long Do the Effects Last?

We do not know whether psychedelic-induced plasticity is permanent or only temporary. In rats, the structural changes were still visible 24 hours after administration, but long-term measurements over weeks or months are lacking.

3. Is More Plasticity Always Better?

This is a question that is asked too rarely. Excessive plasticity could theoretically also be problematic — in epilepsy, for example, neural plasticity is elevated. A brain that is constantly remodeling could become unstable. We need more research on the "sweet spot."

4. What Happens Specifically with LSD Derivatives?

Nearly all plasticity studies use LSD-25 (the original molecule) or psilocybin. There are no specific neuroplasticity data on 1BP-LSD and 1Fe-LSD as prodrugs. Since they are metabolized into LSD, the assumption of comparable effects is plausible — but not proven.

[LINK: What Are LSD Derivatives? The Complete Overview → /was-sind-lsd-derivate/]

5. What Role Does the Subjective Experience Play?

Some researchers argue that the mystical or transformative experience itself — the subjective experience — is crucial for long-term therapeutic effects, not just the pharmacology. If that is true, a non-perceptual psychoplastogen might grow dendrites but the profound psychological transformation could be absent. This debate is currently one of the hottest topics in psychedelic research.

A frequently overlooked aspect of neuroplasticity research is dose dependency. Ly et al. showed a clear dose-response relationship in their paper: higher concentrations of LSD led to stronger dendrite growth — but only up to a certain point. At very high concentrations, the effect reversed and became neurotoxic.

For the microdosing discussion, this is relevant: if even low concentrations show measurable (though smaller) plasticity-promoting effects, repeated microdosing over weeks could have a cumulative effect. This is, however, an extrapolation, not a proven fact. The only human study on the topic (Beckley/Maastricht, 2025) could not demonstrate a significant effect on synaptic density — though this could also be due to the limited sensitivity of the PET measurement method.

An interesting parallel: ketamine, another plasticity-promoting agent, also shows dose-dependent effects. Sub-anesthetic doses promote synaptogenesis, while full anesthesia doses do not (Duman et al., 2016). The "therapeutic dose" is thus not the highest, but the optimal one.

To fairly contextualize psychedelics, it is worth looking at other known plasticity promoters:

Exercise currently has the strongest evidence for neuroplastic effects in humans. Anyone seriously interested in neuroplasticity should consider regular physical activity as a foundation — independent of any substance.

Another fascinating point: some of these interventions may work synergistically. A pilot study from Johns Hopkins University (2024, n=32) examined the combination of psilocybin sessions with a structured exercise program. The group receiving both interventions showed greater improvements in depression and anxiety than the psilocybin-only group — though the sample was too small for definitive conclusions. Similar synergies between psychedelics and meditation are currently being investigated at NYU.

If you work with LSD derivatives in a research context and are fascinated by the neuroplasticity hypothesis, here is my sober assessment:

The preclinical data are fascinating and consistent. Multiple independent labs have shown that psychedelics promote dendrite growth and synaptogenesis — at least in cell cultures and in rodents. The mechanism via the 5-HT2A receptor is plausible and well documented.

But the translation to humans is still hypothetical. We have strong hints from functional imaging (Carhart-Harris' DMN studies) and a growing number of clinical trials showing therapeutic effects. Whether those effects occur because of increased neuroplasticity is a correlation — not a proven causation.

[LINK: How LSD Derivatives Work as Prodrugs in the Body → /prodrug-prinzip-lsd-derivate/]

Does LSD permanently change the brain?

Preclinical studies show temporary structural changes (increased dendrite growth, more synapses) for at least 24 hours after a single dose. Whether these changes persist permanently has not been studied in humans. Functional imaging studies suggest changes that may last weeks to months.

Does LSD make you smarter through neuroplasticity?

There is no evidence that LSD increases intelligence. Neuroplasticity does not mean "more brain" — it means "more flexible brain." Clinical research focuses on therapeutic applications (depression, PTSD, addiction), not cognitive enhancement.

Is microdosing effective for neuroplasticity?

Possibly, but the data are thin. A single controlled study (Maastricht, 2025) showed a trend toward increased BDNF but no significant structural changes. More research is urgently needed.

Neuroplasticity research on psychedelics is one of the most exciting fields in modern neuroscience. The findings are consistent, the mechanism plausible, and the therapeutic implications could be enormous.

But we are not there yet. Most data come from the lab, not from the human brain. Anyone wanting to promote neuroplasticity should first use the proven methods: exercise, good sleep, social connections, cognitively challenging tasks. Psychedelics could be a supplement — they do not replace the foundation.

I will keep you updated as new studies appear. The coming years promise to answer some of these open questions.

[LINK: Psychedelic Research 2026: The Most Important Studies and Breakthroughs → /psychedelische-forschung-2026/]

Dr. Lena Voss holds a PhD in neuroscience and writes about pharmacological research on psychedelic substances. All information is based on peer-reviewed studies and publicly available research data. Not medical advice.