There is a conceptual inconsistency in contemporary medicine that I have become increasingly unable to reconcile. Psychiatry recognizes psychic pain as a genuine clinical phenomenon, and suicidology has long recognized unbearable psychological pain as integral to suicidal states. Neuroscience has simultaneously demonstrated that nociception, affective pain, reward, motivation, salience, stress responsivity, and emotional regulation are interconnected biological processes.

Yet when psychic pain becomes intolerable, psychiatry has remarkably little therapeutic infrastructure directed specifically toward alleviating the pain itself.

I approach this problem as both a psychiatric nurse and a patient. I was first diagnosed with psychiatric illness at thirteen and am now fifty-two. During nearly four decades of treatment, I have taken antidepressants from virtually every major pharmacologic class, antipsychotics, mood stabilizers, anxiolytics, stimulants, and numerous augmentation agents. I have also undergone ketamine treatment. I continued trying because I wanted to recover.

My most disabling illness has been severe body dysmorphic disorder (BDD). Describing BDD merely as preoccupation with perceived defects in appearance inadequately represents my experience. At its most severe, it resembles a pathological alteration in attention, salience, and self-referential processing. My face, body, and imagined appearance through other people’s perception become dominant objects of consciousness. Attention that should be available for other people and the external environment becomes captured by the self.

The resulting psychic pain can become extraordinary. I have experienced a bowel perforation, which provides a meaningful reference point for extreme physical pain. At its most severe, my psychiatric pain has exceeded even that.

This matters particularly in relation to suicide. Edwin Shneidman, one of the foundational figures in suicidology, used the term “psychache” for intolerable psychological pain and argued that suicide emerges when suffering becomes unbearable. Subsequent research has repeatedly associated mental pain with suicidal ideation and behavior. The clinical problem, therefore, cannot be reduced to a simplistic neurotransmitter narrative. A person experiencing suicidality may be attempting, above all, to escape an intolerable state of consciousness.

Why, then, do we treat physical and psychic pain as though one is genuinely pain while the other is merely a symptom?

They are not neurologically identical, but neither are they biological opposites. Conscious pain incorporates affective, motivational, cognitive, and salience components. The anterior cingulate cortex, insula, amygdala, and prefrontal systems participate in processes relevant to both pain and psychiatric suffering.

The endogenous opioid system occupies a particularly intriguing position within this intersection. OPRM1 encodes the μ-opioid receptor, and μ-opioid signaling participates not only in nociception but also reward, motivation, stress responsivity, and affective processing.

I carry the OPRM1 A118G polymorphism. A single polymorphism cannot explain a complex psychiatric phenotype, but research involving A118G has identified differences in μ-opioid receptor biology and aspects of pain and emotional processing. In the context of my own treatment response, that finding deserves curiosity rather than genetic determinism.

Opioid agonism has produced one of the most striking changes in my psychiatric suffering that I have experienced. I do not experience the effect primarily as euphoria. I experience normalization.

My appearance does not change. Its pathological salience changes. Relentless surveillance of my face and body diminishes. I stop continually imagining myself through other people’s perception. Internal criticism recedes, attention moves outward, curiosity returns, and social interaction becomes possible without simultaneously observing myself interacting. For years I have described the experience as finally fitting inside my own skin.

If pharmacologic manipulation of a receptor system reproducibly changes affective pain, pathological self-salience, attention, and social engagement, something biologically meaningful has occurred. Could altered endogenous opioid signaling contribute to intolerable psychic pain in some patients? Could μ-opioid receptor activation temporarily compensate for such an abnormality? These are empirical questions deserving investigation.

They are also not new questions. Opiates were used for melancholia long before modern antidepressants existed and remained part of psychiatric therapeutics into the twentieth century. In 1995, J. Alexander Bodkin, MD, and colleagues at McLean Hospital and Harvard Medical School investigated buprenorphine in patients with treatment-refractory major depression and documented substantial antidepressant improvement among patients who had previously failed or could not tolerate conventional treatments.

Robert T. Cochran Jr., MD, approached the subject through another clinical pathway. After decades treating chronic pain, Cochran observed psychiatric changes in patients receiving opioid treatment and developed those clinical observations in The Opiate Cure: Pain and the Bipolar Spectrum. Bodkin and Cochran approached the problem differently, but both confronted an important question: Why can manipulation of the opioid system profoundly alter psychiatric symptoms in some patients?

Contemporary neuroscience gives us better tools with which to answer it. The appropriate question is not whether psychiatry should recreate nineteenth-century opium treatment. It is what historical observations, modern clinical research, and contemporary neurobiology reveal about endogenous opioid signaling in psychiatric suffering.

Pharmacokinetics should also be investigated rather than treated as incidental. Duration of action, receptor occupancy, intrinsic activity, elimination kinetics, and gastrointestinal exposure all matter. μ-opioid activation within the gastrointestinal tract reduces motility and can produce substantial opioid-induced bowel dysfunction. Research should determine which receptor profiles and pharmacokinetic characteristics best provide therapeutic benefit while minimizing adverse effects rather than presuming that one formulation or duration is optimal for every patient.

Perhaps future treatments will involve partial agonists, receptor-selective compounds, biased ligands, endogenous opioid modulators, or mechanisms not yet conceived. The scientific objective should be to understand what produces relief and determine how that mechanism can be engaged as precisely and safely as possible.

Palliative medicine already recognizes an analogous principle. When disease cannot be eliminated, medicine does not abandon its obligation to relieve suffering. Preservation of function, autonomy, and quality of life remain legitimate therapeutic objectives.

Psychiatry needs an equally mature framework for severe, persistent, and treatment-refractory psychic pain.

After nearly four decades of treatment, I would still welcome a cure. What I reject is a risk-benefit analysis that scrutinizes the morbidity of treatment while treating the morbidity of undertreatment as a neutral baseline. Inability to work is morbidity. Social isolation is morbidity. Becoming unable to leave one’s home is morbidity. Psychic pain so severe that death begins to appear preferable to continued consciousness represents morbidity of the gravest kind.

My OPRM1 genotype is not the answer. My pharmacologic response is not the answer. Neither Bodkin’s research nor Cochran’s observations provide the entire answer. Together with the historical record and contemporary neuroscience, however, they provide compelling reasons to continue asking the question.

A patient should not have to develop cancer before relief of unbearable suffering becomes a legitimate medical objective. When psychiatric illness remains refractory, medicine’s responsibilities must extend beyond another iteration of an exhausted treatment algorithm. They must include serious investigation of the biological mechanisms generating psychic pain and a commitment to restoring the greatest attainable degree of function, autonomy, quality of life, and capacity to continue living.

Michelle Wyrick is a psychiatric nurse.