By

In scientific research, psychedelics have long been linked to changes in mood, behavior, and experience. In recent years, the focus has increasingly shifted from just “serotonin and 5-HT2A” to a broader narrative regarding neuroplasticity: the brain’s ability to adapt, form new connections, and restructure existing patterns. A pathway that frequently recurs in this context is the BDNF-TrkB pathway. That sounds technical, but the underlying idea is easy to explain: it involves signals that help cells grow, connect, and change.

In this article, we outline in a calm, factual manner what BDNF and TrkB are, why this route is interesting in the context of psychedelics, and what can and cannot be concluded from them. In doing so, we make a clear distinction between mechanisms from preclinical research, hypotheses, and what has or has not yet been demonstrated in humans.

What is BDNF and what is TrkB?

BDNF stands for Brain-Derived Neurotrophic Factor. It is a naturally occurring signaling molecule (often called a “growth factor”) that plays a role in the health and adaptability of nerve cells. BDNF is involved in processes such as the strengthening or weakening of synapses (connections between neurons), learning, memory, and recovery after stress. In many popular explanations, BDNF is sometimes presented as the “happiness hormone” for the brain, but that is too simplistic. BDNF is important, but it is one component in a complex network of biology, environment, behavior, and psychological factors.

TrkB (Tropomyosin receptor kinase B) is the receptor that BDNF binds to. You can view BDNF as the “message” and TrkB as the “receiver” that transmits the message within the cell. When BDNF binds to TrkB, it triggers a cascade of intracellular signals associated with, among other things, the growth and adaptation of neural networks. This does not automatically mean “more is better”: timing, location in the brain, context, and individual differences matter greatly.

Why neuroplasticity is such a central concept

Neuroplasticity is an umbrella term for changes in the nervous system, ranging from rapid adjustments in synapse strength to the (temporary) formation of new connections. In the context of mental health, neuroplasticity is often mentioned because rigid patterns in thinking, feeling, and behavior are sometimes difficult to break, especially after prolonged stress or trauma. The idea that the brain can be “more flexible” during certain periods makes it plausible that psychological interventions within such a window can have a greater impact.

It is important to note, however, that plasticity is not synonymous with improvement. Greater plasticity can also mean that someone is more sensitive to environmental influences. Therefore, researchers and therapists often emphasize the importance of context: setting, support, preparation, and integration. Without that context, it is unclear what a change in plasticity means in the long term.

Psychedelics and TrkB: what is the “new insight”?

In addition to the classic focus on serotonin (particularly the 5-HT2A receptor), there is increasing interest in the BDNF-TrkB pathway. In 2023, research appeared that received significant attention because it suggests that certain psychedelics may be able to bind directly to TrkB, the receptor for BDNF. According to this interpretation, psychedelics could enhance the effects of BDNF and thereby support neuroplasticity. This is an intriguing idea, as it would mean that some of the plasticity-promoting effects do not necessarily have to travel exclusively via the known 5-HT2A pathway.

Findings of this type can help explain why psychedelics are linked in research to transient changes in network activity and to a period in which people may be more receptive to new perspectives or behavioral patterns. However, it is essential to emphasize that “potential bonding” and “can support” are not the same as “proven effective as a treatment.” The step from molecular interaction to clinical outcome in humans is large, and there are many unknowns along the way.

What does this mean, and what does it not mean, for depression and other complaints?

In online discussions, the link between BDNF and depressive symptoms is often quickly made. There are indeed studies showing that BDNF levels and TrkB signaling may be involved in stress response and certain forms of depression, but that does not mean that BDNF is a single switch you turn “on” to resolve symptoms. Depression is not a straightforward disorder with a single cause, and moreover, measurements of BDNF (for example, in blood) are not automatically a direct reflection of what is happening in the brain.

The same applies to psychedelics. Even if a psychedelic substance influences TrkB in a certain way, that says little about:

1) for whom this is relevant,

2) with which symptoms,

3) in what dose and context,

4) and with what risks or side effects.

Therefore, it is important to avoid phrases such as “psychedelics cure depression via TrkB.” The human clinical translation is too complex for that, and the scientific substantiation is too incomplete. What you can say, however, is that TrkB provides an additional hypothesis that helps researchers better understand why psychedelics can sometimes accompany long-lasting changes, even after the acute effects have passed.

Decoupling hallucinations and plasticity: why that is relevant

A recurring question in the field is whether the subjective psychedelic experience (such as visual changes, intense emotional material, a sense of “meaning”) is necessary for therapeutic effects. If pathways exist that support plasticity without being fully dependent on 5-HT2A-driven hallucinations, this could eventually be relevant for drug development. Consider agents that might be less intense or more easily dosed in clinical contexts.

At the same time, this subject is also susceptible to oversimplification. Therapy research often emphasizes precisely that meaning-making, emotional processing, and new perspectives can be part of the process. Even if there is a “biological route” that increases plasticity, the question remains what someone subsequently does with that plasticity. The psychological context can therefore still be crucial, even if part of the mechanism turns out to be less dependent on hallucinogenic effects.

What does the research say so far, and where do the uncertainties lie?

The core of the current state of affairs is: there are interesting preclinical and mechanistic indications that psychedelics can influence neuroplasticity, and TrkB is increasingly mentioned in this context as a possible link alongside serotonergic pathways. However, mechanistic plausibility is not yet clinical proof.

Some uncertainties that often remain underexposed in popular summaries:

Translation for people: Much mechanistic work starts in cell models or animal research. That is useful, but cannot be translated one-to-one to human therapy.

Dose and timing: Binding to a receptor does not automatically reveal what functionally happens in the living brain, let alone how long the effects last.

Individual differences: Genetics, previous experiences, stress load, sleep, substance use, and psychiatric vulnerability can all influence outcomes and risks.

Context factors: Expectations, environment, guidance, and integration can help determine whether an experience is supportive or disruptive.

Anyone wishing to delve into the background of BDNF and the surrounding discussion can consult an exploratory forum source, with the caveat that a forum is not peer-reviewed literature. See, for example: https://trip-forum.nl/depressie/langdurige-depressie-en-bdnf/.

Safety and harm reduction: why this is always part of the conversation

When it comes to psychedelics and related substances, safety is not a minor issue. The same factors that make an experience “profound” can also lead to confusion, anxiety, risky behavior, or prolonged dysregulation, particularly in cases of vulnerability to psychosis, bipolar disorder, or insufficient support. Interactions with medications and other substances can also increase risks. Therefore, caution is warranted when making definitive statements, especially online.

Moreover, for substances such as MDMA, sessions can currently only be discussed within scientific research or in clinical practice in a harm-reduction context. In practice, this means focusing information on preparation, setting, risk assessment, and aftercare, without treating it as a regular, freely available treatment.

What practical things can you take away from these kinds of insights?

If you are primarily interested in what these mechanistic insights mean for “real people”, then a sober summary is:

1) The plasticity narrative is becoming broader. 5-HT2A remains important, but possibly not the only input.

2) TrkB is a serious candidate route. Not as a magic solution, but as an extra puzzle piece that can give direction to research.

3) Context remains essential. Even if biology temporarily supports more flexibility, guidance and integration partly determine what someone can do with it.

Anyone considering guided sessions would do well to choose a transparent, harm-reduction-oriented approach, with attention to screening, preparation, and integration. If you would like to read more about how sessions are approached in practice and where you can sign up for an intake, you can do so via https://mdmatherapie.nl/aanmelden-mdma-sessie/. This is not medical advice and no guarantee of an outcome, but a route to ensure you are carefully informed.

Conclusion

The BDNF-TrkB pathway offers an interesting new perspective on how psychedelics might influence neuroplasticity. The idea that substances like LSD and psilocin act not only via classical serotonin pathways but possibly also via TrkB can help better target future studies. At the same time, translating this into clinical effects in humans remains complex and uncertain. Those delving into this subject benefit most from nuance: being curious about mechanisms, critical of claims, and consistent in their attention to safety, context, and guidance.