Psychedelics & Pain

Pain is often invisible - but the suffering is very real.

Pain is under-researched, under-treated, and minimized by society.

People living with pain deserve respect and a medical system that makes all treatment options available to them.

Pain is a complex and active ecology.

There is no single definition or manifestation of pain or chronic pain.

Pain can be both a symptom and a disease.

Primary pain is a disease unto itself (ie: migraine, cluster headache, CRPS). Secondary pain is a symptom resulting from another disease process or nervous system dysfunction (ie: peripheral neuropathy in diabetes, phantom limb pain, post-surgical pain). In some cases, secondary pain can maladaptively transition to primary pain (e.g. pain from spinal injury persisting past the healing period). This is where psychedelic medicines may be helpful in resetting and reducing pain.

Chronic pain serves no survival function in some circumstances.

Pain output, or intensity, should be a short term “alarm” aimed at preserving life. With chronic pain, this intensity can persist well beyond healing, deeply degrading quality of life and serving only maladaptive purposes.

Some pain is a perception.

Some pain can persist long enough to generate structural changes in our processing networks, so overwhelming them with signal that any input (ie. stimulation) can cause the central nervous system to fire off pain pathways. In this way, normal reflexes can become maladaptive and painful.

Pain is highly contextually dependent and can be a neurological disorder in and of itself.

We each experience pain differently — an extreme pain for you might be a minor bother for another. Pain has both external and internal (think: psychological) factors that can modulate the felt intensity of pain perception. Some pain (like migraine, CRPS, or cluster headache) can be entirely “organic,” non-injurious disorders of the nervous system. Likewise, these types of pain may develop subsequent to injury or surgery and represent pure neurological dysfunction.

Some pain exists in the total absence of injury, disease, or in the post-recovery period when healing is “complete.”

Extremely prevalent, fibromyalgia is an example of pain signals firing when no “injury” is present. In fibro, the normal aches and pains of daily life, most commonly resolved with movement, become chronic, exaggerated, and debilitating. Whatsmore, this type of pain can gather features bodywide, taking on new characteristics: cognitive deficits, depression, gut impairment, etc.


We need updated models for addressing pain.

Previous pain models do not fully address the complexity of pain, nor the differences in severity, duration, & scope from one individual to another, even with the same pain condition.

Cartesian Model

Developed in the 1600s, assumed that all pain symptoms were the result of tissue damage.

Pain Neuromatrix Model

These neurosignature patterns may be triggered by sensory inputs.

Bio-Psycho-Social Model

This model of pain is more comprehensive including psychological and social aspects.

Psychedelic Medicine for Pain

Psychedelic medicines will play a role in expanding the scope of treatment and understanding of complex pain.

Psychedelics are powerfully effective via their neurological mechanisms of action in treating chronic pain AND they can also address other key intrinsic factors: psychological & social contributors that strongly influence the intensity of pain perception and output as we now understand them through the Bio-Psycho-Social and Pain Neuromatrix model.

Key Mechanisms of Action

The complexity of pain is well matched by the multiple and complex ways that psychedelic substances can impact human physiology and perception. Psychedelic medicines have a number of biological effects that can reduce or prevent pain, such as the anti-nociceptive and anti-inflammatory impacts that many studies have identified. Psychedelics can also create neuroplasticity that enables people to alter and improve their relationship to the pain they experience.

New mechanisms of action for how psychedelics improve pain are continually being discovered and proposed. Mounting evidence seems to show that a confluence of biological, psychological, and social factors contribute to the potential of these medicines to treat complex, chronic pain. It is premature to state that there is one key or overarching mechanism. We support continued research to explore different ways that various psychedelics impact the wide range of pain conditions.

Below is a summary of the key mechanisms of action that are currently proposed for how psychedelics reduce pain and suffering. These concepts are presented discretely for clarity – but they almost certainly occur concurrently, interact dynamically and have impact synergistically.

Experience Mediated / Psychological Reframing

This pared down state may allow individuals to distance themselves from identification with pain, disability, and demoralization…

Thalamic Gating

The thalamus is a critical structure in processing noxious (harmful, unpleasant) input and regulating pain output…

5-HT2A Gene Polymorphisms

Research suggests that psychedelics may treat chronic pain by targeting, and activating, the 5-HT2A receptor…

Modulating Functional Connectivity in the Brain

Brain functional connectivity (FC) refers to the patterns of communication between different brain regions and structures…

Modulating Gene Expression

Psychedelics may treat chronic pain by modulating gene expression, either by decreasing or increasing expression, or activation, of certain genes…

Modulating Inflammation

Recent studies in animal models have shown the remarkable potential of psychedelic medicines to normalize body-wide levels of inflammation and to modulate the immune response…

Inhibitory 5HT Pathways

Psychedelics may turn on the body’s natural pain-relieving function by activating descending inhibitory 5HT (serotonin) pathways…

Inflammation, Autoimmunity, & Psychedelics

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