Reconceptualizing Psychedelic Cognition and Neuroplasticity in Therapeutic Outcomes

Introduction

The therapeutic potential of psychedelic compounds for various mental health conditions is gaining significant attention. A prevailing hypothesis suggests these effects are mediated by meta-plasticity and neuroplasticity processes. Meta-plasticity describes the sensitivity with which an individual’s experience and exposure to environmental stimuli impact reward and association learning and is hypothesized to increase following the acute psychedelic experience. Neuroplasticity describes actual structural neural changes in the brain. While the acute effects of psychedelics are well-documented, the antidepressant and anxiolytic effects observed sometimes immediately post-session suggest that neuroplastic and meta-plastic changes may commence during the psychedelic state, rather than solely as a downstream consequence. This tendency converges with evidence of synaptogenesis that has been observed in mice within two hours of psychedelic administration. This raises a critical question: what types of cognition are preserved or enhanced via this psychedelic-induced plasticity?

Redefining Psychedelic Cognition

Understanding psychedelic cognition requires acknowledging the distinct ways “cognition” is defined across psychological disciplines. In Cognitive Behavioral Therapy (CBT), “cognitive” primarily refers to thought forms (cognitions and beliefs), including conscious, automatic thoughts, core beliefs (schemas), and cognitive distortions (e.g., catastrophizing). These are largely observable and reportable mental representations that directly influence emotions and behaviors, making them targets for conscious restructuring.

In contrast, neuropsychology defines “cognitive” as unobservable cognitive domains or functions—fundamental mental processes often viewed as brain functions. These include:

• Attention (sustained, selective, divided)
• Memory (working, verbal, visual, long-term)
• Executive Functions (planning, problem-solving, cognitive flexibility, inhibition)
• Language (expressive, receptive)
• Perceptual-Motor Control
• Processing Speed
• Social Cognition (empathy, understanding social cues)

Neuropsychology investigates how brain structures and functions underpin these abilities, using standardized tests to infer their functioning and identify deficits. While distinct in their practical application—CBT optimizes the “software” of thought processes, while neuropsychology diagnoses issues with the “operating system” of the brain—both types of cognition are likely involved in the psychedelic experience.

To better characterize the complex interplay of mental processes under psychedelics, we propose a three-factor understanding of psychedelic cognition:

1. Perception: The experience of novel objects of awareness or phenomenological content.
2. Cognitive Representations: Thoughts, beliefs, and insights (akin to CBT’s “cognitions”).
3. Cognitive Functions: Higher-order unobservable processes (e.g., meta-awareness, meta-cognition, meaning ascription, sentimental object relations, cognitive flexibility and perspective taking).

While many ordinary cognitive functions supporting daily survival are typically impaired during the psychedelic state, it is plausible that other, less well operationalized cognitive functions are strengthened. This temporary impairment of typical functions may paradoxically potentiate alterations at the cognitive representation level, allowing for more intensive mental processing of thought forms and beliefs, leading to the emergence and internalization of insights. The interaction between altered cognitive functions and cognitive representations with novel percepts can facilitate a holistic sense of symbolic meaning, a phenomenon observed to be particularly valuable in patients with post-traumatic stress disorder (PTSD).

Integrating Cognition, Plasticity, and Therapeutic Outcomes

A fundamental question arises regarding the optimal model for integrating psychedelic cognition with psychedelic-induced neuroplasticity/meta-plasticity and the observed pro-health effects. Many psychologists intuitively attribute pro-health changes primarily to insights (cognitive representations), especially given the perceived importance of post-session psychosocial integration. This model posits a causal pathway whereby cognitive representations lead to pro-health changes. We hypothesize that these insights may initiate neuroplastic processes and influence health outcomes during the psychedelic session itself, not just afterward.

Furthermore, we propose that specific cognitive functions, such as heightened meta-awareness and meta-cognition (the ability to consciously process mental representations and emotions), the ascription of significance/meaning to objects of awareness, and cognitive flexibility (in terms of repertoire of different perspectives), may also be preserved within future personality states via neurobiological plasticity processes.

A parallel can possibly be drawn from the pathogenesis of PTSD, where functions like attention and emotions (e.g., fear) persist as maladaptive hypervigilance, intrusive memories, hyperarousal, and fearfulness due to plasticity. Similarly, the preserved cognitive and physiological functions under psychedelics may directly contribute to pro-health effects, potentially as much as, if not more than, the insights themselves.

Further research is warranted to elucidate the precise interplay and relative contributions of these cognitive factors to the lasting therapeutic benefits of psychedelics. For example, alterations in cognitive functions and cognitive representations may interact with percepts during psychedelic experience (perception level) to deliver a holistic sense of symbolic meaning, which has been extremely interesting and valuable for some of our current patients with PTSD.

Key questions for future research?

Does meta-plasticity obtain during the acute effects of psychedelics in humans?

What levels of cognition (cognitive representation, cognitive function) contribute to enduring pro-health effects of psychedelics?

How specifically do neurobiological plasticity processes underlie enduring changes in cognitive representations and cognitive functions?