Opioids II pp 803-823 | Cite as

Opioid Addiction

  • C. P. O’Brien
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 104 / 2)


That the endogenous opioid system is likely to be involved in the clinical syndrome of opiate addiction is self-evident. Yet research efforts over more than 15 years have failed to find a clear link between addiction and endogenous opioids. The complexity of the opioid system and the difficulty in measuring its level of activity have made studies in human subjects difficult to perform and to interpret. Another important barrier has been the variability of the clinical syndrome of addiction. This variability hinders the gathering of a group of homogeneous patients for the purpose of measuring biological correlates of addiction. Of course, addiction is not simply a biological phenomenon. It is a complex of bio-psycho-social factors influenced strongly by environmental variables and previous experiences.


Methadone Maintenance Endogenous Opioid Opiate Receptor Heroin Addict Opiate Withdrawal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aghajanian GK (1978) Tolerance of locus coeruleus neurons to morphine and suppression of withdrawal response by clonidine. Nature 276:186–187PubMedCrossRefGoogle Scholar
  2. AP ACNS: American Psychiatric Association Committee on Nomenclature and Statistics (1987) Diagnostic and statistical manual of mental disorders, 3rd edn. American Psychiatric Association, WashingtonGoogle Scholar
  3. Auriacombe M, Tignol J, LeMoal M, Stinus L (1990) Transcutaneous electrical stimulation with Limoge current potentiates morphine analgesia and attenuates opiate abstinence syndrome. Biol Psychiatry 28:650–656PubMedCrossRefGoogle Scholar
  4. Bergström L, Terenius L (1979) Enkephalin levels decrease in rat striatum during morphine abstinence. Eur J Parmacol 60:349–352CrossRefGoogle Scholar
  5. Berman RF, Lee JA, Olson KL, Goldman MS (1984) Effects of naloxone on ethanol dependence in rats. Drug Alcohol Depend 13:245–254PubMedCrossRefGoogle Scholar
  6. Bickel WK, Stitzer ML, Bigelow GE, Liebson IA, Jasinski DR, Johnson RE (1988) A clinical trial of buprenorphine: comparison with methadone in the detoxification of heroin addicts. Clin Pharmacol Ther 43:72–78PubMedCrossRefGoogle Scholar
  7. Blum K, Wallace JE, Eubanks J, Schwertner HA (1975) Effects of naloxone on ethanol withdrawal, preference and narcosis. Pharmacologist 17:197Google Scholar
  8. Blum K, Futterman S, Wallace JE, Schwertner HA (1977) Naloxone-induced inhibition of ethanol dependence in mice. Nature 265:49–51PubMedCrossRefGoogle Scholar
  9. Charness ME, Gordon AS, Diamond I (1983) Ethanol modulation of opiate receptors in cultured neuronal cells. Science 222:1146–1148CrossRefGoogle Scholar
  10. Christie MJ, Chesher GB (1982) Physical dependence on physiologically released endogenous opiates. Life Sci 30:1173–1177PubMedCrossRefGoogle Scholar
  11. Christie MJ, Chester GB, Bird K (1984) No evidence for a protracted change in endogenous opioid activity following chronic opiate treatment in mice: parallel recovery of cross tolerance to stress and morphine anticieption. Psychopharmacology 82:378–381CrossRefGoogle Scholar
  12. Clement-Jones V, Lowry PJ, McLoughlin L, Besser GM, Rees LH, Wen HL (1979) Acupuncture in heroin addicts: changes in met-enkephalin and β-endorphin in blood and cerebrospinal fluid. Lancet 2:380–383PubMedCrossRefGoogle Scholar
  13. Cornish J, Henson D, Levine S, Volpicelli J, Inturrisi CE, Yoburn BC, O’Brien CP (1992) Morphine sensitivity in normal subjects after naltrexone treatment. Am J Addiction (in press)Google Scholar
  14. Cushman D, Morris D, Adams M, Dewey W (1981) Opiate addiction and plasma beta-endorphin-like immunoreactivity: methadone maintained, recently detoxified and early naltrexone treated ex-addicts. Alcohol Drug Res 7(5–6):533–540Google Scholar
  15. DeWitte P (1984) Naloxone reduces alcohol intake in a free-choice procedure even when both drinking bottles contain saccharin sodium or quinine substances. Neuropsychobiology 12:73–77CrossRefGoogle Scholar
  16. Dole VP, Nyswander M (1967) Heroin-addiction - a metabolic disease. Arch Intern Med 120:19–24PubMedCrossRefGoogle Scholar
  17. Ellison F, Ellison W, Daulouéde JP (1987) Opiate withdrawal and electro-stimulation double-blind experiments. Encéphale 13:225–229PubMedGoogle Scholar
  18. Emrich HM, Nusselt L, Gramsch John S (1983) Heroin addiction: beta-endorphin immunoactivity in plasma increases during withdrawal. Pharmacophsychiat 16:93–96CrossRefGoogle Scholar
  19. Facchinetti F, Grasso A, Petraglia F, Parrini D, Volpe A, Genazzani AR (1984) Impaired circadian rhythmicity of beta-lipotrophin, beta-endorphin and ACTH in heroin addicts. Acta Endocrinol (Copenh). 105(2):149–55Google Scholar
  20. Fratta W, Yany HYT, Hong J, Costa E (1977) Stability of metenkephalin content in brain structures of morphine dependent or foot-shock stresed rats. Nature 268:452PubMedCrossRefGoogle Scholar
  21. Frischknecht HR, Siegfried B, Waser PG (1988) Opiods and behavior, genetic aspects. Experientia 44:473–481PubMedCrossRefGoogle Scholar
  22. Gold MS, Redmond DE, Kleber HD (1979) Noradrenergic hyperactivity in opiate withdrawal supported by clonidine reversal of opiate withdrawal. Am J Psychiatry 136: 100–102PubMedGoogle Scholar
  23. Gold MS, Pottash ALC, Extein IRL, Martin DA, Finn L, Sweeney D, Kleber H (1981) Evidence for an endorphin dysfunction in methadone addicts: lack of ACTH response to naloxone. Drug Alcohol Depend 8:257–262PubMedCrossRefGoogle Scholar
  24. Herz A, Höllt V, Przewlocki R (1980) Endogenous opioids and addiction. Brain and pituitary peptides ferring symposium. Karger, Baser: pp 183–189Google Scholar
  25. Hiller JM, Angle LM, Simon EJ (1981) Multiple opiate receptors: alcohol selectively inhibits binding to delta receptors. Science 214:468–469PubMedCrossRefGoogle Scholar
  26. Ho AK, Ho CC (1979) Toxic interactions of ethanol with other central depressants: antagonism by naloxone to narcosis and lethality. Pharmacol Biochem Behav 11:111–114PubMedCrossRefGoogle Scholar
  27. Ho WKK, Wen HL, Ling N (1980) Beta-endorphin-like immunoactivity in the plasma of heroin addicts and normal subjects. Neuropharmacol 19:117–120CrossRefGoogle Scholar
  28. Hoffman L, Burges WP, Wilson G, Montgomery J (1989) Low plasma beta-endorphin in post-traumatic stress disorder. Aust NZ J Psychiatry 2:269–273CrossRefGoogle Scholar
  29. Holmstrand J, Gunne L-M, Wahlstrom A, Terenius L (1981) CSF-endorphins in heroin addicts during methadone maintenance and during withdrawal. Pharmacopsychiatria 14: 126–128PubMedCrossRefGoogle Scholar
  30. Hosobuchi Y, Rossier J, Bloom FE, Guillemin R (1979) Stimulation of human periaqueductal gray for pain relief increases immunoreactive β-endorphin in ventricular fluid. Science 203:279–281PubMedCrossRefGoogle Scholar
  31. Hubbell CL, Czirr SA, Hunter GA, Beaman CM, LeCann NC, Reid LD (1986) Consumption of ethanol solution is potentiated by morphine and attenuated by naloxone persistently across repeated daily administrations. Alcohol 3:39–54PubMedCrossRefGoogle Scholar
  32. Hubbell CL, Czirr SA, Reid LD (1987) Persistence and specificity of small doses of morphine on intake of alcoholic beverages. Alcohol 4:149–156PubMedCrossRefGoogle Scholar
  33. Kiser RS, Gatchel RJ, Bhatia K, Khatami M, Huang X-Y, Altshuler KZ (1983) Acupuncture relief of chronic pain syndrome correlates with increased plasma met-enkephalin concentrations. Lancet 2:1394PubMedCrossRefGoogle Scholar
  34. Kosten TR, Kreek MJ, Raguneth J, Kleber HD (1986) A preliminary study of beta endorphin during chronic naltrexone maintenance treatment in ex-opiate addicts. Life Sci 39:55–59PubMedCrossRefGoogle Scholar
  35. Kosten TR, Kreek MJ, Swift C, Carney MK, Ferdinands L (1987) Beta-endorphin levels in CSF during methadone maintenance. Life Sci 41:271–278CrossRefGoogle Scholar
  36. Kreek MJ, Wardlaw SL, Hartman N, Raghunath J, Friedman J, Schneider B, Frantz AG (1983) Circadian rhythms and levels of beta-endorphin, ACTH, and cortisol during chronic methadone maintenance treatment in humans. Life Sci 33:409–411PubMedCrossRefGoogle Scholar
  37. Ling W, Charuvastra VC, Kaim SC, Klett J (1976) Methadyl acetate and methadone as maintenance treatments, for heroin addicts. Arch Gen Psychiatry 33:709–720PubMedCrossRefGoogle Scholar
  38. Malfroy B, Schertz JP, Guyon A, Roques BP, Schwartz JC (1978) High affinity enkephalin degrading peptidase in brian is increased after morphine. Nature 276:523PubMedCrossRefGoogle Scholar
  39. Malin DH, Hempel RJ, Exley RJ, Addington S (1986) Clonidine reverses the behavioral and respiratory effects of continuous naloxone infusion. Pharmacol Biochem Behav 25:989–993PubMedCrossRefGoogle Scholar
  40. Malin DH, Murray JB, Crucian GP, Schweitzer FC, Cook RE, Skolnick MH (1988) Transcanial auricular electrostimulation: naloxone-reversible attenuation of pain sensitivity and opiate abstinence syndrome. Biol Psychiatry 24:886–890PubMedCrossRefGoogle Scholar
  41. Malizia E, Andreucci G, Paolucci D, Crescenzi A, Fabri F, Fraioli F (1979) Electroacupuncture and peripheral β-endorphin and ACTH levels. Lancet 2:535–536PubMedCrossRefGoogle Scholar
  42. Martin WR, Jasinski D (1969) Physiological parameters of morphine in mantolerance, early abstinence, protracted abstinence. J Psychiatr Res 7:9–16PubMedCrossRefGoogle Scholar
  43. Middaugh LD, Read E, Boggan W (1978) Effects of naloxone on ethanol induced alterations of locomotor activity in C57BL/6 mice. Pharmacol Biochem Behav 11:157–160CrossRefGoogle Scholar
  44. Morley JE, Levine AS (1980) Stress-induced eating is mediated through endogenous opiates. Science 209:1259–1261PubMedCrossRefGoogle Scholar
  45. Myer EC, Morris DL, Brase DA, Dewey WL, Zimmerman A W (1990) Naltrexone therapy of apnea in children with elevated cerebrospinal fluid beta-endorphin. Ann Neurol 27:75–80PubMedCrossRefGoogle Scholar
  46. Nyberg F, Wahlstrom A, Sjölund B, Terenius L (1983) Characterization of electrophoretically separable endorphins in human CSF. Brain Res 259:267–274PubMedCrossRefGoogle Scholar
  47. O’Brien CP (1978) Clinical pharmacology of narcotic antagonists. Ann NY Acad Sci 311:232–240PubMedCrossRefGoogle Scholar
  48. O’Brien CP, Terenius LY, Nyberg F, McLellan AT, Eriksson I (1988) Endogenous opioids in cerebrospinal fluid of opioid-dependent humans. Biol Psychiatry 24:649–662PubMedCrossRefGoogle Scholar
  49. O’Brien CP, Childress AR, McLellan AT, Ehrman R (1990) The use of cue exposure as an aid in the prevention of relapse to cocaine or heroin dependence. Addict Behav 15:355–365PubMedCrossRefGoogle Scholar
  50. O’Malley SS, Jaffe A, Chang G, Witte G, Schottenfeld RS, Rounsaville BJ (1991) Naltrexone in the treatment of alcohol dependence: preliminary findings. In: Naranjo CA, Sellers EM (eds) Novel pharmacological interventions for alcoholism. Springer, New York, Berlin Heidelberg, pp 148–157Google Scholar
  51. Orlowski JP (1982) Endorphins in infant apnea. N Engl J Med 307:186–187PubMedGoogle Scholar
  52. Pert CB, Snyder SN (1976) Opiate receptor: demonstration in nervous tissue. Science 179:1011–1014CrossRefGoogle Scholar
  53. Pitman RK, van der Kolk BA, Orr SP, Greenberg MS (1990) Naloxone-reversible analgesic response to combat-related stimuli in post-traumatic stress disorder. Arch Gen Psychiatry 47:541–544PubMedCrossRefGoogle Scholar
  54. Reid LD, Hunter GA (1984) Morphine and naloxone modulate intake of ethanol. Alcohol 1:33–37PubMedCrossRefGoogle Scholar
  55. Reynolds DV (1969) Surgery in the rat during electrical anesthesia induced by focal brain stimulation. Science 164:444–445PubMedCrossRefGoogle Scholar
  56. Samson HH, Doyle TF (1985) Oral ethanol self-administration in the rat: effect of naloxone. Pharmacol Biochem Behavior 22:91–99CrossRefGoogle Scholar
  57. Schulz R, Wiister M, Herz A (1979) Supersensitivity to opioids following chronic blockade of endorphin activity by naloxone. Naunyn Schmiedebergs Arch Pharmacol 306:93–96PubMedCrossRefGoogle Scholar
  58. Sjölund B, Terenius L, Eriksson M (1977) Increased cerebrospinal fluid levels in endorphins after electro-acupuncture. Acta Physiol Scand 100:382–384PubMedCrossRefGoogle Scholar
  59. Su CY, Lin CS, Peng C, Cheng CS, Loh HH, Li CH, Way EL (1980) Suppression of morphine abstinence in heroin addicts by β-endorphin. In: Costa E, Trabucchi M (eds) Neural peptides and neuronal communication. Raven Press, New York, pp 503–509Google Scholar
  60. Tamsen A, Hartvig P, Dahlström B, Wahlström A, Terenius L (1980) Endorphins and on-demand pain relief. Lancet 2:769–770CrossRefGoogle Scholar
  61. Terenius L (1984) Opiate tolerance and dependence. Res Adv Alcohol 8:1–21Google Scholar
  62. Terenius L, Wahlstrom A (1975) Morphine-like ligand for opiate receptors in human CSF. Life Sci 16:1759–1764CrossRefGoogle Scholar
  63. Terenius L, Nyberg F (1988) Neuropeptide processing/converting/inactivating enzymes in human CSF. IntI Rev of Neurobiology 30:101–121CrossRefGoogle Scholar
  64. Volpicelli JR, Davis MA, Olgin JE (1986) Naltrexone blocks the post-shock increase of ethanol consumption. Life Sci 38:841–847PubMedCrossRefGoogle Scholar
  65. Volpicelli JR, O’Brien CP, Alterman AI, Hayashida M (1990) Naltrexone and the treatment of alcohol dependence: initial observations. In: Reid LB (ed) Opioids, bulimia, and alcohol abuse and alcoholism. Springer, Berlin Heidelberg New York, pp 195–214Google Scholar
  66. Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psy (in press)Google Scholar
  67. Wei ET (1981) Enkephalin analogs and physical dependence. J Pharmacol Exp Ther 1:12–18Google Scholar
  68. Wen HL, Ho WKK, Ling N, Mehal ZD, Ng YH (1980) Immunoassayable betaendorphin level in the plasma and CSF of heroin addicted and normal subjects before and after electro-acupuncture. Am J Chin Med 2:154–159Google Scholar
  69. Woody GE, Luborsky L, McLellan AT, O’Brien CP, Beck AT (1983) Psychotherapy for opiate addicts: does it help? Arch Gen Psychiatry 40:639–648PubMedCrossRefGoogle Scholar
  70. Yoburn BC, Goodman RR, Cohen AH, Pasternak GW, Inturrisi CE (1985) Increased analgesic potency of morphine and increased brain opioid binding sites in the rat following chronic naltrexone treatment. Life Sci 36:2325–2332PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • C. P. O’Brien

There are no affiliations available

Personalised recommendations