This theory-building paper (2020) introduces the ‘pivotal mental state’, a hyper-plastic state (as reaction to chronic and acute stress – or incited by psychedelics) which can mediate psychological transformation.
Abstract
“This paper introduces a new construct, the ‘pivotal mental state’, which is defined as a hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation. We believe this new construct bears relevance to a broad range of psychological and psychiatric phenomena. We argue that pivotal mental states serve an important evolutionary function, that is, to aid psychological transformation when actual or perceived environmental pressures demand this. We cite evidence that chronic stress and neurotic traits are primers for a pivotal mental state, whereas acute stress can be a trigger. Inspired by research with serotonin 2A receptor agonist psychedelics, we highlight how activity at this particular receptor can robustly and reliably induce pivotal mental states, but we argue that the capacity for pivotal mental states is an inherent property of the human brain itself. Moreover, we hypothesize that serotonergic psychedelics hijack a system that has evolved to mediate rapid and deep learning when its need is sensed. We cite a breadth of evidences linking stress via a variety of inducers, with an upregulated serotonin 2A receptor system (e.g. upregulated availability of and/or binding to the receptor) and acute stress with 5-HT release, which we argue can activate this primed system to induce a pivotal mental state. The pivotal mental state model is multi-level, linking a specific molecular gateway (increased serotonin 2A receptor signaling) with the inception of a hyper-plastic brain and mind state, enhanced rate of associative learning and the potential mediation of a psychological transformation.“
Authors: Ari Brouwer & Robin L. Carhart-Harris
Notes
The paper proposes a “multi-level, biologically informed, context-dependent and process-based” approach to psychological transformation (rapid and enduring change of worldview). The construct is informed by psychedelic research.
In the paper this is referred to as the ‘pivotal mental state’ (PiMS), with the following characteristics:
- elevated cortical plasticity
- enhanced rate of associative learning
- unique capacity to mediate psychological transformation
The construct is agnostic as to the outcomes (positive or negative) and the role of context: “We conclude this article by restating the principle that although PiMSs may be associated with major psychological change, the quality of such change is neither consistent nor predetermined. We propose that the surrounding context and relational frame in which a given PiMS occurs is a vital determinant of how it manifests.”
“This paper has proposed that certain traumatic, spiritual, psychedelic and psychosis-relevant experiences can be viewed as examples of what we call PiMSs: transient, intense hyper-plastic states of mind and brain that have the potential to mediate rapid, major and potentially enduring psychological change. Various stressors have been found to upregulate the 5-HT2AR system and converging evidence implies that increased 5-HT2AR signaling may be a key molecular gateway through which PiMSs arise. The pharmacology, systems-level neurobiology and phenomenology of the (5-HT2AR agonist) psychedelic drug state is treated as particularly informative in this regard.“
Summary
(Miller and C’de Baca, 2001, Quantum Change)
Psychological transformation is a phenomenon that has received little formal scientific investigation. This paper proposes a multi-level, biologically informed, context-dependent and process-based approach to the phenomenon, which identifies striking similarities in the conditions of induction, neuropharmacology, neurobiology and psychology of transformative experiences.
In the same way that traumatic experiences can trigger post-traumatic stress disorder or post-traumatic growth, intense periods of psychological crisis can kindle conditions for major, potentially lasting, psychological change.
This paper introduces a new construct, the pivotal mental state, which is defined as a hyper-plastic state aiding rapid and deep learning that can mediate psychological transformation. It is hypothesized that serotonin 2A receptor agonist psychedelics hijack a system that has evolved to mediate rapid and deep learning.
This review examines the nature and causes of PiMSs, and their close association with psychological transformation. It is mindful of the essential role played by context in shaping the quality and influence of PiMSs, and how context can be used to resolve the wellness versus pathology paradox.
If we are correct that context plays a key role in shaping the outcome of a PiMS, we should treat contextual factors with special attention and therapeutic care, whenever a PiMS arises or seems imminent.
The psychopharmacology of PiMSs takes centre stage in this article, which places special focus on the serotonin system and its 2A receptor (5-HT2AR) subtype in particular. Various acute stressors appear to be reliable and robust inducers of serotonin release.
There are many different types of stressors that can affect animals, such as sleep deprivation, hypoxia, chronic tryptophan depletion, inflammation, tonic pain, repeated forced swim, repeated shock, administration of stress hormones, amygdala stimulation, time-dependent stress, novelty stress, maternal separation, isolation rearing, and social defeat. All appear to upregulate 5-HT2AR expression, particularly in the cerebral cortex, which is well known to be massively expanded in humans.
Social isolation and defeat can sensitize behavioural responses to 5-HT2AR agonists, and direct agonism of the 5-HT2AR via psychedelic drugs can sometimes induce psychological states exhibiting phenomena that mimic those seen in extreme stress states.
We highlight several examples of how stress can be intentionally manipulated to promote endogenous psychedelic-like signaling for the purposes of personal and/or spiritual development.
Psychedelic drugs trigger conditions conducive to psychological transformation via their action at the 5-HT2AR, which in turn inspires research into the pharmacology and phenomenology of endogenously occurring PiMSs, including how it relates to mental illness and its treatment.
A review of the literature suggests that the 5-HT2AR is a key trigger site for inducing PiMSs, and that these mechanisms have evolved to aid rapid and deep learning in situations of perceived or actual existential threat or crisis.
Although PiMSs may be associated with major psychological change, the quality of this change is neither consistent nor predetermined. Therefore, engineering optimal contextual frames is essential for effective PiMS-related psychotherapy.
The PiMS model of mental healthcare focuses on psychedelic therapy as a prototypical PiMS-focused intervention, but there are other relevant examples. A growing appreciation of PiMSs may inspire a healthy pivot in mental healthcare and research, more firmly towards the biopsychosocial model.
Before reviewing relevant literature pertaining to the PiMS construct, it feels necessary to flag some of its complications, such as the potential for iatrogenic outcomes and the importance of contextual factors for safeguarding against harm and enhancing positive therapeutic outcomes.
We recognize the stabilizing influence of implicit assumptions on one’s mental state, and the potential risks of destabilizing such beliefs via the direct action of psychedelic drugs or other means.
The position that PiMSs are ripe mediators of psychological transformation, whether towards pathology or away from it, could be viewed as unjustly dismissive or neglectful of the important contribution made by factors such as polygenic predisposition and early life adversity.
A fork in the road or river analogy is often used to reflect a bifurcation process, where a system’s trajectory can rapidly destabilise and complexify at a point of bifurcation. Contextual factors can be viewed as biasing currents in the river influencing particular outcomes.
divergent outcomes
We argue that the 5-HT2ARR-mediated PiMS can mediate divergent outcomes that strongly depend on the surrounding context in which they arise. We apply this principle to a classic controversy in psychology and psychiatry: namely, the relationship between spiritual experiences and psychosis.
According to the model presented here, psychosis and spiritual experience are related to the PiMS.
Certain psychoses and spiritual or religious conversions share a common heritage in the pivotal mediational state, which is a relatively brief and intense root state that can mediate strongly divergent outcomes, such as spiritual or religious epiphany or conversion versus the acquisition of a psychotic delusion.
In this paper, we use a recent definition of stress that acknowledges how stress can engage adaptive mechanisms, such as heightened plasticity. This link between stress and adaptability can help us understand the etiological and evolutionary function of PiMSs.
Stress is typically felt as an aversive phenomenon, and PiMSs can often lead to negative outcomes. Adverse conditions are likely to mediate and/or potentiate PiMSs, and have all been significantly linked with psychotic disorders.
Spiritual and psychotic experiences can be emotionally antithetical, with psychotic experiences often feeling invasive and torturous, whereas naturally occurring and psychedelic-induced spiritual experiences can feel positive and euphoric.
Increased emotional tone is a common feature of PiMSs, and the duration of negative affect (but not its intensity) predicts negative long-term outcomes after psychedelic drug use.
Emotion can be thought of as prediction error modulating the precision of posteriors or priors. If the affective tone of a pivotal state is positive and intense, this may drive a ‘de-weighting’ or relaxation of a negatively held belief.
Increased emotional tone coupled with hyper-plasticity and enhanced associative learning can lead to the formation of affect-laden worldviews, which can explain how a consistent root state can mediate extremely divergent outcomes.
Manic states can be seen as a challenge to this rule, however, because they can exist in parallel and/or interchangeably with negative and positive mood states. Moreover, highly positively valanced mood states do not naturally imply positive long-term outcomes for mental health.
Psychotic episodes and spiritual experiences are both commonly preceded by a dissatisfaction with reality and one’s place within it. The transition into a psychotic episode or spiritual experience can be construed as a ‘manic defence’.
In longer prodromal states, a loss of interest in key activities and pursuits can coexist with an emerging interest in supernatural paranormal, religious and ritual domains, and a dissociation of subjective awareness from one’s body and/or thoughts.
Religious traditions may place value on understanding the nature of the self, its relationship to the world and its transformation, and may offer potentially useful frameworks for framing experiences that would otherwise be construed as pathological.
Serotonin, coping and adaptation
Serotonin is an endogenous monoamine found throughout the body, particularly in the gastrointestinal system, lungs and the central nervous system. It plays an important modulatory role in several key aspects of mind and behaviour, including brain development, mood, cognition, sleep and memory. Stress, pain and uncertainty are the most reliable inducers of 5-HT release, and it has been proposed that serotonin’s serenic effects may be a perceived as an adaptive response to adversity.
Stress avoidance/mitigation strategies may not be optimal long-term strategies, so it is reasonable to ask if there is an alternative adaptive mechanism that becomes triggered when adverse conditions surpass a critical threshold of severity and/or chronicity.
Stress primes the serotonin 2A receptor system for the elicitation of a PiMS, a state of cortical hyper-plasticity conducive to major adaptive change, such as post-traumatic growth after recovery from psychosis and other severe conditions.
The following questions will be addressed: Are certain stressors linked with the occurrence of states meeting the definition of a PiMS? Are 5-HT2AR-induced PiMSs associated with major psychological change or transformation?
Cognitive stress and the 5-HT2AR
A perceived lack of control is a well-known cause of stress, and may be a transdiagnostic factor in a variety of mental illnesses. The schizotypal mind may relieve itself by hypothetically solving matters of uncertainty via escape into fantasy or delusion, akin to the relief served by compulsive rituals in OCD.
Neuroticism and depression, indicative of chronic cognitive stress, regularly precede and coexist with psychotic disorders, and depression and despair often precede religious experiences. The 5-HT2AR is implicated in physiological and behavioural responses to chronic stress in humans and animal models.
Given the close association between depression and PiMS-related outcomes, it is natural to surmise that cognitive-stress-induced upregulation of 5-HT2AR expression may be an important biology x environment interaction through which both spiritual and psychotic experiences manifest via a subsequent increase in 5-HT2AR activation.
Psychological trauma predisposes certain individuals towards dissociation, hallucination and other psychotic-like features. The 5-HT2AR may mediate altered mind and brain functioning in relation to traumatic events, and may be involved in the action of psychedelics.
Social stress and the 5-HT2AR
Social stress and other relevant factors such as urban stress, ethnic minority status, migration, childhood trauma, poor cognitive aptitude and drug abuse have been linked with schizophrenia, as well as with higher rates of religious engagement.
Solitary confinement can lead to perceptual distortions, hallucinations, cognitive deficits and paranoia, and the classic 5-HT2AR agonist psychedelics quite reliably induce experiences of vivid sensed presence.
In preclinical modelling studies, 5-HT2AR antagonism impairs acquisition of conditioned defeat and suppresses hyperthermic response to social defeat, whereas 5-HT2AR agonist administration into the basolateral amygdala increases acquisition of conditioned defeat. Acute social defeat does not upregulate 5-HT2AR expression.
Maternal separation stress potentiates the effects of 5-HT2AR agonists and 5-HT2AR antagonists reduce maternal separation-induced anxiety, aggression and bradycardia. Isolation rearing likewise seems to upregulate 5-HT2AR expression and potentiate the effects of 5-HT2AR agonists.
The effects of isolation housing on 5-HT2AR expression are inconclusive and time variable, but it appears to potentiate 5-HT2AR agonist-induced wet dog shakes and head twitch in mature animals.
Physiological stress and the 5-HT2AR
Chronic inflammation, excitotoxicity, hypoxia, metabolic dysfunction, starvation, sleep deprivation and pain are all physiological processes linked to stress, and 5-HT2AR activation has neuroprotective and anti-inflammatory effects. This may explain why 5-HT2AR is upregulated by and mediates responses to so many stressors.
Hypoxia may be particularly relevant, as respiratory complications are associated with increased rates of psychosis, and hypercapnia may mediate the psychedelic-like effects of naturally occurring hypoxic conditions.
Hypoxia upregulates cortical 5-HT2ARs and DMT exerts neuroprotective effects in cells exposed to hypoxic conditions, leading scholars to suggest endogenous DMT may be released as an adaptive response to physiological stress. DMT may also play a role in NDEs.
Metabolic dysfunction and starvation are associated with psychotic phenotypes. Acute fasting and intermittent religious fasting increase 5-HT levels and metabolism, whereas longer-term tryptophan depletion or starvation may decrease 5-HT levels.
There is evidence of increased 5-HT2AR expression in overweight individuals and reduced 5-HT2AR expression in anorexia nervosa, but these decreases might be a compensatory long-term downregulation in response to chronic overactivation of 5-HT2ARs associated with restricted feeding.
Sleep deprivation is associated with increased 5-HT2AR expression and cortical 5-HT2AR binding, and both increases and decreases in 5-HT levels have been observed following sleep deprivation.
Severe and chronic pain are associated with psychosis, and the 5-HT2AR is involved in nociception and antinociceptive response in peripheral tissue, spine and brain in ways that are too nuanced for generalizations or coverage here.
The 5-HT2AR also plays a role in body temperature regulation, with agonists increasing core body temperature and antagonists blocking this effect. Some evidence suggests that exposure to heat or cold increases 5-HT levels, but other studies found no relationship between temperature manipulations and brain 5-HT levels.
Preliminary evidence suggests that decreased brain pH is an endophenotype for schizophrenia and bipolar disorders, and that 5-HT2AR agonism may be involved in the elicitation of psychedelic-like subjective effects by homeostatic imbalance caused by stress.
The link between stress and psychosis is well established, and the link between stress and spiritual experience may be less obvious, but it is supported by a wealth of evidence.
Intentional stress-induced pivotal mental states?
Humans have intuited how to hijack their own physiology for the purpose of self-development. Asceticism has an ancient history of association with altered states of consciousness.
Intentional social isolation, often in nature, is associated with spiritual and transformative experiences. Meditation on sin, guilt, death and suffering play a role in the spiritual exercises of various religious traditions.
Fasting and extreme moderation of food intake are common religious practices. Spiritual ‘athletes’ practice sleep restriction, promote night-time and/or early morning spiritual exercises, and in extreme cases, physically disable themselves from lying down.
Modern therapeutic techniques such as breathwork and whole-body hyperthermia reinforce the idea that physiological stress or dysregulation can lead to meaningful changes in mental states. Asceticism is a cross-cultural practice that may be associated with the emergence of a PiMS.
Ascetic practices may be protective against the derogatory and persecutory evaluations so integral to psychosis. However, the question of whether asceticism directly drives the occurrence of PiMSs may be solved by invoking bidirectional causality.
Evidence for ascetic-like behaviour being causative of PiMSs is provided by secular uses of stress to induce altered states, such as torture. It is also relevant that a significant history exists of combining torture, coercion and interrogation techniques with the administration of psychedelic drugs.
There is good reason to surmise that humans have an intuitive understanding of how to induce hyper-plastic mind and brain states. This realization has been exploited throughout the ages for self-development and spiritual or religious growth.
Psychedelics, psychopathology and spiritual experiences
Psychotic states are considered important examples of naturally occurring PiMSs, and classic 5-HT2AR agonist psychedelics are felt to be useful models of incipient psychotic states. Selective 5-HT2AR antagonism attenuates the main characteristic subjective effects of LSD, psilocybin and ayahuasca.
The 5-HT2AR is hypothesized to be involved in the induction of psychotic states, and dopaminergic dysregulation may serve as a ‘final common pathway’ underlying chronic psychoses. However, some evidence suggests that 5-HT2AR binding and blockade may contribute to the superior efficacy of atypical antipsychotics in attenuating positive and negative symptoms.
Serotonin 2A antagonism has less marked effects on cognition than 5-HT2AR agonism, but it can impair learning and promote compulsive behaviour. Therefore, it is possible that some of the therapeutic effects of 5-HT2AR antagonist antipsychotics may be due to a generic negative action on learning-related cognition and wakefulness.
In vivo imaging of 5-HT2AR binding in schizophrenia suggests decreased cortical receptor densities and downregulated 5-HT2AR mRNA and protein expression. This may be state specific, as healthy monozygotic siblings of affected persons do not display decreases in 5-HT2AR binding.
A cortical abnormality mediated by increased 5-HT2AR signaling and related glutamatergic activity, featuring abnormal plasticity and associative learning, may be an important early component of the psychotic process in schizophrenia. If we consider the pharmacology of the psychotic process via its phenomenology, then an initial state characterized by ego-disturbance and cognitive and perceptual disturbance preceding subsequent inflexible or perseverative cognitive and behavioural styles might fit with an initial serotonergic (5-HT2AR) component.
Psychedelics offer a reliable model of peak, god-encounter, mystical-type, near-death, and other anomalous experiences that bear an undeniable resemblance to experiences designated as ‘religious’ or ‘spiritual’. The 5-HT2AR rs6313 TT genotype is associated with trait absorption and altered time-perception in humans.
The psychology of the psychedelic state
Psychedelics induce cognitive-perceptual instability, relax one’s normal sense of agency and ownership over perceptual objects, and elicit an increased emotional lability. This allows bottom-up information to flow more freely up the brain’s functional hierarchy to impress on high-level cortices and enter conscious awareness.
The REBUS model is consistent with the phenomenology of the psychedelic experience, including intense spiritual, ‘peak’ or ‘mystical-type’ experiences. Such experiences may account for lasting psychological changes seen with psychedelics, such as increases in the personality trait ‘openness’.
Peak, mystical-type or spiritual experiences and associated feelings of oceanic boundlessness have been found to predict positive outcomes in psychedelic therapy, but may also represent an extreme experience only achievable through pharmacological manipulation.
Psychedelics may free suppressed emotions and memories so they can more easily percolate into consciousness awareness, allowing intense personal and transpersonal themes to rise to the forefront of awareness. This can foster an emotional re-evaluation of cognitive and philosophical perspectives that may have previously been closely tied in with a person’s pathology.
Psychedelic experiences can lead to increased willingness and ability to engage with emotionally difficult psychological material, enhanced sense of emotional empathy, and prosocial feelings and behaviour. However, extreme negative affect can also arise during psychedelic experiences.
The neurobiological effects of psychedelics
Functional brain imaging studies of psychedelic users have observed decreased modularity and reduced integrity of high-level networks, which may relate to high-level aspects of the drug-induced subjective experience, including ‘ego-dissolution’.
The increased global connectivity in the brain under psychedelics may be related to the weakening of discriminative cognition, exemplified by the unitive experience and ‘non-dual awareness’. This may also be a sub-acute effect of ayahuasca.
Psychedelics have been shown to promote extinction-learning through 5-HT2AR agonism, as well as low-level associative learning, as demonstrated by the catalysing influence of LSD on learning rate versus the impairing influence of ritanserin.
Consistently, psychedelics have been shown to potently increase cortical neuroplasticity, and psilocybin has been shown to increase visual evoked long-term potentiation (LTP) in healthy individuals and long-term changes in network functionality have also been observed 1 day, 1 week, and 1 month after psilocybin.
Increased brain complexity has been observed during rapid eye movement sleep, meditation, musical experiences and certain psychotic states, and is a reliable marker of the acute functional brain effect of psychedelics. This increased brain complexity may reflect a hyper-plastic state that mediates subsequent functional and potentially structural brain changes.
Certain types of stress upregulate 5-HT2AR expression and activity, and acute stress causes the release of 5-HT. The 5-HT2AR system is a stress response system that services adaptability.
The PiMS model proposes that the function of PiMSs exists to allow the experiencer a psychological ‘fresh start’, akin to a psychological ‘rebirth’ or allostatic recalibration. This process can be ‘positive’ (e.g. in terms of a therapeutic or spiritual breakthrough).
In extreme situations, such as a psychotic ‘flight from reality’ or progressive reinforcement of other psychological defence mechanisms, 5-HT2AR signaling may play a role in reconfiguring responses to environmental stimuli co-occurring with or preceding major perceived existential threats or crises.
Evidence of aberrant neuroplasticity in psychosis includes both increases and decreases in neuroplasticity markers, particularly during critical developmental windows. These increases and decreases may bear relevance to the reliable increases in plasticity linked to 5-HT2AR agonism.
Near-death experiences (NDEs) are relevant to the theory that the 5-HT2AR system has evolved to aid psychological transformation for adaptive ends. The major shifts in perspective following NDEs may be the product of a period of hyperplasticity, potentially mediated by either the massive release of 5-HT or indeed endogenous 5-HT2AR agonists such as DMT during the dying process.
A recent perspective on the evolutionary origin and potential treatment of PTSD is consistent with an earlier perspective piece on 5-HT2AR-mediated active coping and radical adaptation, as well as with animal work linking serotonergic functioning to faster learning rates. The 5-HT2AR-mediated active coping model (PiMS) maintains that the relationship between stress and upregulated 5-HT2AR signaling is non-linear, and that increased 5-HT2AR activity and associated plasticity are necessary for radical psychological change when its need is perceived.
The hierarchical predictive processing model posits that the brain evolves into a predictive model of the environment it inhabits, and that the de-weighting of internal predictive models under psychedelics opens a window for their subsequent revision.
Major recalibrations to fundamental beliefs or outlooks have been referred to as psychological ‘transformations’ or ‘rebirths’. The present PiMS model extends this previous (largely phenomenological) work by proposing a plausible mechanistic account for these phenomena.
Therapeutic implications
This review examines the potential causes, mechanisms and functions of the PiMS, a new psychological and neurobiological construct. It is our view that the PiMS represents a more fundamental state, and that psychedelics hijack this natural system to mediate psychologically transformative change.
Psychedelic therapy is showing promise for the alleviation of a large number of psychiatric symptoms and unhealthy lifestyle habits, and is often achieved via a small number of isolated therapeutic sessions, supported by subsequent psychological integration work.
Present findings indicate that psychedelic therapy may be used to treat diagnosed psychiatric illness as well as promote psychological wellbeing, including resilience-related changes. This suggests that psychedelic therapy may be used as a prophylactic or preventative intervention.
There are emotional pros and cons to recognizing PiMSs as important states of mind and brain, and it may be preferable to maintain strong distinctions between spiritual experiences and psychotic episodes and reject or ignore some of the similarities.
We anticipate some pushback to what is essentially a secular, naturalistic/scientific approach to phenomena others might consider ‘supernatural’, but we must be mindful of how an excessive recourse to the rationalism of science could promote a ‘cognitive fusion’ working against rather than for psychological flexibility and associated wellbeing.
We have placed significant emphasis on the 5-HT2AR system throughout this paper, but it should be acknowledged that MDMA and ketamine are also relevant examples in this regard. The duration of the therapeutic response associated with classic psychedelics appears to exceed that associated with a single exposure to ketamine.
If increased 5-HT2AR activity is a particularly robust and reliable inducer of PiMSs, then blocking the 5-HT2AR might make transformative psychological change less likely, and thus, making the medicated person vulnerable to relapse if the stabilizing medication is withdrawn.
Although untreated psychoses render an individual more susceptible to relapse, recurrent psychotic episodes serve to further reinforce illness chronicity. It is also debatable whether the incipient phase of a recurrent psychotic episode that emerges inadvertently, with few warning signs, represents a viable situation for (psycho)therapeutic intervention.
Limitations
This paper is a theoretical piece with a narrative style, which sacrifices self-critique and counterargument in favour of placing the spotlight on supportive evidence. It is inevitable that some truncation and oversight of relevant material has occurred.
This paper’s focus on a small number of example PiMSs could also be questioned, as it is based on a wealth of research on psychosis and its comparison to spiritual experiences. However, other states could have been considered, such as REM sleep or dissociative identity disorder.
We acknowledge that genetic and neurodevelopmental factors can influence the occurrence and outcome of a psychotic disorder, and we hope that this review will increase interest in translational research.
We focused on the 5-HT2AR system because of the wealth of supportive evidence for its association with PiMS-relevant phenomena. Other neurotransmitters such as noradrenaline, acetylcholine, glutamate, dopamine, the endocannabinoid and opiate systems will likely play a role in shaping the quality of PiMSs.
Infancy and childhood might be considered pivotal mental phases, and ‘microdosing’ with psychedelics might be considered another valid example of a pivotal mental phase.
The PiMS model could be applied to processes of ideological radicalization and deradicalization, and is consistent with the ‘Decentring’ model of religious experience and the social defeat hypothesis of schizophrenia.
Stress can increase 5-HT2AR expression and signaling, which can lead to increased cortical plasticity. However, stress can also negatively impact neuronal integrity and cause functional impairments, which need to be addressed if not reconciled.
One other point of critique is that the PiMS merely repackages previously introduced psychological constructs such as ‘quantum change’ and ‘transformative experiences’. We feel there is a great deal of scientific and pragmatic value in focusing more on the psychological and neurobiological nature and function of an outcome agnostic, yet pivotal, mediating state.
The psychedelic state meets all three defining properties of a PiMS, but more research is needed to demonstrate what the PiMS is not. This research should use stress-induction paradigms that are proven to reliably upregulate the 5-HT2AR system in non-human animals.
Conclusion
This paper has proposed that certain traumatic, spiritual, psychedelic and psychosis-relevant experiences can be viewed as examples of PiMSs, which are transient, intense hyper-plastic states of mind and brain that have the potential to mediate rapid, major and potentially enduring psychological change.
Religious traditions provide useful resources to prepare and guide individuals through psychological crises, including psychedelic therapy. In modern secular environments, we lack the same quality of integrated support, shared values and unified vision.