Chronic pain is one of the most common and least discussed entry points into substance-related harm in the United States. Long before heroin or illicitly manufactured fentanyl appear in a person’s life, many people are simply trying to endure severe, persistent physical pain. Opioids have long been central to that effort. They are not a mistake. They are among the most powerful analgesics ever developed and remain indispensable in surgery, cancer care, trauma medicine, and some forms of chronic pain management.
The problem is not opioids themselves. The problem lies in how pain is managed, regulated, and constrained in the United States today.
I am writing in part from personal experience, as I lived with chronic pain for many years from my early 20s through most of my 30s. This also comes from years of study and involvement in this nascent space.
For many people living with chronic pain, long-term opioid therapy initially provides stability, functionality, and the ability to work, care for family, and participate in daily life. Over time, however, stigma, regulatory pressure, and fragmented care can erode that stability. Patients receiving chronic opioid therapy are increasingly viewed through a lens of suspicion and liability rather than continuity of care. Prescriptions may be tapered or discontinued abruptly. While this is improving in some places, clinicians still fear legal and professional consequences.
Patients fear being labeled, abandoned, or criminalized. This is often where risk meaningfully increases.
When people lose access to prescribed opioids, most do not immediately turn to heroin or fentanyl. Many first seek illicitly obtained pharmaceutical opioids: OxyContin and similar medications manufactured by pharmaceutical companies but sold outside the medical system. These substances feel familiar and, relative to non-clinical drugs, safer. The limiting factor is cost. Illicit pharmaceutical opioids are expensive, and maintaining a supply can quickly become financially unsustainable. (Worth noting that legal use of opioids contributes substantially to American overdose figures.)
As pain persists, tolerance increases, and access to consistent medical care diminishes, economic pressure intensifies. Cheaper alternatives become more attractive. Heroin and illicitly manufactured fentanyl are far less expensive and far more potent. They are also far more dangerous in this illicit context. This transition is rarely driven by recklessness or a desire to “get high.” It is more often driven by price, access, desperation, and untreated pain. This progression represents one of the clearest and most preventable pathways from chronic pain into high-risk opioid use and overdose.
These dynamics did not emerge in isolation. They are a predictable consequence of prohibition-based drug policy and aggressive criminalization of drug supply. In such systems, people managing pain are forced to navigate unstable and increasingly lethal markets rather than receiving long-term, adaptive care. Potency, unpredictability, and contamination become structural features of supply rather than exceptions.
Precision matters here. Opioids are not inherently the problem. Fentanyl is one of the most effective analgesics ever developed and remains indispensable in regulated medical settings. Risk escalates when people are pushed out of supervised care and into illicit supply chains that reward potency over safety.
What remains largely absent is a middle path: a pain-care model that recognizes opioids as valuable but incomplete tools, and that offers additional ways to reduce suffering without forcing patients into all-or-nothing choices.
This is where psychedelics warrant careful, serious consideration.
Psychedelics and Chronic Pain: Emerging Evidence
A growing body of scientific literature suggests that certain psychedelics may influence chronic pain intensity, pain perception, and functional outcomes when used carefully and in combination with adjunctive therapies. These effects appear to involve mechanisms distinct from opioids, including modulation of central sensitization, emotional processing, inflammation, and maladaptive fear–pain feedback loops that can entrench chronic pain states.
A comprehensive review by Castellanos et al. describes how classic psychedelics primarily act through serotonin 5-HT2A receptor agonism, initiating downstream processes associated with neuroplasticity, altered functional connectivity, and anti-inflammatory signaling (Castellanos et al., 2020). Chronic pain conditions, particularly centralized pain syndromes, are increasingly understood as disorders of maladaptive neural circuitry rather than purely peripheral injury. Psychedelics may temporarily destabilize rigid brain networks, allowing for reorganization toward less pain-dominant patterns.
Importantly, this review identifies conditions such as complex regional pain syndrome (CRPS), phantom limb pain, and other centralized pain syndromes as potential candidates for investigation. Large randomized controlled trials aren’t underway, but the biological rationale is coherent and consistent with contemporary pain neuroscience.
Case-Level Signals
Several published case reports and observational accounts help illustrate what an integrated, non-opioid-centered pain-care model might look like.
In one documented case, an individual experienced severe phantom limb pain following amputation, a condition closely linked to cortical reorganization and central sensitization. After participating in a structured program involving psilocybin alongside adjunctive therapies, pain intensity decreased substantially and remained lower over time. Similar outcomes have been reported in published cases combining psilocybin with mirror therapy for phantom limb pain (Ramachandran et al., 2018).
In another published case, a person lived with refractory complex regional pain syndrome for more than a decade, with pain consistently rated at extreme levels. Despite aggressive conventional treatments, including high-dose ketamine infusions, functional improvement was limited. Following a structured course involving psilocybin and adjunctive therapies, the individual experienced meaningful reductions in pain and regained previously lost functions, including driving and fine motor control. These outcomes align with a recent case report describing substantial functional improvement in refractory CRPS following psilocybin use (Jevotovsky, Wing et al., 2024).
Hear directly from the patient in this Psychedelics Today podcast.
These are strong signals. Signals that existing pain-care paradigms may be incomplete, and that additional tools deserve rigorous study.
Why This Matters
If psychedelic-assisted approaches can help even a subset of people with chronic pain reduce suffering and stabilize daily functioning, the downstream implications could be significant. Fewer pain patients would be forced into illicit markets and disability. Fewer overdoses driven by economic pressure rather than intent. Less family disruption. Lower long-term healthcare costs. A reduction in the quiet yet global, cumulative toll of unmanaged pain.
This work is being advanced by organizations such as the Psychedelic and Pain Association, which support interdisciplinary collaboration, research coordination, and responsible evidence-building around psychedelic approaches to pain. The goal is not to replace opioids or to romanticize psychedelics, but to expand the clinical toolkit with rigor, ethics, and care.
Pain is complex. Our responses to it must be equally nuanced. Continuing down the current path will perpetuate avoidable harm. A more skillful and compassionate future is possible, but only if we are willing to build it deliberately.
Donate to Psychedelics and Pain Association and join our newsletter here. The author is a founding board member of Psychedelics and Pain Association.
