Case Reviews in Pain| Volume 12, ISSUE 10, P1025-1031, October 2011

Understanding and Treating Opioid Addiction in a Patient With Cancer Pain

      Mr. D. is a 25-year-old male who has struggled with heroin addiction since his late teens. He had initially completed a 30-day rehabilitation program but relapsed immediately and entered another 2-week program. It was during this hospitalization that laboratory abnormalities were noted, and he was subsequently diagnosed with acute myeloid leukemia. He received high-dose induction chemotherapy with cytarabine and daunorubicin but did not achieve remission. He was reinduced, achieved remission, and subsequently underwent stem cell transplantation with his younger sister as a donor. Throughout this prolonged 8-week hospitalization and treatment, he suffered from severe mucositis as well as abdominal pain of unclear etiology requiring patient controlled analgesia (PCA), delivering, at 1 point, over 600 mg of hydromorphone in a 24-hour period. By the time of discharge, the mucositis had resolved, the opioid gradually titrated downward, and he was transitioned to a 100-mcg fentanyl patch, which was weaned down as an outpatient over a 2-week period. Two weeks after titration off of fentanyl, the patient reported agitation, sweats, and nausea that continued. Mr. D’s parents accompanied him to each appointment; the patient continued to live with his parents so they could closely monitor him and they dispensed his medications due to the history of drug abuse. Less than 6 months from his transplant, his parents discovered evidence of an attempted transaction to purchase heroin, and the patient subsequently admitted to continued heroin use throughout his treatment including during his hospitalization. He continues to struggle with addiction; more than 300 days past transplant, he is currently at an inpatient drug rehab facility.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Alford D.P.
        • Compton P.
        • Samet J.H.
        • Alford D.P.
        • Compton P.
        • Samet J.H.
        Acute pain management for patients receiving maintenance methadone or buprenorphine therapy.
        Ann Internal Med. 2006; 144: 127-134
        • Bassareo V.
        • Musio P.
        • Di Chiara G.
        Reciprocal responsiveness of nucleus accumbens shell and core dopamine to food- and drug-conditioned stimuli.
        Psychopharmacology (Berl). 2010; 214: 687-697
        • Botelho M.F.
        • Relvas J.S.
        • Abrantes M.
        • Cunha M.J.
        • Marques T.R.
        • Rovira E.
        • Fontes Ribeiro C.A.
        • Macedo T.
        Brain blood flow SPET imaging in heroin abusers.
        Ann NY Acad Sci. 2006; 1074: 466-477
        • Carlezon Jr., W.A.
        • Thomas M.J.
        • Carlezon Jr., W.A.
        • Thomas M.J.
        Biological substrates of reward and aversion: A nucleus accumbens activity hypothesis.
        Neuropharmacology. 2009; 56: 122-132
        • Clapp P.
        • Bhave S.V.
        • Hoffman P.L.
        How Adaptation of the Brain to Alcohol Leads to Dependence: A Pharmacological Perspective.
        Alcohol Res Health. 2008; 31: 310-339
        • Colliver J.D.
        • Kopstein A.N.
        Trends in cocaine abuse reflected in emergency room episodes reported to DAWN. Drug Abuse Warning Network.
        Public Health Reports. 1991; 106: 59-68
        • Daglish M.R.
        • Weinstein A.
        • Malizia A.L.
        • Wilson S.
        • Melichar J.K.
        • Britten S.
        • Brewer C.
        • Lingford-Hughes A.
        • Myles J.S.
        • Grasby P.
        • Nutt D.J.
        Changes in regional cerebral blood flow elicited by craving memories in abstinent opiate-dependent subjects.
        Am J Psychiatry. 2001; 158: 1680-1686
        • Everitt B.J.
        • Robbins T.W.
        Neural systems of reinforcement for drug addiction: From actions to habits to compulsion.
        Nature Neurosci. 2005; 8: 1481-1489
        • Everitt B.J.
        • Belin D.
        • Economidou D.
        • Pelloux Y.
        • Dalley J.W.
        • Robbins T.W.
        Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction.
        Philos Trans R Soc Lond B Biol Sci. 2008; 363: 3125-3135
        • Forman S.D.
        • Dougherty G.G.
        • Casey B.J.
        • Siegle G.J.
        • Braver T.S.
        • Barch D.M.
        • Stenger V.A.
        • Wick-Hull C.
        • Pisarov L.A.
        • Lorensen E.
        Opiate addicts lack error-dependent activation of rostral anterior cingulate.
        Biol Psychiatry. 2004; 55: 531-537
        • Fuentealba J.A.
        • Forray M.I.
        • Gysling K.
        Chronic morphine treatment and withdrawal increase extracellular levels of norepinephrine in the rat bed nucleus of the stria terminalis.
        J Neurochem. 2000; 75: 741-748
        • Gass J.T.
        • Olive M.F.
        Glutamatergic substrates of drug addiction and alcoholism.
        Biochem Pharmacol. 2008; 75: 218-265
        • Gfroerer J.
        • Brodsky M.
        The incidence of illicit drug use in the United States, 1962–1989.
        Brit J Addiction. 1992; 87: 1345-1351
        • Goldstein R.Z.
        • Volkow N.D.
        Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortex.
        Am J Psychiatry. 2002; 159: 1642-1652
        • Goldstein R.Z.
        • Craig A.D.
        • Bechara A.
        • Garavan H.
        • Childress A.R.
        • Paulus M.P.
        • Volkow N.D.
        The neurocircuitry of impaired insight in drug addiction.
        Trends in Cogn Sci. 2009; 13: 372-380
        • Gourlay D.L.
        • Heit H.A.
        Pain and addiction: Managing risk through comprehensive care.
        J Addict Dis. 2008; 27: 23-30
        • Gourlay D.L.
        • Heit H.A.
        • Almahrezi A.
        Universal precautions in pain medicine: A rational approach to the treatment of chronic pain.
        Pain Med. 2005; 6: 107-112
        • Hyman S.E.
        Addiction: A disease of learning and memory.
        Am J Psychiatry. 2005; 162: 1414-1422
        • Hyman S.E.
        • Malenka R.C.
        • Nestler E.J.
        Neural mechanisms of addiction: The role of reward-related learning and memory.
        Ann Rev Neurosci. 2006; 29: 565-598
        • Kalivas P.W.
        • Volkow N.D.
        The neural basis of addiction: A pathology of motivation and choice.
        Am J Psychiatry. 2005; 162: 1403-1413
        • Kalivas P.W.
        • O’Brien C.
        Drug addiction as a pathology of staged neuroplasticity.
        Neuropsychopharmacology. 2008; 33: 166-180
        • Katz N.P.
        • Birnbaum H.G.
        • Castor A.
        Volume of prescription opioids used nonmedically in the United States.
        J Pain Palliat Care Pharmacother. 2010; 24: 141-144
        • Kirsh K.L.
        • Passik S.D.
        Palliative care of the terminally ill drug addict.
        Cancer Invest. 2006; 24: 425-431
        • Koob G.
        • Kreek M.J.
        Stress, dysregulation of drug reward pathways, and the transition to drug dependence.
        Am J Psychiatry. 2007; 164: 1149-1159
        • Koob G.F.
        • Le Moal M.
        Drug abuse: Hedonic homeostatic dysregulation.
        Science. 1997; 278: 52-58
        • Koob G.F.
        • Nestler E.J.
        The neurobiology of drug addiction.
        J Neuropsychiatry Clin Neurosci. 1997; 9: 482-497
        • Koob G.F.
        • Le Moal M.
        Drug addiction, dysregulation of reward, and allostasis.
        Neuropsychopharmacology. 2001; 24: 97-129
        • Koob G.F.
        A role for brain stress systems in addiction.
        Neuron. 2008; 59: 11-34
        • Koob G.F.
        Brain stress systems in the amygdala and addiction.
        Brain Res. 2009; 1293: 61-75
        • Koob G.F.
        • Simon E.J.
        The neurobiology of addiction: Where we have been and where we are going.
        J Drug Issues. 2009; 39: 115-132
        • Koob G.F.
        The role of CRF and CRF-related peptides in the dark side of addiction.
        Brain Res. 2010; 1314: 3-14
        • Koob G.F.
        • Volkow N.D.
        Neurocircuitry of addiction.
        Neuropsychopharmacology. 2010; 35: 217-238
        • Kreek M.J.
        Opiate and cocaine addictions: Challenge for pharmacotherapies.
        Pharmacol Biochem Behav. 1997; 57: 551-569
        • Kreek M.J.
        • Koob G.F.
        Drug dependence: Stress and dysregulation of brain reward pathways.
        Drug Alcohol Depend. 1998; 51: 23-47
      1. Kreek MJ: Neuropsychopharmacology: The Fifth Generation of Progress: An Official Publication of the American College of Neuropsychopharmacology 1491-1505, 2002

        • LaLumiere R.T.
        • Kalivas P.W.
        Glutamate release in the nucleus accumbens core is necessary for heroin seeking.
        J Neurosci. 2008; 28: 3170-3177
        • Le Moal M.
        • Koob G.F.
        Drug addiction: Pathways to the disease and pathophysiological perspectives.
        Eur Neuropsychopharmacol. 2007; 17: 377-393
        • Leshner A.I.
        Addiction is a brain disease, and it matters.
        Science. 1997; 278: 45-47
        • Martin W.R.
        • Fraser H.F.
        A comparative study of physiological and subjective effects of heroin and morphine administered intravenously in postaddicts.
        J Pharmaco Exp Ther. 1961; 133: 388-399
        • McClernon F.J.
        • Kozink R.V.
        • Lutz A.M.
        • Rose J.E.
        24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum.
        Psychopharmacology (Berl). 2009; 204: 25-35
        • McFarland K.
        • Lapish C.C.
        • Kalivas P.W.
        Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior.
        J Neurosci. 2003; 23: 3531-3537
        • McLellan A.T.
        • Lewis D.C.
        • O’Brien C.P.
        • Kleber H.D.
        Drug dependence, a chronic medical illness: Implications for treatment, insurance, and outcomes evaluation.
        JAMA. 2000; 284: 1689-1695
        • Passik S.D.
        • Kirsh K.L.
        • Casper D.
        Addiction-related assessment tools and pain management: Instruments for screening, treatment planning, and monitoring compliance.
        Pain Medicine. 2008; 9: S145-S166
        • Passik S.D.
        • Kirsh K.L.
        The interface between pain and drug abuse and the evolution of strategies to optimize pain management while minimizing drug abuse.
        Exp Clin Psychopharmacol. 2008; 16: 400-404
        • Regier D.A.
        • Myers J.K.
        • Kramer M.
        • Robins L.N.
        • Blazer D.G.
        • Hough R.L.
        • Eaton W.W.
        • Locke B.Z.
        The NIMH Epidemiologic Catchment Area program. Historical context, major objectives, and study population characteristics.
        Arch Gen Psychiatry. 1984; 41: 934-941
        • Robinson T.E.
        • Berridge K.C.
        Review. The incentive sensitization theory of addiction: Some current issues.
        Philos Trans R Soc Lond B Biol Sci. 2008; 363: 3137-3146
        • Rogers P.D.
        • Copley L.
        The nonmedical use of prescription drugs by adolescents.
        Adolesc Med. 2009; 20: 1-8
        • Ross S.
        • Peselow E.
        The neurobiology of addictive disorders.
        Clin Neuropharmacol. 2009; 32: 269-276
        • Savage S.R.
        • Joranson D.E.
        • Covington E.C.
        • Schnoll S.H.
        • Heit H.A.
        • Gilson A.M.
        Definitions related to the medical use of opioids: Evolution towards universal agreement.
        J Pain Symptom Manage. 2003; 26: 655-667
        • Shaham Y.
        • Erb S.
        • Leung S.
        • Buczek Y.
        • Stewart J.
        CP-154,526, a selective, non-peptide antagonist of the corticotropin-releasing factor1 receptor attenuates stress-induced relapse to drug seeking in cocaine- and heroin-trained rats.
        Psychopharmacology (Berl). 1998; 137: 184-190
        • Shalev U.
        • Finnie P.S.
        • Quinn T.
        • Tobin S.
        • Wahi P.
        A role for corticotropin-releasing factor, but not corticosterone, in acute food-deprivation-induced reinstatement of heroin seeking in rats.
        Psychopharmacology (Berl). 2006; 187: 376-384
        • Smith S.M.
        • Vale W.W.
        The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress.
        Dialog Clin Neurosci. 2006; 8: 383-395
        • Tenore P.L.
        Advanced urine toxicology testing.
        J Addict Dis. 2010; 29: 436-448
        • Volkow N.D.
        • Fowler J.S.
        • Wang G.J.
        • Hitzemann R.
        • Logan J.
        • Schlyer D.J.
        • Dewey S.L.
        • Wolf A.P.
        Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers.
        Synapse. 1993; 14: 169-177
        • Volkow N.D.
        • Chang L.
        • Wang G.J.
        • Fowler J.S.
        • Ding Y.S.
        • Sedler M.
        • Logan J.
        • Franceschi D.
        • Gatley J.
        • Hitzemann R.
        • Gifford A.
        • Wong C.
        • Pappas N.
        Low level of brain dopamine D2 receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex.
        Am J Psychiatry. 2001; 158: 2015-2021
        • Volkow N.D.
        • Fowler J.S.
        • Wang G.J.
        • Swanson J.M.
        Dopamine in drug abuse and addiction: Results from imaging studies and treatment implications.
        Mol Psychiatry. 2004; 9: 557-569
        • Volkow N.D.
        • Wang G.J.
        • Fowler J.S.
        • Tomasi D.
        • Telang F.
        • Baler R.
        Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain’s control circuit.
        Bioessays. 2010; 32: 748-755
        • Wang G.J.
        • Volkow N.D.
        • Fowler J.S.
        • Logan J.
        • Abumrad N.N.
        • Hitzemann R.J.
        • Pappas N.S.
        • Pascani K.
        Dopamine D2 receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal.
        Neuropsychopharmacology. 1997; 16: 174-182
        • Watanabe T.
        • Nakagawa T.
        • Yamamoto R.
        • Maeda A.
        • Minami M.
        • Satoh M.
        Involvement of noradrenergic system within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats.
        Psychopharmacology. 2003; 170: 80-88
        • Wise R.A.
        Dopamine, learning and motivation.
        Nat Rev Neurosci. 2004; 5: 483-494
        • Zhou W.
        • Kalivas P.W.
        N-acetylcysteine reduces extinction responding and induces enduring reductions in cue- and heroin-induced drug-seeking.
        Biol Psychiatry. 2008; 63: 338-340
        • Zorrilla E.P.
        • Koob G.F.
        Progress in corticotropin-releasing factor-1 antagonist development.
        Drug Discovery Today. 2010; 15: 371-383