Feeling Good with Narcotics Now “Evidence” of Opioid Deficiency: The Chemical Imbalance Theory of Depression, Redux

In a curious twist of the reformulation of the chemical imbalance theory of mood disorders – an idea that just won’t die – psychiatrists have turned their attention to depression as the result of a deficiency of endorphins. A recent randomized controlled trial compared the opioid partial agonist buprenorphine to placebo. The supposed success of the treatment in this studies led the authors  to conclude “these results support the hypothesis of a significant role of opioid dysregulation in major depression and the therapeutic potential of opioid modulation.” Put in plain terms, the astonishing conclusion is that people reporting feeling better with narcotics is “proof” that they have an opioid deficiency that justifies “treatment” with narcotics. It does not require a PhD in neuroscience to see why this claim is nonsense.

Backward Logic

The history of psychopharmacology is littered with examples of response to psychotropic drugs taken as evidence of drugs correcting some underlying disease state. In the early days of lithium in the treatment of manic-depressive illness, it was believed that such extreme mood states might be caused by a lithium salt deficiency. When it was discovered that the early antidepressant drugs inhibited the transporters of noradrenaline and serotonin, it was believed that deficiencies in these neurotransmitters might be the cause of depressive states. Similarly, when neuroleptics were discovered to block D2 dopamine receptors, hyperactivity of the dopamine system was hypothesized as the cause of psychosis.

This backward logic of presuming drugs are correcting an underlying disease process, rather than simply suppressing symptoms has been called the “disease-centered model” of drug action by psychiatrist Joanna Moncrieff. In the same way, taking depressed people feeling better with narcotics as supporting “opioid dysregulation” as the cause of their despair, is a remarkable feat of backward logic. It also highlights just how suspect previous claims have been. But this idea is even more pernicious because of the lethality of buprenorphine and the fact we are already in the midst of a prescription opioid epidemic.

The Dangers of Buprenorphine


Buprenorphine is already a blockbuster drug. It is the key ingredient in Suboxone and Subutex, popular office-based substitution therapies for people with opiate addiction. It was marketed as “non-abusable” as it is combined with naloxone, an opioid blocker, preventing users from injecting it. You can get “high” from it despite claims to the contrary, and it has significant abuse potential. People become dependent on it and buprenorphine addiction is real. It is fatal in overdose, especially when combined with alcohol or benzodiazepines. It is one thing to prescribe buprenorphine as opioid substitution and a harm reduction intervention to those already addicted to heroin and prescription narcotics. It is another thing altogether to prescribe it to opiate naïve individuals desperate for relief from emotional distress. Although the recent study found no evidence of withdrawal or dependence emerging, it was only 4 weeks long, which is far too short to identify these problems.

Reformulating Emotional Distress

In my clinical practice I see people who are desperately searching for relief from their pain. Sometimes I feel completely helpless as I bear witness to the intractable suffering that seems recalcitrant to any therapy. From this vantage point, it is easy to see the appeal of a pill that could rapidly lift interminable despair. The problem is we have redefined human emotions as something to be suppressed and eradicated, as lacking purpose and meaning. In my younger patients especially, I notice a trend to see powerful emotions as unacceptable, and to have unrealistic beliefs that we should be happy all the time. In our culture of a pill for every ill, emotions we don’t want can be obliterated on demand. We have lost our ability to tolerate distress, to find meaning in emotion, and purpose in experience. As the sociologist Nikolas Rose has noted, we have recoded our moods in terms of neurochemistry. Emotions no longer have context. They are aberrations in neurochemistry. I’m no longer hurting because I’m lonely, but because I’m running low on endorphins. Buprenorphine for depressive despair reinforces the belief that emotions should be obliterated, and can only be done so through modulating biochemistry.

Does it Even Work?

Although we can see how relief of depression by buprenorphine does not mean depression is caused by opioid dysregulation, let’s consider the actual study results. Much of the improvement seen in the study — as with other antidepressants studies — can be explained by placebo effects, regression to the mean (people feel better eventually anyway), contextual healing, and positive expectancy effects. Some of the difference can also be explained by the unmasking of the active drug vs. placebo by the terrible nausea and vomiting induced by the drug. In fact, those given a whopping 8mg dose (which is what you would start a prescription opioid addict on) did not seem to get the same positive effects as the 2mg group, presumably because they experienced too much dizziness, nausea and vomiting. But if we look at those given 2mg, they did not achieve the 50% reduction in depression scores that is typically defined as “response” in antidepressant studies. In other words, it doesn’t even work very well. Yet somehow the conclusion is: “these results support the hypothesis of a significant role of opioid dysregulation in major depression and the therapeutic potential of opioid modulation.” I think not.




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