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 remain indispensable in surgery, cancer care, trauma medicine, and some forms of chronic pain management.
The problem is not opioids themselves. The problem is how pain is managed, regulated, and constrained in the United States today.
I write in part from personal experience. I lived with chronic pain for many years, from my early 20s through most of my 30s. I also write from years of study and work in this field.
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, stigma, regulatory pressure, and fragmented care can erode that stability. Patients on 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. This is improving in some places, but clinicians still fear legal and professional consequences, and patients fear being labeled, abandoned, or criminalized. This is often where risk meaningfully increases. The evidence bears this out: a 2021 JAMA study found that patients on stable, long-term opioid therapy who were tapered had a 68% increase in overdose events and roughly twice the rate of mental health crises compared with patients who were not tapered, with the greatest risk among those facing faster reductions and higher starting doses. A 2022 follow-up found the elevated risk persisted up to two years after the taper began.
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 made 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.
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. It is 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 treats 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. Not as a fix for the overdose crisis, and not for everyone in pain. The evidence so far is narrow, and it is worth being precise about what it actually covers.
Psychedelics and Chronic Pain: What the Evidence Shows
The published work on psychedelics and chronic pain is still small: a handful of mechanistic reviews and individual case reports, with no large randomized controlled trials completed to date. Within those limits, certain psychedelics may influence pain intensity, pain perception, and functional outcomes when used carefully alongside adjunctive therapies. The proposed mechanisms are distinct from opioids and include modulation of central sensitization, emotional processing, inflammation, and the maladaptive fear-pain feedback loops that can entrench chronic pain.
A review by Castellanos et al. describes how classic psychedelics act primarily through serotonin 5-HT2A receptor agonism, initiating downstream processes associated with neuroplasticity, altered functional connectivity, and anti-inflammatory signaling. 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 reorganization toward less pain-dominant patterns.
The review identifies conditions such as complex regional pain syndrome (CRPS), phantom limb pain, and other centralized pain syndromes as candidates for investigation. The biological rationale is coherent and consistent with contemporary pain neuroscience, but it remains a rationale, not a result.
Case-Level Signals
A few published case reports 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 a structured program involving psilocybin alongside adjunctive therapies, pain intensity decreased substantially and remained lower over time. Similar outcomes have been reported combining psilocybin with mirror therapy for phantom limb pain.
In another 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 treatment, including high-dose ketamine infusions, functional improvement was limited. Following a structured course involving psilocybin and adjunctive therapies, the individual reported meaningful reductions in pain and regained previously lost functions, including driving and fine motor control. These outcomes align with a 2024 case report describing substantial functional improvement in refractory CRPS following psilocybin use. Hear directly from the patient on the Psychedelics Today podcast.
These are signals, not proof. They suggest existing pain-care paradigms may be incomplete and that additional tools deserve rigorous study. They do not establish that psychedelics work for chronic pain at scale, and they say nothing yet about the much larger population caught in the opioid pipeline described above.
That gap is the point. Even if psychedelics eventually help a subset of patients with centralized pain, the people most exposed to overdose are not waiting on a new molecule. They are waiting on a system that does not push them off prescribed medication and into a contaminated illicit supply. The case for studying psychedelics seriously and the case for fixing pain care are related but separate, and conflating them helps no one.
One caveat worth keeping in view: this research is early and concentrated among a small, overlapping group of clinicians and advocates, several of whom are affiliated with the organizations now advancing the work.
This work is being advanced by organizations such as the Psychedelics & Pain Association, which supports interdisciplinary collaboration, research coordination, and responsible evidence-building around psychedelic approaches to pain. The goal is not to replace opioids or to romanticize psychedelics. It is to expand the clinical toolkit with rigor, ethics, and care.
The current system pushes people in pain toward the most dangerous drug supply available, then treats the result as a failure of character rather than policy. Any serious alternative has to start there. Psychedelics may turn out to be one piece of that alternative. Right now they are a research question worth funding, not an answer worth selling.
Donate to Psychedelics and Pain Association and join our newsletter here. The author is a founding board member of Psychedelics and Pain Association.
