PSYCHEDELIC THERAPY: What Brains Science Reveals About Altering Substances
- Marcela Emilia Silva do Valle Pereira Ma Emilia
- Oct 21
- 6 min read
🧠 Psychedelic Therapy
The topic of psychedelics is caught between fascination and taboo — but brain science may be rewriting its story.
Today, it returns to the centre of discussions — now scientific — no longer as a symbol of counterculture, but as a legitimate field of modern neuroscience.
From psilocybin to LSD, from MDMA to DMT, substances once viewed with suspicion are now being studied in clinical contexts, with promising results in treating resistant depression, trauma, and anxiety.
But what, in fact, happens in the brain during these experiences?
And why have they sparked such interest among scientists and therapists?
This post does not aim to advocate the use of any substances — quite the opposite.Its goal is to explain the application of neuroscience, in a controlled environment, to understand what happens in the brain when altering substances enter the neural system — with evidence, mechanisms, and boundaries.
🌈 Between Taboo and Revolution
The renaissance of psychedelic research marks a paradigm shift: from prohibition to therapeutic potential.
Science, now freed from stigma, is beginning to uncover how these substances alter perception, emotion, and consciousness — not as an escape from reality, but as an expansion of it.
Early studies from Johns Hopkins University and Imperial College London indicate that, when used in controlled environments, these substances can promote profound reconfigurations in brain connectivity, offering new possibilities for treating complex mental disorders.
More than “mental trips”, it is about understanding how the brain reorganises itself when the boundaries of the self-dissolve.
🔬 The Brain Under Psychedelic Effect
Psychedelics are compounds that alter perception, cognition, and emotion by interacting with brain receptors.
Neuroscience has discovered that some of these psychedelics act primarily on the serotonergic system, binding to 5-HT2A receptors — the same system involved in mood, cognition, and sensory perception.
Clinical definition of psychedelic (FDA, 2024): “Agents that induce expanded states of consciousness with therapeutic potential in resistant disorders.”
Unlike stimulants or sedatives, they increase brain connectivity, dissolving barriers between neural networks and allowing access to memories and emotions previously unreachable.
This increase in brain connectivity arises from the reduction in activity of the default mode network (DMN), responsible for the internal narrative of the “self” and the sense of separation between subject and world.
With the DMN “silenced”, the brain enters a state of hyperconnectivity: regions that normally do not communicate begin to exchange information freely.
It is as if the brain stops following its usual roads and starts exploring new pathways — some chaotic, others deeply revealing.
These new connections explain why many people report sensations of unity, ego dissolution, and expanded consciousness, accompanied by intense emotional meaning.
🧩 Clinical Applications and Recent Findings
Scientific research is beginning to confirm what ancestral cultures have long intuited: under certain conditions, altered states of consciousness can open doors to profound mental reorganisation.
Psilocybin:
Found in certain mushrooms, it has shown effectiveness in cases of treatment-resistant depression, promoting increased connectivity between the medial prefrontal cortex and the hippocampus — regions related to emotional regulation and autobiographical memory.
fMRI studies (Carhart-Harris, Imperial College, 2023) show that this substance increases brain entropy by up to 300% — in other words, it breaks rigid patterns of thought, temporarily disconnecting the DMN (responsible for rumination and the “self”), allowing other regions to communicate freely.
MDMA:
In clinical studies on post-traumatic stress disorder (PTSD), it has proven effective in reducing fear and increasing empathy, through the release of serotonin, dopamine, and oxytocin — allowing the brain to reprocess trauma without emotional collapse.
The amygdala — the fear centre — becomes more accessible, and patients report reliving traumatic memories without the usual weight, enabling the reprocessing of emotions with the prefrontal cortex (regulation).
LSD and DMT:
Broaden sensory perception and dissolve rigid cognitive patterns, creating windows of neuroplasticity that can facilitate emotional learning and creativity.
By stimulating the release of BDNF (brain-derived neurotrophic factor), they promote the growth of new synapses, reconnection of emotional circuits, and reduction of neural rigidity in PTSD and depression.
But there is a crucial point: these substances do not heal on their own.
They merely open a transient brain state of high plasticity — a fertile ground where new connections can emerge, provided they are integrated with appropriate therapeutic support.
Insight only becomes transformation when it finds context and integration.
🌱 Expanded Consciousness and Neuroplasticity
During psychedelic states, the brain enters a phase of hyperplasticity — a moment when old connections loosen and new synapses are formed.
This phenomenon creates the opportunity to reinterpret memories, dissolve repetitive emotional patterns, and restore empathic connections.
Neuroimaging and EEG show that the brain, in these states, displays more integrated and less hierarchical activity, which may explain both the therapeutic effects and the spiritual experiences.
But the most important aspect is not the peak of the experience — it is what comes after. Post-session integration is what consolidates learning.
It is when the brain “decides” which new connections will be maintained and which will fade.
Insight without integration is like a synapse without a neurotransmitter: the message does not cross.
⚖️ Between Risk and Potential
Every expansion requires boundaries.
The use of psychedelics outside a clinical context and without supervision can cause panic reactions, dissociation, and traumatic reactivation.
Neuroscience is still investigating the long-term effects on the serotonergic system and neural structure, especially with repeated use.
Moreover, the use of psychedelics is not recommended for everyone.
It works well when:
There is integrated therapy (pre- and post-session).
The patient has an adequate set and setting.
The disorder is resistant to other approaches.
It is not for everyone:
Risk of psychosis in predisposed individuals.
Drug interactions.
The experience may be too intense without support.
Beyond the biological risks, there are also ethical dilemmas:
To what extent is it legitimate to induce altered mental states to promote healing?
And where is the boundary between therapy and mind manipulation?
That is why science upholds the principle of “set and setting” — mental state and environment — as determinants of the effect.
In other words: it is not only what is consumed, but the emotional and therapeutic context in which the experience occurs.
Neuroscience is still discovering how psychedelics should be used in clinical contexts, and for that reason, their application should be carried out only by trained psychotherapists.
On dosage: microdosing is used, and even this can already produce subtle effects on creativity and mood — although still without robust evidence.
On combination with mindfulness: it has been shown to enhance post-session integration.
On biomarkers: it remains unclear who responds best to these interactions (e.g., high inflammation = better response to MDMA?).
✨ Conclusion – The Future of Psychedelic Neuroscience
Psychedelic therapy represents one of the most fascinating frontiers of modern neuroscience — a point where biology, mind, and meaning intersect.
More than seeking altered states, it is about understanding how the brain can reconfigure itself to heal, learn, and expand.
The challenge now is to balance enthusiasm and evidence, ethics and innovation.
Because perhaps the true potential of psychedelics lies not in the substances themselves — but in the human brain that is finally learning to reorganise itself.
📚 References
Carhart-Harris, R. L., et al. (2014). The entropic brain: A theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience.
Griffiths, R. R., et al. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety. Journal of Psychopharmacology.
Mithoefer, M. C., et al. (2021). MDMA-assisted therapy for severe PTSD. Nature Medicine.
Vollenweider, F. X. & Preller, K. H. (2020). Psychedelic drugs: Neurobiology and potential for treatment of psychiatric disorders. Nature Reviews Neuroscience.
Nutt, D. & Carhart-Harris, R. (2021). The current status of psychedelics in psychiatry. JAMA Psychiatry.
Davis, A. K., et al. (2020). Effects of psilocybin-assisted therapy on major depressive disorder: A randomized clinical trial. JAMA Psychiatry.
MAPS MDMA-PTSD Phase 3 Trial (2023).
FDA Breakthrough Therapy Designations (2024).
APA Guidelines on Psychedelic-Assisted Therapy (2024).
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