What Makes Opiates So Addictive?
Ever wonder about the science behind opiate addiction? Find answers here.
Posted Oct 09, 2018
For those who’ve experienced the legendary tow of opiates, a deepening cycle of despair and deliverance is commonplace. For the rest of us it is hard to imagine what motivates such futile and self-destructive behavior.
Through a neuroscientific lens, opiate addiction is as predictable as the cycle of day and night: euphoria leads to longing; relief predicts torture. This ping-pong living quickly becomes the status quo, as formerly surfeit doses of narcotic no longer do the trick.
All narcotics, including morphine, oxycontin, heroin, fentanyl, carfentanil, and whatever is next to arrive to market, produce their profound effects by trespassing in existing neural processes. They act as imposters at opioid receptors, the proteins on the surface of brain cells put there by evolutionary imperatives designed to keep us alive, and fecund.
Anything that impeded our ancestors’ ability to hunt, gather, or procreate would increase chances of extinction, both for individuals as well as the species. Over time, nature provided a veritable pharmacopeia of opiate-like compounds that help us overcome such impediments.
These natural comfort-givers are synthesized and released to mitigate a tremendous range of physical, emotional and psychological insults, and we’d surely be less content without them. Given that, it might seem reasonable to boost our natural physiological response by delivery of super-potent or time-release formulations in cases of intense but acute pain, or even where the ability to effectively raise doses will outlast the lifespan. In these cases, opiate drugs remain the gold standard for relief.
But the capacity to supplement our natural neurochemistry with drugs enables us to go further. All sorts of discomfort can be smoothed over by taking these drugs in moderate doses, and higher ones will not only level out the low spots, but produce an oceanic state of blissful contentment. Feelings of disappointment, frustration, or regret recede from awareness; the drugs immunize users from the relentless stream of daily stressors, superficial wounds, and prickly social interactions.
Though the idea of preventing all pain and suffering may seem appealing, as with unmitigated pain, a perpetually buffered existence would also compromise survival. Pain both impedes and facilitates well-being. It’s counterproductive in situations that would benefit from fighting or fleeing, but this advantage is temporary. Once the challenge has passed, if we remain oblivious to our hurts, we’d be unlikely to recover, or to learn from them.
From this perspective, it’s fortunate that our nervous system also deploys an arsenal of anti-opiate strategies, ensuring that we don’t miss the learning opportunities resulting from pain and discomfort. In this way, the brain is capable of fine-tuning pain states: tamping down in times of danger or acute challenge and cranking up at times when paying attention to the message is exigent.
This is ingenious if the goal is survival, but terrible news for anyone desiring to obviate pain and suffering in the long run.
Adaptation is arguably the brain’s most impressive feature, and for those whose discomfort compels an attempt to seek relief in a pill or a shot of opiates, the effects become more and more elusive. The more opiates one imbibes, the more the brain adapts to counteract their effects. Not only do regular users rarely get high, they experience increased pain, as the brain creates the state that drugs were used to address.
Like a thirsty man gulping down saltwater, opiate administration provides transient relief, but also strengthens the opposing state. Acute effects of opiates like analgesia, euphoria, sleep and constipation, are met by the brain’s opposing responses of pain, misery, insomnia and diarrhea. The solution of course is more opiates, and so the cycle deepens. Soon the user is marooned on a high wire between overdose and misery.
We are all susceptible to the lure of using psychopharmacological tools to medicate away unpleasant experiences. The desire to escape suffering is universal. From my perspective as a neuroscientist, it seems entirely unlikely that a drug capable of out-smarting the brain’s
adaptive prowess will be developed any time soon. However we choose to respond to the opioid epidemic in the meantime —whether in our homes or those of our neighbors—we’ll need to find more effective ways to cope with the pains of living.
Trescot, A.M., Datta, S., Lee, M., Hansen, H. (2008) Opioid pharmacology. Pain Physician, 11:S133-153.
Pasternak, G. W., & Pan, Y.-X. (2013). Mu Opioids and Their Receptors: Evolution of a Concept. Pharmacological Reviews, 65(4), 1257–1317. http://doi.org/10.1124/pr.112.007138
Koob, G. F. (2008). A Role for Brain Stress Systems in Addiction. Neuron, 59(1), 11–34.
Cesselin, F. (1995) Opioid and anti-opioid peptides. Fundamental & Clinical Pharmacology, 9(5):409-433.
Elhabazi, K., Trigo, J.M., Mollereau, C., Moulédous, L., Zajac, J.M., Bihel, F., Schmitt, M., Bourguignon, J.J., Meziane, H., Petit-demoulière, B., Bockel, F., Maldonado, R., Simonin, F. (2012) Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments. British Journal of Pharmacology, 165(2):424-435.
Heinricher, M.M., Tavares, I., Leith, J.L., Lumb, B.M. Descending control of nociception: Specificity, recruitment and plasticity. (2009) Brain Research Review. 60(1):214-225.
Toll, L., Bruchas, M. R., Calo’, G., Cox, B. M., & Zaveri, N. T. (2016). Nociceptin/Orphanin FQ Receptor Structure, Signaling, Ligands, Functions, and Interactions with Opioid Systems. Pharmacological Reviews, 68(2), 419–457.
Ueda, H. (2004). Locus-specific involvement of anti-opioid systems in morphine tolerance and dependence. Annals of the NY Academy of Science, 1025:376-382.
Kirkpatrick, D. R., McEntire, D. M., Hambsch, Z. J., Kerfeld, M. J., Smith, T. A., Reisbig, M. D., … Agrawal, D. K. (2015). Therapeutic Basis of Clinical Pain Modulation. Clinical and Translational Science, 8(6), 848–856.
Rivat, C., & Ballantyne, J. (2016). The dark side of opioids in pain management: basic science explains clinical observation. Pain Reports, 1(2), e570
Kosten, T. R., & George, T. P. (2002). The Neurobiology of Opioid Dependence: Implications for Treatment. Science & Practice Perspectives, 1(1), 13–20.