Psychedelic Therapy: Navigating the Neuroplastic Reconfiguration of the Self
Psychedelics as Neuroplastogens – The Neuroscience of the Self
After decades of being considered dangerous, psychedelics have regained attention for their potential to treat mental health disorders such as depression, PTSD, and more. Their ability to induce neuroplastic effects, rewiring the brain’s dysfunctional circuits, has placed them at the forefront of mental health research. As a neuroscientist involved in drug development and personalized medicine, I am closely following how applied science is increasingly harnessing neuroplasticity, the core mechanism behind psychedelics' therapeutic effects.
At the heart of any psychiatric neuroplastogen is its ability to fundamentally alter the very sense of self, often permanently.
Sometimes, this transformation occurs astonishingly quickly. Take war veterans, for instance, where profound changes can be seen after just a single session. Given this tremendous power to affect the very foundation of our self-awareness, the future holds immense promise, offering the potential for groundbreaking treatments, if we balance both the benefits and risks before these therapies are widely implemented.
The Neuroscience of the Self: Dynamic Network Processes
From a neuroscience perspective, the self is not a fixed, immutable entity but rather a dynamic process involving defined functional brain networks. This view of the self as a process, rather than a static "brain area” is key when considering psychedelics, which alter the very circuits that underlie this process.
A key target of psychedelics, and neuroplastic drugs in general, is the Default Mode Network (DMN), which is activated during self-referential thinking, introspection, and the internal narrative that forms our sense of identity. The DMN is intertwined with other brain networks such as the Salience Network, which helps us prioritize important stimuli, and the Executive Network, which governs goal-directed behavior. Together, these networks interact dynamically, contributing to a coherent sense of self in the attractor state space.
In psychedelic therapy, the disruption of these networks is purposeful, as their interaction is assumed to be faulty or 'stuck'. Psychedelics then cause a loosening of synapses that hold the DMN self-referential framework - often leading to a state of complete dissolution of known reality. Upon return, many individuals experience a profound altered sense of identity which is a hallmark of neuroplasticity. This "loosening" underlies a cascade of neurochemical changes, which, in addition to the specific reconfiguration of circuits, are the focus of psychedelic neuroscience.
To rewire the brain, one must first loosen the current Default Mode Network connections.
This reconfiguration is also of great interest in drug development, where key systems such as the serotonergic and dopaminergic pathways are specifically targeted. The long-term functional impact of this disruption on brain connectivity can be tracked through functional connectomics. We now have the tools to understand these processes at both the molecular and functional levels and this field is rapidly advancing.
The Emergence of the New Self: Risks and Uncertainty
As psychedelics rewire DMN, this is akin to the emergence of a metaphorical "new self," ideally one that is less constrained by the rigid, maladaptive neural patterns that underline many mental health disorders.
However, the increased neuroplasticity brought about by psychedelics is not a simple, predictable process. The potential for new neural connections to form carries significant risks. The reconfiguration may not automatically lead to a healthier or more stable self and some individuals experience identity confusion or even detachment from reality even after the effects subside.
The new sense of self is the product of neuroplasticity, psychological history, and the therapeutic process itself, taken together.
While some aspects of this landscape are understood, we still lack data on the risks involved in destabilizing even a dysfunctional self, the processes underlying the new synaptic rewiring, and its persistence; basically, the overall feature space of this inquiry requires broader definition. We have not yet reached an analytical framework to explore these questions systematically, but we are on the right track.
We know that the mandatory therapeutic guidance during the experience plays a key role in shaping the outcome. By guiding individuals through a highly suggestible state, the therapist serves as an anchor to reality at a time when the individual’s perception is highly malleable. However, this power dynamic also carries inherent risks. Recent research has highlighted post-treatment destabilization, adaptation difficulties, and complications in the therapeutic relationship, including a desire to maintain contact beyond treatment. These effects are not unique to psychedelics; they are also observed in conventional psychotherapy, where power dynamics and transference can influence the therapeutic process. Nevertheless, the context can provide serious confounds in, e.g., a clinical trial setting where other drug-related factors need to be discerned.
Because the risks are multifactorial, spanning therapeutic context, physiological factors, and neuroplasticity, the approach to drug safety must also be multifactorial and will require innovative solutions to navigate effectively.
New Directions: A Future of Neuroplastic Network Science
As psychedelics become an established tool in mental health treatment, the long-term effects on brain connectivity and the reconfiguration of the DMN will inevitably become streamlined. Incorporating connectomic biomarkers into both drug development and clinical practice will be essential, as these provide the only cutting-edge and low-cost insights into functional neuroplasticity. Next, collecting metadata on brain network alterations and linking it to patient outcomes will establish a continuous innovation feedback loop, informing the development of additional tailored and effective treatments.
Psychedleic drug development will opens the door to a new science of rewiring the brain, akin to developmental neuroscience.
Just as developmental neuroscience traces how the brain matures and adapts over time, psychedelics provide a unique opportunity to study these transformative processes in the adult brain. The elements of dissolution, emergence, and therapeutic context can be identified and systematically researched, shedding light on how the self is continually redefined by both biological and psychological factors.
Traditional diagnostic systems like the DSM and ICD have long been used to classify mental health conditions, but they fail to capture the complexity of scientific correlates of self-identity and brain function required in the context of psychedelics. We need a new conceptual framework. The Research Domain Criteria (RDoC) framework offers the next best dimensional approach that moves beyond traditional diagnostic categories, considering underlying biological and behavioral constructs and mapping across genes, brain circuits, and behaviors. A similar yet more appropriate multidimensional approach is essential for laying the foundation for the future of psychedelics and for a personalized approach to mental health methods where the sense of self is targeted.
Ultimately, while mistakes are inevitable in the short term, studying the psychedelic-shaped self also opens up exciting possibilities for metacognitive exploration.
The exploration of the psychedelic-shaped self will likely provide insights into the neuroscience of neural networks while also touching on philosophical and psychological dimensions of self-awareness. The lessons learned through psychedelic research could pave the way for deepening new avenues to self-awareness, expanding cognitive flexibility, and fostering personal growth. These insights may ultimately lead to novel approaches to mental health and self-development that extend far beyond the realm of psychedelics themselves.