Exploring Psychedelic-Assisted Therapy for Functional Seizures

Overview: Functional seizures, also known as dissociative seizures or psychogenic non-epileptic seizures, are disruptions in normal functioning caused by psychological factors rather than abnormal brain activity. Current treatments, primarily psychological therapies, often lack effectiveness. A recent paper explores the potential of psychedelic-assisted therapy for treating functional seizures. Psychedelics like LSD, psilocybin, and ketamine show promise in improving brain connectivity and reducing symptoms. Initial case studies and surveys suggest benefits, but more rigorous research is needed. Utilizing complexity science to understand brain dynamics could enhance the effectiveness of psychedelic-assisted therapy, offering new treatment possibilities for functional seizures.

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Understanding Functional Seizures: Challenges and Treatment Options

Functional seizures, also known as dissociative seizures, non-epileptic attack disorder, or psychogenic non-epileptic seizures, are a common presentation of functional neurological disorder.

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These seizures are characterized by episodic disturbances of normal functioning and reduced self-control. Unlike epileptic seizures, functional seizures are not caused by abnormal electrical activity in the brain. Instead, they stem from psychological factors, making them complex and challenging to diagnose and treat effectively.

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Functional seizures have a significant prevalence, with estimated rates ranging from 3.1 to 23.8 per 100,000 people per year. Despite their prevalence, there is no standardized care pathway for managing functional seizures. Misdiagnosis, delayed diagnosis, and the prescription of improper medications, such as antiseizure medications, can exacerbate symptoms and lead to worsening conditions. This highlights the urgent need for more accurate diagnostic methods and effective treatment options.

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Currently, psychological therapies are considered the first-line treatment for functional seizures. However, these therapies have limited supportive evidence of efficacy, leaving many patients without adequate relief. One of the critical challenges in treating functional seizures is the lack of understanding of the underlying brain mechanisms involved.

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The recent paper titled “Exploring Psychedelic-Assisted Therapy in the Treatment of Functional Seizures: A Review of Underlying Mechanisms and Associated Brain Networks” aims to address this gap. By reviewing the potential mechanisms and brain networks associated with functional seizures, the paper explores the innovative approach of psychedelic-assisted therapy as a possible treatment option.

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Psychedelic-Assisted Therapy: A Novel Intervention for Functional Seizures

A novel intervention with potential relevance for treating functional seizures  is psychedelic-assisted therapy, which involves psychotherapy augmented by the use of psychedelic drugs such as LSD, psilocybin, DMT, ayahuasca, mescaline, ketamine, and more. This approach is gaining interest due to its potential therapeutic effects on conditions closely related to functional neurological disorder, such as depression, anxiety, and PTSD.

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A small but growing number of studies, patient surveys, and reviews have explored the role of psychedelics as a treatment for functional neurological disorder. These investigations are motivated by several factors:

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1. The close relationship between functional neurological disorder and mental health conditions.
2. The high incidence of patient-reported psychedelic self-treatment for these disorders.
3. Mechanistically based arguments suggesting a match between psychedelic therapeutic effects and functional neurological disorder pathophysiology.

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Two recent case reports signal promise for this innovative approach. In one case, a patient with functional neurological disorder characterized by sensory and motor paralysis of the left arm was successfully treated with intranasal esketamine. Esketamine, a form of ketamine administered via nasal spray, has been approved for treatment-resistant depression and has shown rapid antidepressant effects, making it a promising candidate for treating other complex neurological conditions.

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In another case, a patient experienced significant reductions in the severity and frequency of functional seizures, along with marked improvements in depressive symptoms and overall well-being, following sublingual and intranasal ketamine-assisted therapy (KAT). This therapy involves the administration of ketamine in conjunction with psychotherapy, leveraging ketamine’s rapid-acting antidepressant properties to enhance therapeutic outcomes.

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Additionally, a recent survey of patients with functional neurological disorder found that 15% had used illicit substances such as cannabis, cocaine, and psychedelics, which they reported as effective in managing their symptoms. These early findings support further investigation into the therapeutic potential of psychedelics for treating functional neurological disorders and functional seizures.

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The promising results from these initial studies and patient reports underscore the need for more rigorous research to explore the efficacy and safety of psychedelic-assisted therapy in this context. This could lead to the development of new, more effective treatment pathways for individuals suffering from functional seizures and related conditions.

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Functional Seizures and the Potential of Psychedelic-Assisted Therapy

Functional seizures are complex and not fully understood, with various theoretical models proposed to explain their mechanisms. Researchers have explored the potential of psychedelic-assisted therapy as a treatment for functional seizures and proposed a roadmap informed by complexity science — a field that studies how interconnected parts of a system produce behavior that is more complex than the sum of its parts.

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Historically, functional seizures have been viewed as a release mechanism for trauma or psychological distress, previously categorized under terms like hysteria and conversion disorders. Modern models propose several explanations:

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1. Hard-Wired Response Model: functional seizures are seen as reflex-like, involuntary responses to perceived threats, akin to defensive reflexes like freezing.
2. Dissociative Model: functional seizures are thought to result from a dissociative breakdown of consciousness, memory, and perception in response to severe stress or trauma.‍
3. Learned Behavior Model: This model suggests that functional seizures develop through classical conditioning—individuals learn seizure-like behavior from observation, which is then reinforced by the temporary relief of distress (operant conditioning).

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The Integrative Cognitive Model (ICM), introduced by Reuber and Brown in 2017, integrates these theories. It suggests that functional seizures arise from the interaction of biological, psychological, and social factors, resulting in a learned pattern called the "seizure scaffold." This scaffold, influenced by reflexes, physical symptoms, and learned behavior, can be triggered by stress, trauma, or other stimuli, particularly when higher brain functions fail to inhibit emotional responses. The ICM proposes that functional seizures serve as an adaptive mechanism to mitigate hyperarousal.

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Functional MRI (fMRI) studies, which measure brain activity by detecting changes in blood flow, have identified changes in brain regions and networks in functional seizures patients, highlighting abnormalities in cognitive, emotional, attentional, and sensorimotor processes. However, these findings are often inconsistent.

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Understanding these complex mechanisms may allow researchers to use psychedelic-assisted psychotherapy to target the underlying brain networks involved in functional seizures, potentially providing a new and effective treatment approach.

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Understanding Functional Seizures Through Complexity Science

Functional seizures  can vary widely among individuals, and this variability can be better understood through complexity science. This interdisciplinary field studies how interactions among many parts create overall behavior in systems like brains and ecosystems. 

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From this perspective, functional seizures are seen as dynamic, whole-brain phenomena. The specific way functional seizures manifest in a patient depends on individual factors like their predispositions and stressors, making each person's brain interactions unique and changeable over time.

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Complexity science uses advanced methods to find patterns in these changing brain interactions, recognizing that brain connectivity varies over time and between individuals. This approach helps explain the differences in functional seizures symptoms and findings.

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For example, some patients might have brain activity driven by stress and hyperarousal, leading to increased connectivity between emotional and sensory regions. Over time, this can cause excessive inhibition by the prefrontal cortex, disrupting other brain regions and triggering a seizure.

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This view aligns with research showing that functional seizures often involve changes in top-down brain control and are linked to early adverse experiences, resulting in chronic stress and maladaptive brain connections.

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Overall, complexity science may help us understand the varied nature of functional seizures, viewing it as a feature of their neurobiology. This perspective is valuable for future research and treatment development.

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How Psychedelics Alter Brain Connectivity

Neuroimaging studies, particularly with fMRI, show that psychedelics cause complex changes in brain connectivity across almost all major brain networks. These changes typically result in more interconnected and flexible brain activity, allowing for greater adaptability and responsiveness. However, like studies of functional seizures, findings on psychedelic effects can be inconsistent and vary widely between individuals and studies.

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Dr. Manesh Girn, a leading psychedelic researcher and valued Webdelics advisory board member, proposes that psychedelics create a unique mode of brain function. Under psychedelics, the brain becomes less constrained and can explore a broader range of states, enhancing sensitivity to the surrounding environment.

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This framework emphasizes that the effects of psychedelics depend on internal factors (such as personality and emotional state) and external factors (such as the physical and social environment), collectively known as “set and setting.” As a result, brain connectivity patterns under psychedelics can be highly individual and change over time.

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Instead of looking for a sinmgle, static pattern of brain connectivity, researchers suggest using complex system analyzes to understand how brain connectivity changes dynamically during a psychedelic experience. These analyses can identify recurring patterns, their switching frequency, and the predictability or entropy of these patterns over time.

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The literature on psychedelics shows extensive brain interactions across various regions and networks. Complex system analyses may help unify inconsistent findings and reveal potential overlaps between the mechanisms of psychedelics and functional seizures. This approach might show whether the flexible brain states induced by psychedelics can disrupt the network dysregulation seen in functional seizures.

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Moreover, complex system analyses could help develop treatment strategies and evaluate psychedelic therapy outcomes for functional seizures, offering a new perspective on how psychedelics might benefit individuals with this condition.

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Psychedelic-Assisted Therapy as a Treatment for Functional Seizures

Psychedelic-Assisted Therapy involves the use of a psychedelic substance in a controlled setting with comprehensive psychological support before, during, and after the experience. This approach combines the emotional effects of the psychedelic experience with its biological impacts to encourage long-lasting positive changes in behavior and mental health.

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Psychedelic-assisted therapy addresses multiple factors — biological, psychological, and environmental — making it a potential adjunct treatment for functional seizures. It may help reduce functional seizures symptoms by treating co-occurring mental health issues and influencing brain networks related to functional seizures.

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The previously mentioned recent case report demonstrated the potential effectiveness of psychedelic-assisted therapy for functional seizures. Here, a patient with functional seizures, depression, and PTSD showed significant improvements after undergoing three weeks of Ketamine-Assisted Therapy (KAT). This regimen included three preparatory sessions, three ketamine sessions (via sublingual and intranasal administration), and three integration sessions. Following this, the patient continued with 20 weeks of ketamine maintenance therapy, incorporating Cognitive Behavioral Therapy (CBT), psychodynamic therapy, and mindfulness practices.

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Post-treatment, the patient experienced substantial reductions in the frequency and severity of seizures and improvements in depression and daily functioning, as measured by standardized scales. The patient also successfully reduced benzodiazepine use and was able to process trauma without triggering seizures during KAT sessions.

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These promising results indicate that psychedelic-assisted therapy could be an effective treatment for functional seizures and warrants further investigation to understand its mechanisms and broader potential for treating functional neurological disorder.

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Applying Complex Systems to Functional Seizure Treatment

The common thread amidst the diversity of functional seizures is that global brain dynamics function in a coordinated manner toward specific goals, but also share points of vulnerability. By applying complex system analyses, researchers may be able to gain novel insights into the overall patterns of neural alterations that underpin FS.

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These analyses may help identify how the brain's dynamic interactions contribute to FS and reveal potential mechanistic overlaps with the effects of psychedelics. Psychedelics are thought to alter fundamental properties of global brain dynamics, potentially helping to “reset” or deviate from dysfunctional patterns of functioning.

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By adopting a complex systems approach, researchers may be able to achieve a deeper understanding of the therapeutic mechanisms involved. This perspective could enhance our comprehension of how psychedelic-assisted therapy may be leveraged to treat FS, providing a more targeted and effective treatment strategy.

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In summary, the integration of complex system analyzes into the study of functional seizures and psychedelic-assisted therapy offers a promising avenue for future research. It has the potential to unify diverse findings, uncover the underlying mechanisms of both conditions, and ultimately improve treatment outcomes for individuals suffering from functional seizures.