Abstract
The central role of the opioid system and its multiple connections to other neurotransmitter and neuroendocrine systems favours its involvement in many physiological functions and behaviours and, as a consequence, in many disorders, including psychiatric disorders. In addition to substance abuse or addiction, the efficacy of opioid receptor antagonist (ORA) treatment has been assessed in various disorders such as eating disorders, schizophrenia, self-injurious behaviour, autism, tics, obsessive-compulsive disorders and trichotillomania, and post-traumaticstress disorder, as opioids may play an important or prominent role in the pathophysiology of these disorders. Although the efficacy of ORA treatment remains controversial for most of these pathologies, the data are encouraging and an improvement of symptoms was mostly found when long-acting ORAs were used, given for several weeks and used as adjuncts to more classical medications. Moreover, in most of these pathologies, ORAs seemed to act by reducing the intensity and frequency of a specific pathological behaviour, which can be characterised as compulsive, repetitive, stereotyped and ‘uncontrollable’, and which can be linked to a reward-seeking or an addictive dimension.
Our global impression is that a dimensional approach would be of great value in investigating mental disorders, and of great help in defining the targets that can be expected to be reached by a specific medication. In this dimensional perspective opioid antagonists alone are not believed to have a decisive global therapeutic effect on any of the diseases reviewed in this article, and should not be prescribed alone as first line treatments. ORAs should be directed against more specific behavioural targets and their primary usefulness may be as adjuncts to other medications and/or to cognitive and behavioural therapy.
Similar content being viewed by others
References
Goldstein A, Lowney LI, Pal BK. Stereospecific and nonspecific interactions of the morphine congener levorphanol in subcellular fractions of mouse brain. Proc Natl Acad Sci U S A 1971; 68(8): 1742–7
Simon EJ, Hiller JM, Edelman I. Stereospecific binding of the potent narcotic analgesic (3H) etorphine to rat-brain homogenate. Proc Natl Acad Sci U S A 1973; 70(7): 1947–9
Terenius L. Stereospecific interaction between narcotic analgesics and a synaptic plasma membrane fraction of rat cerebral cortex. Acta Pharmacol Toxicol (Copenh) 1973; 32(3): 317–20
Martin WR, Eades CG, Thompson JA, et al. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 1976; 197(3): 517–32
Mansour A, Khachaturian H, Lewis ME, et al. Anatomy of CNS opioid receptors. Trends Neurosci 1988; 11: 308–14
Terenius L, Wahlström A. Search for an endogenous ligand for the opiate receptor. Acta Physiol Scand 1975; 94(1): 74–81
Hughes J, Smith TW, Kosterlitz HW, et al. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 1975; 258(5536): 577–80
Pasternak GW, Goodman R, Snyder SH. An endogenous morphine-like factor in mammalian brain. Life Sci 1975; 16(12): 1765–9
Guillemin R, Ling N, Burgus R. Endorphins, hypothalamic and neurohypophysial peptides with morphinomimetic activity: isolation and molecular structure of alpha-endorphin. C R Acad Sci Hebd Seances Acad Sci D 1976; 282(8): 783–5
Frederickson RCA. Endogenous opioids and related derivatives. In: Kuhar MJ, Pasternak GW, editors. Analgesics: neu- rochemical, behavioral and clinical perspectives. New York: Raven Press, 1984
Höllt V. Multiple endogenous opioid peptides. Trends Neurosci 1983; 6: 24
Olson GA, Olson RD, Kastin AJ. Endogenous opiates: 1992. Peptides 1993; 14(6): 1339–78
Verebey K, Volavka J, Clouet D. Endorphins in psychiatry: an overview and a hypothesis. Arch Gen Psychiatry 1978; 35(7): 877–88
Barchas JD, Evans C, Elliott GR, et al. Peptide neuroregulators: the opioid system as a model. Yale J Biol Med 1985; 58(6): 579–96
Aitkenhead AR, Derbyshire DR, Pinnock CA, et al. Pharmaco-kinetics of intravenous naloxone in healthy volunteers [abstract]. Anesthesiology 1984; 61: A381
Crabtree BL. Review of naltrexone, a long-acting opiate antagonist. Clin Pharm 1984; 3(3): 273–80
Dixon R, Howes J, Gentile J, et al. Nalmefene: intravenous safety and kinetics of a new opioid antagonist. Clin Pharmacol Ther 1986; 39(1): 49–53
Dixon R, Gentile J, Hsu HB, et al. Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist. J Clin Pharmacol 1987; 27(3): 233–9
Kosten TA, Kosten TR. Pharmacological blocking agents for treating substance abuse. J Nerv Ment Dis 1991; 179(10): 583–92
Liffredo C, Gallino G. Naltrexone in the therapeutic relation in cases of opioid abuse and dependence. Minerva Med 1993; 84(12): 687–92
O’Brien C. Recent developments in the pharmacotherapy of substance abuse. J Consult Clin Psychol 1996; 64(4): 677–86
O’Brien C, Volpicelli LA, Volpicelli JR. Naltrexone in the treatment of alcoholism: a clinical review. Alcohol 1996; 13(1): 35–9
Volpicelli JR, Volpicelli LA, O’Brien CP. Medical management of alcohol dependence: clinical use and limitations of naltrexone treatment. Alcohol Alcohol 1995; 30(6): 789–98
Wodak A. Managing illicit drug use. A practical guide. Drugs 1994; 47(3): 446–57
Morley JE. The neuroendocrine control of appetite: the role of the endogenous opiates, cholecystokinin, TRH, gamma-aminobutyric-acid and the diazepam receptor. Life Sci 1980; 27(5): 355–68
Morley JE. Neuropeptide regulation of appetite and weight. Endocr Rev 1987; 8(3): 256–87
Giugliano D. Opioid peptides and obesity. Eur J Med 1992; 1(2): 90–6
Hagan MM, Moss DE. Effect of naloxone and antidepressants on hyperphagia produced by peptide YY. Pharmacol Biochem Behav 1993; 45(4): 941–4
Brewerton TD, Lydiard RB, Laraia MT, et al. CSF betaendorphin and dynorphin in bulimia nervosa. Am J Psychiatry 1992; 149(8): 1086–90
Waller DA, Kiser RS, Hardy BW, et al. Eating behavior and plasma beta-endorphin in bulimia. Am J Clin Nutr 1986; 44(1): 20–3
Fullerton DT, Swift WJ, Getto CJ, et al. Plasma immunoreactive beta-endorphin in bulimics. Psychol Med 1986; 16(1): 59–63
Baranowska B. Are disturbances in opioid and adrenergic systems involved in the hormonal dysfunction of anorexia nervosa? Psychoneuroendocrinology 1990; 15(5–6): 371–9
De Marinis L, Folli G, D’Amico C, et al. Differential effects of feeding on the ultradian variation of the growth hormone (GH) response to GH-releasing hormone in normal subjects and patients with obesity and anorexia nervosa. J Clin Endocrinol Metab 1988; 66(3): 598–604
De Marinis L, Mancini A, Folli G, et al. Naloxone inhibition of postprandial growth hormone releasing hormone-induced growth hormone release in obesity. Neuroendocrinology 1989; 50(5): 529–32
Berga SL, Mortola JF, Girton L, et al. Neuroendocrine aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 1989; 68(2): 301–8
Genazzani AD, Petraglia F, Fabbri G, et al. Evidence of luteinizing hormone secretion in hypothalamic amenorrhea associated with weight loss. Fertil Steril 1990; 54(2): 222–6
Genazzani AR, Genazzani AD, Volpogni C, et al. Opioid control of gonadotrophin secretion in humans. Hum Reprod 1993; 2: 151–3
Genazzani AD, Petraglia F, Gastaldi M, et al. Episodic release of prolactin in women with weight loss-related amenorrhea. Gynecol Endocrinol 1994; 8(2): 95–100
Genazzani AD, Petraglia F, Gastaldi M, et al. Naltrexone treatment restores menstrual cycles in patients with weight loss-related amenorrhea. Fertil Steril 1995; 64(5): 951–6
Zaks A, Jones T, Fink M, et al. Naloxone treatment of opiate dependence. JAMA 1971; 215: 2108–10
Hollister LE, Johnson K, Boukhabza D, et al. Aversive effects of naltrexone in subjects not dependent on opiates. Drug Alcohol Depend 1981; 8: 37–41
Cohen MR, Cohen RM, Pickar D, et al. Naloxone reduces food intake in humans. Psychosom Med 1985; 2: 132–8
Yeomans MR, Wright P, Macleod HA, et al. Effects of nalmefene on feeding in humans. Psychopharmacology (Berl) 1990; 100: 426–32
Bertino M, Beauchamp GK, Engelman K. Naltrexone, an opioid blocker, alters taste perception and nutrient intake in humans. Am J Physiol 1991 Jul; 261 (1 Suppl. Pt 2): R59–R63
Trenchard E, Silverstone T. Naloxone reduces the food intake of normal human volunteers. Appetite 1983; 4: 43–50
Kyriakides M, Silverstone T, Jeffcoate W, et al. Effect of naloxone on hyperphagia in Prader-Willi syndrome [letter]. Lancet 1980; 1(8173): 876–7
Krotkiewski M, Fagerberg B, Bjorntorp P, et al. Endorphins in genetic human obesity. Int J Obes 1983; 7(6): 597–8
Zlotkin SH, Fettes TM, Stallings VA. The effects of naltrexone, an oral beta-endorphin antagonist, in children with the Prader-Willi syndrome. J Clin Endocrinol Metab 1986; 63(5): 1229–32
de Zwaan M, Mitchell JE. Opiate antagonists and eating behavior in humans: a review. J Clin Pharmacol 1992; 32(12): 1060–72
Mitchell JE, Laine DE, Morley JE, et al. Naloxone but not CCK-8 may attenuate binge-eating behavior in patients with the bulimia syndrome. Biol Psychiatry 1986; 21(14): 1399–406
Drewnowski A, Krahn DD, Demitrack MA, et al. Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters. Am J Clin Nutr 1995; 61(6): 1206–12
Jonas JM, Gold MS. Naltrexone reverses bulimic symptoms [letter]. Lancet 1986; 1(8484): 807
Jonas JM, Gold MS. Treatment of antidepressant-resistant bulimia with naltrexone. Int J Psychiatry Med 1986; 16(4): 305–9
Jonas JM, Gold MS. Naltrexone treatment of bulimia: clinical and theoretical findings linking eating disorders and substance abuse. Adv Alcohol Subst Abuse 1987; 7(1): 29–37
Jonas JM, Gold MS. The use of opiate antagonists in treating bulimia: a study of low-dose versus high-dose naltrexone. Psychiatry Res 1988; 24(2): 195–9
Igoin-Apfelbaum L, Apfelbaum M. Naltrexone and bulimic symptoms [letter]. Lancet 1987; 2(8567): 1087–8
Mitchell JE, Christenson G, Jennings J, et al. A placebo-controlled, double-blind crossover study of naltrexone hydrochloride in outpatients with normal weight bulimia. J Clin Psychopharmacol 1989; 9(2): 94–7
Alger SA, Schwalberg MD, Bigaouette JM, et al. Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects. Am J Clin Nutr 1991; 53(4): 865–71
Marrazzi MA, Bacon JP, Kinzie J, et al. Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa. Int Clin Psychopharmacol 1995; 10(3): 163–72
Davidson TL, McKenzie BR, Tujo CJ, et al. Development of tolerance to endogenous opiates activated by 24-h food deprivation. Appetite 1992; 19(1): 1–13
Marrazzi MA, Mullings-Britton J, Stack L, et al. Atypical endogenous opioid systems in mice in relation to an auto-addiction opioid model of anorexia nervosa. Life Sci 1990; 47(16): 1427–35
De Marinis L, Mancini A, Zuppi P, et al. Opioid dysregulation in anorexia nervosa: naloxone effects on preprandial and postprandial growth hormone response to growth hormone-releasing hormone. Metabolism 1994; 43(2): 140–3
Moore R, Mills IH, Forster A. Naloxone in the treatment of anorexia nervosa: effect on weight gain and lipolysis. J R Soc Med 1981; 74(2): 129–31
Luby ED, Marrazzi MA, Kinzie J. Treatment of chronic anorexia nervosa with opiate blockade [letter]. J Clin Psychopharmacol 1987; 7(1): 52–3
Armeanu MC, Berkhout GM, Schoemaker J. Pulsatile luteinizing hormone secretion in hypothalamic amenorrhea, anorexia nervosa, and polycystic ovarian disease during naltrexone treatment. Fertil Steril 1992; 57(4): 762–70
Garcia-Rubi E, Vazquez-Aleman D, Mendez JP, et al. The effects of opioid blockade and GnRH administration upon luteinizing hormone secretion in patients with anorexia nervosa during the stages of weight loss and weight recovery. Clin Endocrinol (Oxf) 1992; 37(6): 520–8
Luby ED, Marrazzi MA, Sperti S. Anorexia nervosa: a syndrome of starvation dependence. Compr Ther 1987; 13(9): 16–21
Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 1984; 7: 309–38
Coid J, Allolio B, Rees LH. Raised plasma metenkephalin in patients who habitually mutilate themselves. Lancet 1983; 2(8349): 545–6
Herman BH. A possible role of proopiomelanocortin peptides in self-injurious behavior [review]. Prog Neuropsychopharmacol Biol Psychiatry 1990; 14Suppl. 39: S109–39
Willemsen-Swinkels SH, Buitelaar JK, Weijnen FG, et al. Plasma beta-endorphin concentrations in people with learning disability and self-injurious and/or autistic behaviour. Br J Psychiatry 1996; 168(1): 105–9
Wang SW, Zhang ZH, Wang R. Norepinephrine and serotonin-induced antinociception are blocked by naloxone with different dosages. Brain Res Bull 1994; 35: 113–7
Richardson JS, Zaleski WA. Naloxone and self mutilation. Biol Psychiatry 1983; 18: 99–101
Lienemann J, Walker F. Naltrexone for treatment of self-injury [letter]. Am J Psychiatry 1989; 146: 1639–40
Roth AS, Ostroff RB, Hoffman RE. Naltrexone as a treatment for repetitive self-injurious behaviour: an open-label trial. J Clin Psychiatry 1996; 57(6): 233–7
Skinner BE. The behaviour of organisms: an experimental analysis. New York: Appletown Century, 1938
Herman BH, Hammock MK, Arthur-Smith A, et al. Naltrexone decreases self-injurious behavior. Ann Neurol 1987; 22(4): 550–2
Bernstein GA, Hughes JR, Mitchell JE, et al. Effects of narcotic antagonists on self-injurious behavior: a single case study. J Am Acad Child Adolesc Psychiatry 1987; 26(6): 886–9
Szymanski L, Kedesdy J, Sulkes S, et al. Naltrexone in treatment of self injurious behavior: a clinical study. Res Dev Disabil 1987; 8(2): 179–90
Leboyer M, Bouvard MP, Dugas M. Effects on naltrexone on infantile autism [letter]. Lancet 1988; 1(8587): 715
Sandman CA. Beta-endorphin dysregulation in autistic and self-injurious behavior: a neurodevelopmental hypothesis. Synapse 1988; 2(3): 193–9
Sandman CA, Barron JL, Colman H. An orally administered opiate blocker, naltrexone, attenuates self-injurious behavior. Am J Ment Retard 1990; 95(1): 93–102
Kars H, Broekema W, Glaudemans-van Gelderen I, et al. Naltrexone attenuates self-injurious behavior in mentally retarded subjects. Biol Psychiatry 1990; 27(7): 741–6
Barrett RP, Feinstein C, Hole WT. Effects of naloxone and naltrexone on self-injury: a double-blind, placebo-controlled analysis. Am J Ment Retard 1989; 93(6): 644–51
Ryan EP, Helsel WJ, Lubetsky MJ, et al. Use of naltrexone in reducing self-injurious behavior: a single case analysis. J Multihandicapped Person 1989; 2: 295–309
Knabe R, Schulz P, Richard J. Initial aggravation of self-injurious behavior in autistic patients receiving naltrexone treatment [letter]. J Autism Dev Disord 1990; 20(4): 591–3
Knabe R, Bovier P. Pharmacological treatment of extreme self-injurious behavior in autism. Eur Psychiatry 1992; 7: 297–8
Leboyer M, Bouvard MP, Launay JM, et al. Brief report: a double-blind study of naltrexone in infantile autism. J Autism Dev Disord 1992; 22(2): 309–19
Walters AS, Barrett RP, Feinstein C, et al. A case report of naltrexone treatment of self-injury and social withdrawal in autism. J Autism Dev Disord 1990; 20(2): 169–76
Taylor DV, Hetrick WP, Neri CL, et al. Effect of naltrexone upon self-injurious behavior, learning and activity: a case study. Pharmacol Biochem Behav 1991; 40(1): 79–82
Ricketts RW, Goza AB, Matese B. Case study: effects of naltrexone and SIB on self-injury. Behav Residential Treatment 1992; 7: 315–26
Zingarelli G, Ellman G, Horn A, et al. Clinical effects of naltrexone on autistic behavior. Am J Ment Retard 1992; 97(1): 57–63
Crews WD Jr, Bonaventura S, Rowe FB, et al. Cessation of long-term naltrexone therapy and self-injury: a case study. Res Dev Disabil 1993; 14(4): 331–40
Campbell M, Anderson LT, Small AM, et al. Naltrexone in autistic children: behavioral symptoms and attentional learning. J Am Acad Child Adolesc Psychiatry 1993; 32(6): 1283–91
Thompson T, Hackenberg T, Cerutti D, et al. Opioid antagonist effects on self-injury in adults with mental retardation: response form and location as determinants of medication effects. Am J Ment Retard 1994; 99(1): 85–102
Willemsen-Swinkels SH, Buitelaar JK, Nijhof GJ, et al. Failure of naltrexone hydrochloride to reduce self-injurious and autistic behavior in mentally retarded adults. Double-blind placebo-controlled studies. Arch Gen Psychiatry 1995; 52(9): 766–73
Benjamin S, Seek A, Tresise L, et al. Case study: paradoxical response to naltrexone treatment of self-injurious behavior. J Am Acad Child Adolesc Psychiatry 1995; 34(2): 238–42
Sonne S, Rubey R, Brady K, et al. Naltrexone treatment of self-injurious thoughts and behaviors. J Nerv Ment Dis 1996; 184(3): 192–5
Herman BH, Hammock MK, Egan J, et al. Role for opioid peptides in self-injurious behavior: dissociation from autonomic nervous system functioning. Dev Pharmacol Ther 1989; 12(2): 81–9
Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 1989; 46(11): 1006–11
Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry 1989; 46(11): 1012–6
Sandyk R. Naloxone abolishes obsessive-compulsive behavior in Tourette’s syndrome. Int J Neurosci 1987; 35(1–2): 93–4
Kurlan R, Majumdar L, Deeley C, et al. A controlled trial of propoxyphene and naltrexone in patients with Tourette’s syndrome. Ann Neurol 1991; 30(1): 19–23
Panksepp J, Herman BH, Vilberg T, et al. Endogenous opioids and social behavior. Neurosci Biobehav Rev 1980; 4(4): 473–87
Panksepp J. A neurochemical theory of autism. Trends Neurosci 1979; 2: 174–7
Sahley TL, Panksepp J. Brain opioids and autism: an updated analysis of possible linkages. J Autism Dev Disord 1987; 17(2): 201–16
Leboyer M, Bouvard MP, Launay JM, et al. Brief report: a double-blind study of naltrexone in infantile autism [see comments]. J Autism Dev Disord 1992; 22(2): 309–19
Tordjman S, Anderson GM, McBride PA, et al. Plasma beta-endorphin, adrenocorticotropin hormone, and Cortisol in autism. J Child Psychol Psychiatry 1997; 38(6): 705–15
Weizman R, Gil-Ad I, Dick J, et al. Low plasma immunoreactive beta-endorphin levels in autism. J Am Acad Child Adolesc Psychiatry 1988; 27(4): 430–3
Sandman CA, Barron JL, Chicz-DeMet A, et al. Brief report: plasma beta-endorphin and Cortisol levels in autistic patients [see comments]. J Autism Dev Disord 1991; 21(1): 83–7
Leboyer M, Bouvard MP, Recasens C, et al. Difference between plasma N- and C-terminally directed beta-endorphin immunoreactivity in infantile autism. Am J Psychiatry 1994; 151(12): 1797–801
Campbell M, Adams P, Small AM, et al. Naltrexone in infantile autism. Psychopharmacol Bull 1988; 24(1): 135–9
Willemsen-Swinkels SH, Buitelaar JK, van Engeland H. The effects of chronic naltrexone treatment in young autistic children: a double-blind placebo-controlled crossover study. Biol Psychiatry 1996; 39(12): 1023–31
Panksepp J, Lensing P. Brief report: a synopsis of an open-trial of naltrexone treatment of autism with four children. J Autism Dev Disord 1991; 21(2): 243–9
Kolmen BK, Feldman HM, Händen BL, et al. Naltrexone in young autistic children: a double-blind, placebo-controlled crossover study. J Am Acad Child Adolesc Psychiatry 1995; 34(2): 223–31
Campbell M, Anderson LT, Small AM, et al. Naltrexone in autistic children: a double-blind and placebo-controlled study. Psychopharmacol Bull 1990; 26(1): 130–5
Bouvard MP, Leboyer M, Launay JM, et al. Low-dose naltrexone effects on plasma chemistries and clinical symptoms in autism: a double-blind, placebo-controlled study. Psychiatry Res 1995; 58(3): 191–201
Willemsen-Swinkels SH, Buitelaar JK, Weijnen FG, et al. Placebo-controlled acute dosage naltrexone study in young autistic children. Psychiatry Res 1995; 58(3): 203–15
Campbell M, Harris JC. Resolved: autistic children should have a trial of naltrexone [discussion 9–51]. J Am Acad Child Adolesc Psychiatry 1996; 35(2): 246–9
Wiegant VM, Verhoef CJ, Burbach JP, et al. Increased concentration of alpha- and gamma-endorphin in post mortem hypo-thalamic tissue of schizophrenic patients. Life Sci 1988; 42(18): 1733–42
Terenius L, Walhström A, Lindström L, et al. Increased CSF levels of endorphins in chronic psychosis. Neurosci Lett 1976; 3: 157–62
Lindstrom LH, Widerlov E, Gunne LM, et al. Endorphins in human cerebrospinal fluid: clinical correlations to some psychotic states. Acta Psychiatr Scand 1978; 57(2): 153–64
Pickar D, Naber D, Post RM, et al. Endorphins in the cerebrospinal fluid of psychiatric patients. Ann N Y Acad Sci 1982; 398: 399–412
Panza G, Monzani E, Sacerdote P, et al. Beta-endorphin, vaso-active intestinal peptide and cholecystokinin in peripheral blood mononuclear cells from healthy subjects and from drug-free and haloperidol-treated schizophrenic patients. Acta Psychiatr Scand 1992; 85(3): 207–10
Bissette G, Nemeroff CB, Mackay AV. Neuropeptides and schizophrenia. Prog Brain Res 1986; 66: 161–74
Pickar D, Bunney WE Jr, Douillet P, et al. Repeated naloxone administration in schizophrenia: a phase II World Health Organization Study. Biol Psychiatry 1989; 25(4): 440–8
Jasinski DR, Martin WR, Haertzen CA. The human pharmacology and abuse potential of N-allyl-noroxy-morphone (naloxone). J Pharmacol Exp Ther 1967; 157: 420–6
Pickar D, Dubois M, Cohen MR. Behavioral change in a cancer patient following intrathecal b-endorphin administration. Am J Psychiatry 1984; 141: 103–4
Jasinski DR, Martin WR, SapiraJD. Antagonism of the subjective behavioral, pupillary, and respiratory depressant effects of cyclazocine by naloxone. Clin Pharmacol Ther 1968; 9: 215–22
Bacopoulos NG, Spokes EG, Bird ED, et al. Antipsychotic drugs action in schizophrenic patients: effects on cortical dopamine metabolism after long-term treatment. Science 1979; 205: 1405–7
Reynolds GP. Increased concentrations and lateral asymmetry of amygdala dopamine in schizophrenia. Nature 1983; 305: 527–9
Toru M, Watanabe S, Shibuya H, et al. Neurotransmitters, receptors and neuropeptides in post-mortem brains of chronic schizophrenic patients. Acta Psychiat Scand 1988; 78: 121–37
Dilts RP, Kalivas PW Localization of mu opioid and neurotensin receptors within the A10 region of the rat. Ann N Y Acad Sci 1988; 26: 684–37
Calenko-Choukroun G, Dauge V, Gacel G, et al. Lesion of dopamine mesolimbic neurons blocks behavioral effects induced by the endogenous enkephalins but not by a mu-receptor opioid agonist. Eur J Pharmacol 1991; 209: 267–71
Lindenmayer JP, Gardner E, Goldberg E, et al. High-dose naloxone in tardive dyskinesia. Psychiatry Res 1988; 26: 19–28
Kurland AA, McCabe OL, Hanlon TE, et al. The treatment of perceptual disturbances in schizophrenia with naloxone hydrochloride. Am J Psychiatry 1977; 134(12): 1408–10
Pickar D,Vartanian F, Bunney WE Jr, et al. Short-term naloxone administration in schizophrenic and manic patients. A World Health Organization Collaborative Study. Arch Gen Psychiatry 1982; 39(3): 313–9
Naber D, Pickar D. The measurement of endorphins in body fluids. Psychiatr Clin North Am 1983; 6(3): 443–56
Verhoeven WM, van Praag HM, van Ree JM. Repeated naloxone administration in schizophrenia. Psychiatry Res 1984; 12(4): 297–312
Mielke DH, Gallant DM. An oral opiate antagonist in chronic schizophrenia: a pilot study. Am J Psychiatry 1977; 134(12): 1430–1
Gitlin MJ, Gerner RH, Rosenblatt M. Assessment of naltrexone in the treatment of schizophrenia. Psychopharmacology (Berl) 1981; 74(1): 51–3
Marchesi GF, Santone G, Cotani P, et al. Naltrexone in chronic negative schizophrenia. Clin Neuropharmacol 1992; 15Suppl. 1 Pt A: 56A–7A
Marchesi GF, Santone G, Cotani P, et al. The therapeutic role of naltrexone in negative symptom schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 1995; 19(8): 1239–49
Becker JA, Goldman MB, Alam MY, et al. Effects of naltrexone on mannerisms and water imbalance in polydipsic schizophrenics: a pilot study. Schizophr Res 1995; 17(3): 279–82
Rapaport MH, Wolkowitz O, Kelsoe JR, et al. Beneficial effects of nalmefene augmentation in neuroleptic-stabilized schizophrenic patients. Neuropsychopharmacology 1993; 9(2): 111–5
Welch EB, Thompson DF. Opiate antagonists for the treatment of schizophrenia. J Clin Pharm Ther 1994; 19(5): 279–83
Kleinman JE, Weinberger DR, Rogol A, et al. Naloxone in chronic schizophrenic patients: neuroendocrine and behavioral effects. Psychiatry Res 1982; 7(1): 1–7
Orr M, Oppenheimer C. Effects of naloxone on auditory hallucinations (case report). Br Med J 1978; 1: 481
Berger PA, Watson SJ, Akil H, et al. The effects of naloxone in chronic schizophrenia. Am J Psychiatry 1981; 138: 913–8
Cohen MR, Pickar D, Cohen RM. High-dose naloxone administration in chronic schizophrenia. Biol Psychiatry 1985; 20: 570–83
Sethi BB, Prakash R. A study of naloxone with schizophrenia and manic patients. Br J Psychiatry 1981; 138: 501–3
Nishikawa T, Tsuda A, Tanaka M, et al. Naloxone attenuates drinking behavior in psychiatric patients displaying self-induced water intoxication. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18(1): 149–53
Chappell PB, Leckman JF, Pauls D, et al. Biochemical and genetic studies of Tourette’s syndrome. In: Deutsch SI, Weizman A, Weizman R, editors. Application of basic neuroscience to child psychiatry. New York: Plenum, 1990
Nieuwenhuys R, editor. Chemoarchitecture of the brain. New York: Springer-Verlag, 1985
Kuhar MJ, Pert CB, Snyder SH. Regional distribution of opiate receptor binding in monkey and human brain. Nature 1973; 245(5426): 447–50
Herrera-Marschitz M, Christensson-Nylander I, Sharp T, et al. Striato-nigral dynorphin and substance P pathways in the rat. II. Functional analysis. Exp Brain Res 1986; 64(1): 193–207
Haber SN, Kowall NW, Vonsattel JP, et al. Gilles de la Tourette’s syndrome. A postmortem neuropathological and immunohistochemical study. J Neurol Sci 1986; 75(2): 225–41
Leckman JF, Riddle MA, Berrettini WH, et al. Elevated CSF dynorphin A [1–8] in Tourette’s syndrome. Life Sci 1988; 43(24): 2015–23
Lichter D, Majumdar L, Kurlan R. Opiate withdrawal unmasks Tourette’s syndrome. Clin Neuropharmacol 1988; 11(6): 559–64
Walters AS, Hening W, Chokroverty S. Opioid therapy in the movement disorders [letter]. Mov Disord 1990; 5(1): 89–90
Gillman MA, Sandyk R. Tourette syndrome and the opioid system [letter]. Psychiatry Res 1985; 15(2): 161–2
Chappell PB, Leckman JF, Riddle MA, et al. Neuroendocrine and behavioral effects of naloxone in Tourette syndrome. Adv Neurol 1992; 58: 253–62
McConville BJ, Norman AB, Fogelson MH, et al. Sequential use of opioid antagonists and agonists in Tourette’s syndrome [letter]. Lancet 1994; 343(8897): 601
Weeks RA, Lees AJ, Brooks DJ. Tourette’s syndrome and the opioid system [letter]. Lancet 1994; 343(8905): 1107–8
Frankel M, Cummings JL, Robertson MM, et al. Obsessions and compulsions in Gilles de la Tourette’s syndrome. Neurology 1986; 36(3): 378–82
Pauls DL, Towbin KE, Leckman JF, et al. Gilles de la Tourette’s syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship. Arch Gen Psychiatry 1986; 43(12): 1180–2
Leckman JF, Knorr AM, Rasmusson AM, et al. Basal ganglia research and Tourette’s syndromes [letter]. Trends Neurosci 1991; 14(3): 94
Leckman JF, Cohen DJ. Tic disorders. In: Rutter M, Taylor E, Hersov L, editors. Child and adolescent psychiatry: modern approaches. Third ed. Oxford: Blackwell Science, 1994
Villablanca JR, Olmstead CE, de Andres I. Naloxone cancels compulsory approaching syndrome in cats without the caudate nuclei. Soc Neurosci Abstr 1992; 18
Insel TR, Pickar D. Naloxone administration in obsessive-compulsive disorder: report of two cases. Am J Psychiatry 1983; 140(9): 1219–20
Keuler DJ, Altemus M, Michelson D, et al. Behavioral effects of naloxone infusion in obsessive-compulsive disorder. Biol Psychiatry 1996; 40(2): 154–6
Stein DJ, Mullen L, Islam MN, et al. Compulsive and impulsive symptomatology in trichotillomania. Psychopathology 1995; 28(4): 208–13
Stein DJ, Simeon D, Cohen LJ, et al. Trichotillomania and obsessive-compulsive disorder. J Clin Psychiatry 1995; 4: 28–34
Swedo SE, Leonard HL. Trichotillomania. An obsessive compulsive spectrum disorder? Psychiatr Clin North Am 1992; 15(4): 777–90
Rapoport JL, Ryland DH, Kriete M. Drug treatment of canine acral lick. An animal model of obsessive-compulsive disorder. Arch Gen Psychiatry 1992; 49(7): 517–21
Dodman NH, Shuster L, White SD, et al. Use of narcotic antagonists to modify Stereotypie self-licking, self-chewing, and scratching behavior in dogs. J Am Vet Med Assoc 1988; 193(7): 815–9
White SD. Naltrexone for treatment of acral lick dermatitis in dogs. J Am Vet Med Assoc 1990; 196(7): 1073–6
Christenson GA, Mackenzie TB, Mitchell JE. Characteristics of 60 adult chronic hair pullers. Am J Psychiatry 1991; 148: 365–70
Christenson GA, Raymond NC, Faris PL, et al. Pain thresholds are not elevated in trichotillomania. Biol Psychiatry 1994; 36(5): 347–9
Christenson GA, Crow SJ, Mackenzie TB, et al. A placebo controlled double-blind study of naltrexone for trichotillomania [abstract]. In: New Research Program and Abstracts of the 150th annual meeting of the American Psychiatric Association: 1994, May 26; Philadelphia, abstract NR597: 212
Carrion VG. Naltrexone for the treatment of trichotillomania: a case report [letter]. J Clin Psychopharmacol 1995; 15(6): 444–5
Hockings GI, Grice JE, Ward WK, et al. Hypersensitivity of the hypothalamic-pituitary-adrenal axis to naloxone in post-traumatic-stress-disorder. Biol Psychiatry 1993; 33: 585–93
van der Kolk BA, Greenberg MS, Orr SP, et al. Endogenous opioids, stress induced analgesia, and posttraumatic stress disorder. Psychopharmacol Bull 1989; 25(3): 417–21
Glover H. A preliminary trial of nalmefene for the treatment of emotional numbing in combat veterans with post-traumatic stress disorder. Isr J Psychiatry Relat Sci 1993; 30(4): 255–63
Bach-y—Rita G. Habitual violence and self-mutilation. Am J Psychiatry 1974; 131: 1018–20
Pattison EM, Kahan J. The deliberate self-harm syndrome. Am J Psychiatry 1983; 140: 867–72
Putman F: Dissociation as a response to extreme trauma. In: Kluft R, editor. The Childhood Antecedents of Multiple Personality. Washington DC: American Psychiatric Press, 1985
Kosten TR. Client issues in drug abuse treatment: addressing multiple drug abuse. NIDA Res Monogr 1991; 106: 136–51
O’Brien C, Volpicelli LA, Volpicelli JR. Naltrexone in the treatment of alcoholism: a clinical review. Alcohol 1996; 13(1): 35–9
O’Brien C. Recent developments in the pharmacotherapy of substance abuse. J Consult Clin Psychol 1996; 64(4): 677–86
O’Brien C. Overview: the treatment of drug dependence. Addiction 1994; 89(11): 1565–9
O’Brien C. A range of research-based pharmacotherapies for addiction. Science 1997; 278(5335): 66–70
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rénéric, JP., Bouvard, M.P. Opioid Receptor Antagonists in Psychiatry. Mol Diag Ther 10, 365–382 (1998). https://doi.org/10.2165/00023210-199810050-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00023210-199810050-00006