Opioids: Analgesia, Euphoria, Dysphoria, and Oblivion: Observations and a Hypothesis
Main Article Content
Abstract
Introduction: In a previous paper, we inquired into the root causes of the two opioid crises our nation is facing, one evolved from the effects of political and psychosocial forces, one manufactured by the Centers for Disease Control and Prevention. This inquiry led us to suspect that the very different opioid consumption patterns of various groups of people were driven by very different motivations related to the opioid experience. Here we explore four potential motivations or disincentives: analgesia, euphoria, dysphoria, and the search for oblivion. We particularly focus on two populations more likely to be motivated by the search for oblivion: people addicted to opioids and terminal cancer patients, and the problem of tolerance.
Methods: Analytic review of the scientific literature.
Results and Discussion: Essentially all patients managed in American clinics, including many patients with cancer, are motivated by a simple desire for analgesia. A search for euphoria almost certainly motivates the population of people who use mind-altering drugs, including opioids, for recreation. Dysphoria is a feeling of unpleasantness associated with a particular opioid sufficient to motivate a patient to refuse the drug. It represents a common challenge in managing patients in chronic pain. The search for oblivion appears to be the primary motivation for people with opioid addiction. It may also be a motivating factor in certain patients with terminal cancer who suffer not just pain but also agonizing existential crisis.
Conclusion: A greater appreciation on the part of clinicians, scientists and policy makers of the different factors that motivate use of opioids could have major implications for how we handle different people consuming opioids. It could disabuse us of the suspicion that every patient in pain is seeking euphoria rather than analgesia and help us to understand their vanishingly small risk of drug abuse or addiction. It could lead to serious study of the mechanisms of dysphoria and the development of means to circumvent it. It could lead to improved approaches to patients with pain from terminal cancer and optimal strategies for dealing with the addiction crisis in the streets.
Keywords:
opioids, analgesia, euphoria, dysphoria, oblivion, terminal cancer, opioid addiction
Article Details
How to Cite
NADEAU, Stephen E.; LAWHERN, Richard A..
Opioids: Analgesia, Euphoria, Dysphoria, and Oblivion: Observations and a Hypothesis.
Medical Research Archives, [S.l.], v. 12, n. 6, june 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5411>. Date accessed: 21 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i6.5411.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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31. Alexander BK, Beyerstein BL, Hadaway PF, Coambs RB. Effects of early and later colony housing on oral ingestion of morphine in rate. Pharmacol Biochem Behav. 1981;15(4):571-576.
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33. Robins LN. Vietnam veterans’ rapid recovery from heroin addiction: a fluke or a normal expectation? Addiction. 1993;88:1041-1054._Doi:10.1111/j.1360-0443.1993.tb02123.x
34. Robins LN, Helzer JE, Hesselbrock M. Vietnam veterans three years after Vietnam: how our study changed our view of heroin. American Journal of Addictions. 2010;19:203-211. Doi: 10.1111/j.1521-0391.2010.00046.x
35. Verghese A. The Covenant of Water. New York: Grove Press; 2023.
36. Roberts GD. Shantaram. New York: St. Martin’s Griffin; 2003.
37. Elkins C. What does heroin feel like? In. DrugRehab.com. https://www.drugrehab.com/addiction/drugs/heroin/what-heroin-feels-like/.
38. Okoye O. What does a heroin high feel like? In: Weiman E, ed. The Recovery Village. https://www.therecoveryvillage.com/heroin-addiction/heroin-high/.
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45. Rigg KK, Kusiak ES. Perceptions of fentanyl among African Americans who misuse opioids: implications for risk reduction. Harm Reduct J. 2023;20:179. Doi: 10.1016/j.drugpo.2017.06.004
46. Collin E, Poulain P, Gauvain-Piquard A, Petit G, Pichard-Leandri E. Is disease progression the major factor in morphine ‘tolerance’ in cancer pain treatment? Pain. 1993;55:319-326.
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49. Mercadante S. Refractory cncer pain and intrathecal therapy: critical review of a systematic review. Pain Ther. 2023;12:645-654. Doi:10.1007/s40122-023-00507-z
50. Staats PS, Yearwood T, Charapata S, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291(1):63-70. Doi:10.1001/jama.291.1.63
51. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain (Review). Cochr Database Syst Rev. 2016(4). Doi:10.1002/14651858.CD003868.pub4
52. Schug SA, Zech D, Grond S, Jung H, Meuser T, Stobbe B. A long-term survey of morphine in cancer pain patients. J Pain Symptom Manage. 1992;7(5):259-266.
53. Donner B, Zenz M, Strumpf M, Raber M. Long-term treatment of cancer pain with transdermal fentanyl. J Symptom Manage. 1998;15(3):168-175.
54. Hwang IC, Bruera E, Park SM. Use of intravenous fentanyl againat morphine tolerance in breakthrough pain: a case series and literature review. Am J Hospice Palliat Med. 2014;31(1). Doi:10.1177/1049909112474112
55. Griffin S, Cubanski J, Neuman T. Medicare and end-of-life care. JAMA. 2016;316(17):1754. Doi:10.1001/jama.2016.15577
56. Jawed A, Comer AR. Disparities in end-of-life care for racial minorities: a narrative review. Ann Palliative Med. 2024;13(2):309-321. Doi:10.21037/apm-23-459
2. Anderson EM, Tsvetkov E, Galante A, et al. Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner. PNAS. 2023;120(7):e2210953120. Doi:10.1073/pnas.2210953120
3. Dowell D, Haegerich T, Chou R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:1-49. Doi: 10.15585/mmwr.rr6501e1
4. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice gudeline for prescribing opioids for pain — Unitest States, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(3):1-95. Doi: 10.15585/mmwr.rr7103a1.
5. Nadeau SE, Lawhern RA. The two opioid crises. Problems, causes, and potential solutions: an analytic review. Med Res Arch. 2023;11(12). Doi:10.18103/mra.v 11i12.4846
6. Nadeau SE, Wu JK, Lawhern RA. Opioids and chronic pain: an analytic review of the clinical evidence. Front Pain Res. 2021;2(721357). Doi:10.3389/fpain.2021.721357
7. Brat GA, Agniel D, Beam A, et al. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study. BMJ. 2018;360:j5790.Doi:10.1136/bmj.j5790
8. Nadeau SE, DelRocco NJ, Wu SS. Opioid trials: Time for a new approach. Enriched enrollment randomized gradual withdrawal designs. Pain Manag. 2022;12(3):243-247.Doi: 10.2217/pmt-2021-0112
9. Melzack R. The trajedy of needless pain. Scientific American. 1990;262(2):27-33. Doi: 10.1038/scientificamerican0290-27
10. Milligan K, Lanteri-Minet M, Borchert K, et al. Evaluation of long-term efficacy and safety of transdermal fentanyl in the treatment of chronic noncancer pain. J Pain. 2001;2:197-204. Doi: 10.1054/jpai.2001.25352
11. Mystakidou K, Parpa E, Tsilika E, et al. Long-term management of noncancer pain with transdermal therapeutic system-fentanyl. J Pain. 2003;4:298-306. Doi: 10.1016/s1526-5900(03)00632-1
12. Portenoy RK, Farrar JT, Backonja M-M, et al. Long-term use of controlled-release oxycodone for noncancer pain: results of a 3-year registry study. Clin J Pain. 2007;23:287-299. Doi: 10.1097/AJP.0b013e31802b582f.
13. Roth SH, Fleischmann RM, Burch FX, et al. Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain. Arch Int Med. 2000;160:853-860. Doi: 10.1001/archinte.160.6.853
14. Kiernan TE. A Treasury of Albert Schweitzer. Open Road Media; 2014.
15. Institute of Medicine. Relieving Pain in America. A Blueprint for Transforming Prevention, Care, Education, and Research. In. Washington, D.C.: The National Academies Press; 2011. https://nap.nationalacademies.org/catalog/13172/relieving-pain-in-america-a-blueprint-for-transforming-prevention-care
16. Moore RA, Derry S, Taylor RS, Straube S, Phillips CJ. The costs and consequences of adequately managed chronic non-cancer pain and chronic neuropathic pain. Pain Pract. 2014;14:79-94. Doi: 10.1111/papr.12050
17. Nadeau SE, Lawhern RA. Management of chronic non-cancer pain: a framework. Pain Manag. 2022;ePub(6):751-777. Doi:10.2217/pmt-2022-0017
18. Ochoa LA, Naeem F, White AJ, Bijur PE, Friedman BW. Opioid-induced euphoria among emergency department patients with acute severe pain: An analysis of data from a randomized trial. Acad Emerg Med. 2020;27:1100-1105. Doi:10.1111/acem.13946
19. Friedman BW, Latev A, Campbell C, White D. Opioid-induced “likeability” and “feeling good” are not associated with return visits to an ED among migraine patients administered IV hydromorphone. Headache. 2018;58:750-754. Doi: 10.1111/head.13292
20. Hart CL. Drug Use for Grown-Ups. New York: Penguin Press; 2021.
21. Agarwal D, Udoji MA, Trescot A. Genetic testing for opioid pain management. Pain Ther. 2017;6:93-105. Doi: 10.1007/s40122-017-0069-2
22. Obeng AO, Hamadeh I, Smith M. Review of opioid pharmacogenetics and considerations for pain management. Pharmacotherapy. 2017;27:1105-1121. doi: 10.1002/phar.1986
23. Emery MA, Eitam S. Members of the same opioid family are not alike; different opioids, different consequences, hope for the opioid crisis? Prog Neuropsychopharmacol Biol Psychiatry. 2019;92:428-449. Doi:10.1007/s40122-017-0069-2
24. Galvan A, Skorpen F, Klepstad P, et al. Multiple loci modulate opioid therapy response for cancer pain. Clin Cancer Res. 2011;17:4581-4597. Doi:10.1158/1078-0432.CCR-10-3028
25. Trescot AM, Faynboym S. A review of the role of genetic testing in pain medicine. Pain Phys. 2014;17(5):425-445.
26. Cherny N, Ripamonti C, Pereira J, et al. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol. 2001;19:2542-2554.
27. Quang-Cantagrel N, Wallace MS, Magnuson SK. Opioid substitution to improve the effectiveness of chronic noncancer pain control: a chart review. Anesth Analg. 2000;90:933-937. Doi:10.1213/00000539-200004000-00029
28. Rosengarten OS, Lamed Y, Zisling T, Feigin A, Jacobs JM. Palliative sedation at home. J Palliat Care. 2009;25(1):5-11.
29. Morita T. Palliative sedation to relieve psycho-existential suffering of terminally ill cancer patients. J Pain Symptom Manag. 2004;28(5):445-450. Doi: 10.1016/j.jpainsymman.2004.02.017
30. Tan F, Li N, Wu Y, Zhang C. Palliative sedation determinants: systematic review and meta-analysis in palliative medicine. BMJ Supp Pall Care. 2023;13:e664-e675. Doi: 10.1136/spcare-2022-004085
31. Alexander BK, Beyerstein BL, Hadaway PF, Coambs RB. Effects of early and later colony housing on oral ingestion of morphine in rate. Pharmacol Biochem Behav. 1981;15(4):571-576.
32. Raz S, Berger BD. Social isolation increases morphine intake: behavioral and psychopharmacological aspects. Behav Pharmacol. 2010;21:39-46. Doi: 10.1097/FBP.0b013e32833470bd
33. Robins LN. Vietnam veterans’ rapid recovery from heroin addiction: a fluke or a normal expectation? Addiction. 1993;88:1041-1054._Doi:10.1111/j.1360-0443.1993.tb02123.x
34. Robins LN, Helzer JE, Hesselbrock M. Vietnam veterans three years after Vietnam: how our study changed our view of heroin. American Journal of Addictions. 2010;19:203-211. Doi: 10.1111/j.1521-0391.2010.00046.x
35. Verghese A. The Covenant of Water. New York: Grove Press; 2023.
36. Roberts GD. Shantaram. New York: St. Martin’s Griffin; 2003.
37. Elkins C. What does heroin feel like? In. DrugRehab.com. https://www.drugrehab.com/addiction/drugs/heroin/what-heroin-feels-like/.
38. Okoye O. What does a heroin high feel like? In: Weiman E, ed. The Recovery Village. https://www.therecoveryvillage.com/heroin-addiction/heroin-high/.
39. Peri C. Heroin. In: Casarella J, ed. WebMD. https://www.webmd.com/mental-health/addiction/heroin-use.
40. Swaim E. Everything you need to know about heroin. In: Peckham A, ed. Healthline. https://www.healthline.com/health/substance-use/what-is-heroin.
41. Hampton D. Heroin addiction and abuse. In. AddictionCenter. https://www.addictioncenter.com/drugs/heroin/.
42. Martinez S, Brandt L, Comer SD, Levin FR, Jones JD. The subjective experience of heroin effects among individuals with chronic opioid use: Revisiting reinforcement in an exploratory study. Addict Neurosci. 2022;4. Doi: 10.1016/j.addicn.2022.100034
43. Nolte K, Drew AL, Friedmann PD, Romo E, Kinney LM, Stopka TJ. Opioid initiation and injection transition in rural northern New England: A mixed-methods approach. Drug Alcohol Dep. 2020;217:108256. Doi: 10.1016/j.drugalcdep.2020.108256
44. Ciccarone D, Ondocsin J, Mars SG. Heroin uncertainties: Exploring users’ perceptions of fentanyl-adulterated and -substituted ‘heroin’. Int J Drug Policy. 2017;46:146-155.
45. Rigg KK, Kusiak ES. Perceptions of fentanyl among African Americans who misuse opioids: implications for risk reduction. Harm Reduct J. 2023;20:179. Doi: 10.1016/j.drugpo.2017.06.004
46. Collin E, Poulain P, Gauvain-Piquard A, Petit G, Pichard-Leandri E. Is disease progression the major factor in morphine ‘tolerance’ in cancer pain treatment? Pain. 1993;55:319-326.
47. Kesten JM, Holder E, Ayres R, et al. Changes in the development of opioid tolerance on re-exposure among people who use heroin: A qualitative study. PLoS ONE. 2022;17(6):e0269379. Doi:10.1371/journal.pone.0269379
48. Huang Y-F, Kuo H-S, Lew-Ting C-Y, et al. Mortality among a cohort of drug users after their release from prison: an evaluation of the effectiveness of a harm reduction program in Taiwan. Addiction. 2011;106:1437-1445. Doi:10.1111/j.1360-0443.2011.03443.x
49. Mercadante S. Refractory cncer pain and intrathecal therapy: critical review of a systematic review. Pain Ther. 2023;12:645-654. Doi:10.1007/s40122-023-00507-z
50. Staats PS, Yearwood T, Charapata S, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291(1):63-70. Doi:10.1001/jama.291.1.63
51. Wiffen PJ, Wee B, Moore RA. Oral morphine for cancer pain (Review). Cochr Database Syst Rev. 2016(4). Doi:10.1002/14651858.CD003868.pub4
52. Schug SA, Zech D, Grond S, Jung H, Meuser T, Stobbe B. A long-term survey of morphine in cancer pain patients. J Pain Symptom Manage. 1992;7(5):259-266.
53. Donner B, Zenz M, Strumpf M, Raber M. Long-term treatment of cancer pain with transdermal fentanyl. J Symptom Manage. 1998;15(3):168-175.
54. Hwang IC, Bruera E, Park SM. Use of intravenous fentanyl againat morphine tolerance in breakthrough pain: a case series and literature review. Am J Hospice Palliat Med. 2014;31(1). Doi:10.1177/1049909112474112
55. Griffin S, Cubanski J, Neuman T. Medicare and end-of-life care. JAMA. 2016;316(17):1754. Doi:10.1001/jama.2016.15577
56. Jawed A, Comer AR. Disparities in end-of-life care for racial minorities: a narrative review. Ann Palliative Med. 2024;13(2):309-321. Doi:10.21037/apm-23-459