What might it look like if someone had an imbalance between these two opioid systems — if perhaps they had too much of one or a paucity of the other or a defective receptor? This could theoretically occur as a result of environment — trauma, for example, or chronic stress — or from a genetic problem or some combination.

One result might be a depressive syndrome that is not responsive to the antidepressants now in use. There is little doubt that the current medications are inadequate for a significant portion of the population. A large study funded by the National Institute of Mental Health found that the rate of remission after two rounds of drug treatment was about 50 percent. After four rounds, around 30 percent of patients still suffered from depression.

Essentially, all the anti-depressants now in use affect a single group of neurotransmitters called monoamines and are likely to treat only specific subtypes of depression. Clinicians and scientists alike are in agreement that other pathways in the brain that control mood need to be explored. The opioids are one such pathway.

One “natural,” nonmedicinal use of opioids for depression is already widespread. There is a generally accepted hypothesis that long distance running produces a “runners’ high” via the production of endorphins, one of the brain’s opioids. Intense exercise is often “prescribed” for the treatment of depression. I have had several patients over the years whose lives revolved around punishing exercise schedules. On days when they could not exercise, they often experienced feelings of malaise and low mood — not unlike patients who miss a day or two of their antidepressants.

A medication that modulates the opioid system, buprenorphine, already exists, but is approved for the treatment of opioid addiction. Its actions are incompletely understood, but it is thought to block the opioid receptors that cause depression and only partly activate the receptors that enhance feelings of well-being, thereby blunting the high of drugs like morphine.

Whether buprenorphine will prove to be an effective and nonaddictive treatment for depression is unclear. Small studies of patients unresponsive to regular antidepressants have been encouraging — including a recent one in which very low-dose buprenorphine given for four weeks reduced suicidal thoughts in dangerously depressed patients. Research with larger numbers of patients and longer-term follow-up is needed before such medications can be recommended for clinical use.

Opioids may also hold out hope for a devastating illness formally known as borderline personality disorder. Characterized by severe emotional dysregulation, patients with this disorder have feelings of loneliness, rejection, anger and sadness that can quickly overwhelm them. They struggle to maintain relationships and are terrified of abandonment. They are often substance abusers and — in fact — opioids are frequently their drugs of choice. In one study, 44 percent of patients seeking buprenorphine treatment for their opioid addiction were found to have borderline personality disorder.