Supporting research continuing to emerge
There have been some interesting trendlines emerging in research into psychedelics and their mechanisms of action. These trends mirror our own research into psychedelics and pain, as well as our experience in the NYU psilocybin trial for major depressive disorder. We have discussed these trends in various media, including interviews, articles, symposiums, our coursework, and interviews with noted experts and participants. If you search our Twitter feed, you will see a few key themes emerging in our threads and related news articles. A brief overview of them includes:
Visual field interactions with psychedelic-assisted therapy are often overlooked as major contributors to therapeutic outcomes. We know that visual field inputs, used in rehabilitation contexts for conditions like brain lesions, strokes, and TBI, can be effective drivers of recovery. Visual phenomena are a major part of the psychedelic experience and are often the central focus of people's accounts. This is consistent with our direct experience in the NYU psilocybin trial, as well as our prior training in applied neurophysiology for pain and performance issues.
The G.I. tract and enteric nervous system are replete with serotonin receptors. As we have stated in interviews and articles, we experienced significantly altered sensations in our gut for more than a month after dosing in the study trial.
Many neuropsychological disorders are also characterized by neuroinflammation and diminished immune response. Psychedelics, particularly psilocybin, are known to be potently anti-inflammatory. When we look at the psychological-physiological continuum, there is a bidirectional gut-brain interaction in the cortical-receptor loop. It is worth noting that indigenous practitioners often emphasize the importance of "dieta" in the preparation and integration of psychedelic journey work.
There is an effort to unify models of psychedelic pharmacological activity. The primary driver of change could be either the relaxation of top-down, strong priors within the cortical landscape or decreased thalamic gating of bottom-up sensory processing. The best outcomes of psychedelic-assisted therapy (PAT/PAP) likely depend on both being involved in a dialogical manner. For REMAP, both of these show great potential in explaining how psychedelics can resolve or relieve chronic pain. Top-down predictive processing errors and upregulated thalamic activity are both strong contributors to pain signals from the CNS.
Evidence is mounting that psychedelics can provide analgesic relief, even in microdoses. Microdoses may be effective in people with chronic pain, even if they don't have a significant effect on healthy individuals. Notably, the latest research strongly supports REMAPs protocol and our core idea of improving pain outcomes and others with psychedelic-assisted therapy.
Part of the process of recovering from pain involves rehabilitating injured structures and networks. Evidence suggests that psychedelics may be effective in creating neural reconnection in spinal cord injury survivors and others with lower-grade neural compromise. Neuroplasticity, and especially the neuro/metaplasticity generated by psychedelics, has been linked to increased spinal density, synaptogenesis, and dendritic arborization in VIVO. Our discussions with spinal cord injury survivor Jim Harris over the last two-plus years, our personal experience with intense tremoring creating neurological revision during the NYU trial, and evidence from veterans groups using psychedelics to treat combat-induced PTSD and TBI all point to this potential. Descending inhibition may also play a role in restoring sensory and motor control, as well as in inhibiting iterative rumination, which could be characterized as a type of nociceptive output of the CNS in conditions such as depression.
With all that in mind, let's highlight a few recent studies that illustrate potential mechanisms of action. We are looking at these from a global, systemic perspective. It will take multiple studies and years of research to gain a deeper understanding of specific mechanisms at a granular level. We'll start by examining visual field interactions and implications in this article.
Visual Field interactions
It's important to remember that the concept of neuroplasticity is still relatively new in the rehabilitative fields. As recently as 10 years ago brain and spinal cord injury was seen as often being intractable, and most rehab was based around adapting to it rather than repairing it. Things have shifted significantly since then and front-line best practices involve using multiple visual drills for TBI and other patients to maintain cognitive flexibility and visuospatial coordination. When we examine the neural hierarchy, it’s important to remember visual is at the top; visual, vestibular, and proprioceptive/interoceptive. When it comes to predictive processing/threat assessment, the visual system is absolutely key, with approximately up to 70% of our postural control coming from our eyes. The shortest neural arc in the human body is for the Vestibular Ocular Reflex (VOR); it’s incredibly rapid and crucial for our sense of orientation and where our head is in space. It allows you to keep your eyes fixed on a target as your head rotates through space. Visual stimulus is so integral to our survival that a couple of articles/studies back demonstrate this:
A study from the University of Washington reveals that cataract surgery is associated with a 30% reduction in dementia risk, which persists for at least a decade after surgery. Researchers hypothesize that people may receive higher quality sensory input following the procedure. This is just one example of visual neuromodulation having a direct effect on neural structures, quality of life, cognition, and longevity.
A randomized clinical trial published in the British Journal of Psychiatry, "Imagery rescripting and eye movement desensitization and reprocessing as treatment for adults with post-traumatic stress disorder from childhood trauma", revealed that reprocessing eye movements and imagery from Adverse Childhood Events (ACEs) that lead to adult PTSD can significantly reduce or resolve the condition.
In a paper that, quite honestly, we have been waiting for someone to write and publish, "More than meets the eye: the role of sensory dimensions in psychedelic brain dynamics, experience, and the therapeutics", Marco Aqil and Leor Roseman investigate whether the role of visual field dynamics during psychedelic-assisted therapy has been underestimated. Low-level visual sensory activity, such as geometric patterns, spirals, fractals, and figures, is likely due to pharmacodynamics. This is because these features are observed cross-culturally, do not occur with other hallucinogens, and suggest an underlying biological architecture to the visual phenomena, given the high density of 5HT2A receptors in the primary visual areas. Mathematical models show that much of the low-level visual phenomena seen under psychedelics can be explained by sensory oscillation dynamics due to receptor excitation within retinal mapping and occipital brain regions. This supports the thalamic gating camp's theory that the contributions seen in PAP are due to bottom-up sensory input no longer being filtered by the thalamus.
At the same time, higher-level dimensional phenomena, such as seeing deceased loved ones, fantastical animals, or scenes from one's personal past, are personally specific and thus not just “nonspecific amplification of ungated external sensory input”. This indicates that there is some kind of relaxation of higher-level dimension “strong priors” from visual interactions due to their personal intensity, novelty, and meaningfulness/saliency. All this is likely happening in a “dialogical” fashion, with bottom-up inputs and top-down relaxation of outputs interacting with and informing each other.This prospective study examines the effect of optical illusions on body parts in chronic pain. The article, "Distinct Neural Signatures of Multimodal Resizing Illusions: Implications for Chronic Pain Treatment", shows that multi-modal (visual and tactile) illusions have a stronger effect than illusory illusions alone. An example of an illusory illusion is the finger-stretching illusion.
Our previous discussions about phantom-limb pain and mirror-box/mirror visual feedback therapy (as seen in this tweet) have shown that people with chronic pain can have distorted mapping of body parts. Stacking a distorted/diminished sensory input with a strong/congruent one can create improvement in the former. Deliberately visually resizing such an area as part of a multi-system approach can create an exciting degree of neuroplastic improvement.Sometimes, the best way to improve an aberrant nociceptive output is to inhibit one of the inputs, particularly one as dominant as the visual field. There are many interventions that can be used to rehabilitate post-stroke and traumatic brain injury (TBI) patients through the visual fields, such as saccades, smooth pursuits, vestibular ocular reflex, and optokinetic. Sub-clinical deficits in these attributes can contribute to seemingly unrelated functional disorders. One unique application is called Bilateral Nasal Occlusion (BNO), which has been successfully used to treat veterans and other patients with TBI, stroke, or even cortical deficit issues arising from Long Covid.
Your vision is divided into multiple fields and pathways in each eye, which are fused and integrated with the visual input from the other eye in the occipital lobe. When the brain is in an inflamed state due to injury, illness, or dysfunction, visual stimuli can become provocative or aggravating to a hypersensitive nervous system. Interestingly, people with functional deficits or TBI often find BNO deeply relieving, while people with normal vision find it annoying and distracting.
Research has been conducted on these populations, such as Binasal Occlusion (BNO), Visual Motion Sensitivity (VMS), and the Visually-Evoked Potential (VEP) in mild Traumatic Brain Injury and Traumatic Brain Injury (mTBI/TBI). Rehabilitation and performance enhancement devices like Senaptec LCD strobe goggles can be used to target specific quadrants within each eye. Alternatively, scotch tape over empty frames can also be effective.In traditional indigenous and shamanic contexts, there is a great deal of visual, vestibular, and multi-modal neuromodulation occurring during the neuroplastic window. This is achieved through receptor layers, ascending, and descending pathways down in the cortical-receptor loop.
Rattles create tonal-topic mapping, while flickering firelight induces saccadic and optokinetic activity in the eyes. Smudging participants' bodies and limbs with a feather and smoke creates a stacked input of rapid visual movement, fluttering sound, and caressing the skin lightly enough to generate input on C-fibers subdermally without provoking a hyper-vigilant nervous system. This passes over the limbs and torso delicately, remapping the receptor layers' cortical representations with joy…during a non-ordinary state of consciousness, in a profoundly affirming community context, as the darkest universe splits itself open to welcome you to the light within.
Indigenous and shamanic communities have been running the longest observational A/B study on how the human nervous system responds under plant medicine for millennia.
It's important to understand that visual field modulation does not occur in isolation. As mentioned, the visual field, eye muscles, and eye nerves are closely linked to the brainstem and vestibular system, which is responsible for the sense of orientation in space. Loss of orientation can cause severe disorientation and distress, making it difficult to think. It can be seen as a form of nociceptive output, similar to tinnitus. Therefore, correcting, recalibrating, and rehabilitating the visual system can have a significant, cascading effect on our neurophysiology, across the physiological-psychological continuum, and make rapid changes to our homeostasis. Under the neuro/metaplastic window of a psychedelic non-ordinary state of consciousness, we have the opportunity to use visual neuromodulation to achieve remarkable therapeutic results; it would be a shame to leave so many tools on the table, unused.