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Published in: Journal of Medical Case Reports 1/2022

Open Access 01-12-2022 | Buprenorphine | Case report

The partial µ-opioid agonist buprenorphine in autism spectrum disorder: a case report

Authors: Charlotte Skoglund, Siri Leknes, Markus Heilig

Published in: Journal of Medical Case Reports | Issue 1/2022

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Abstract

Background

There are currently no approved medications for impaired social cognition and function, core symptoms of autism spectrum disorder. We describe marked improvement of these symptoms with long-term low-dose administration of the partial µ-opioid agonist buprenorphine. We discuss these observations in the context of a role for endogenous opioid systems in social attachment, and theories integrating those findings mechanistically with autism spectrum disorder.

Case presentation

M, a 43-year-old Caucasian male, is medically healthy. Despite social difficulties since childhood, he completed high school with better-than-average grades, but failed university education. A psychiatric evaluation in his twenties diagnosed attention deficit hyperactivity disorder but also noted symptoms of coexisting autism spectrum disorder. M accidentally came across buprenorphine in his late twenties and experienced progressively improved social functioning on a low daily dosage (0.5–1.0 mg/day), an effect maintained for 15 years. He lived independently and maintained a part-time occupation. After abrupt discontinuation of treatment, his autistic symptoms returned, and function deteriorated. Following evaluation by our team, buprenorphine was resumed, with gradual return to prior level of functioning. An attempt to formally evaluate M both on and off medication was agreed with him and approved by the Swedish Ethics Authority, but medication had to be resumed when the patient worsened following discontinuation.

Conclusions

According to the µ-opioid receptor balance model, both excessive and deficient μ-receptor activity may negatively influence social behavior, and accordingly both opioid agonist and opioid antagonist treatment may be able to improve social functioning, depending on an individual’s opioid tone before treatment. Our case report is consistent with these hypotheses, and given the extensive unmet medical needs in individuals with autism spectrum disorders, randomized controlled trial appears warranted.
Literature
3.
go back to reference Christ SE, Holt DD, White DA, Green L. Inhibitory control in children with autism spectrum disorder. J Autism Dev Disord. 2007;37(6):1155–65.PubMedCrossRef Christ SE, Holt DD, White DA, Green L. Inhibitory control in children with autism spectrum disorder. J Autism Dev Disord. 2007;37(6):1155–65.PubMedCrossRef
4.
go back to reference Kenworthy L, Yerys BE, Anthony LG, Wallace GL. Understanding executive control in autism spectrum disorders in the lab and in the real world. Neuropsychol Rev. 2008;18(4):320–38.PubMedPubMedCentralCrossRef Kenworthy L, Yerys BE, Anthony LG, Wallace GL. Understanding executive control in autism spectrum disorders in the lab and in the real world. Neuropsychol Rev. 2008;18(4):320–38.PubMedPubMedCentralCrossRef
5.
go back to reference Lugnegard T, Hallerback MU, Gillberg C. Psychiatric comorbidity in young adults with a clinical diagnosis of Asperger syndrome. Res Dev Disabil. 2011;32(5):1910–7.PubMedCrossRef Lugnegard T, Hallerback MU, Gillberg C. Psychiatric comorbidity in young adults with a clinical diagnosis of Asperger syndrome. Res Dev Disabil. 2011;32(5):1910–7.PubMedCrossRef
6.
go back to reference Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008;47(8):921–9.PubMedCrossRef Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008;47(8):921–9.PubMedCrossRef
7.
go back to reference Jonsson U, Alaie I, Lofgren Wilteus A, Zander E, Marschik PB, Coghill D, et al. Annual research review: quality of life and childhood mental and behavioural disorders - a critical review of the research. J Child Psychol Psychiatry. 2017;58(4):439–69.PubMedCrossRef Jonsson U, Alaie I, Lofgren Wilteus A, Zander E, Marschik PB, Coghill D, et al. Annual research review: quality of life and childhood mental and behavioural disorders - a critical review of the research. J Child Psychol Psychiatry. 2017;58(4):439–69.PubMedCrossRef
8.
go back to reference Bishop-Fitzpatrick L, Mazefsky CA, Eack SM. The combined impact of social support and perceived stress on quality of life in adults with autism spectrum disorder and without intellectual disability. Autism. 2018;22(6):703–11.PubMedCrossRef Bishop-Fitzpatrick L, Mazefsky CA, Eack SM. The combined impact of social support and perceived stress on quality of life in adults with autism spectrum disorder and without intellectual disability. Autism. 2018;22(6):703–11.PubMedCrossRef
9.
go back to reference Hirvikoski T, Mittendorfer-Rutz E, Boman M, Larsson H, Lichtenstein P, Bolte S. Premature mortality in autism spectrum disorder. Br J Psychiatry. 2016;208(3):232–8.PubMedCrossRef Hirvikoski T, Mittendorfer-Rutz E, Boman M, Larsson H, Lichtenstein P, Bolte S. Premature mortality in autism spectrum disorder. Br J Psychiatry. 2016;208(3):232–8.PubMedCrossRef
10.
go back to reference Brugha TS, Spiers N, Bankart J, Cooper SA, McManus S, Scott FJ, et al. Epidemiology of autism in adults across age groups and ability levels. Br J Psychiatry. 2016;209(6):498–503.PubMedCrossRef Brugha TS, Spiers N, Bankart J, Cooper SA, McManus S, Scott FJ, et al. Epidemiology of autism in adults across age groups and ability levels. Br J Psychiatry. 2016;209(6):498–503.PubMedCrossRef
11.
go back to reference Idring S, Lundberg M, Sturm H, Dalman C, Gumpert C, Rai D, et al. Changes in prevalence of autism spectrum disorders in 2001–2011: findings from the Stockholm youth cohort. J Autism Dev Disord. 2015;45(6):1766–73.PubMedCrossRef Idring S, Lundberg M, Sturm H, Dalman C, Gumpert C, Rai D, et al. Changes in prevalence of autism spectrum disorders in 2001–2011: findings from the Stockholm youth cohort. J Autism Dev Disord. 2015;45(6):1766–73.PubMedCrossRef
12.
go back to reference Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet. 2006;368(9531):210–5.PubMedCrossRef Baird G, Simonoff E, Pickles A, Chandler S, Loucas T, Meldrum D, et al. Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP). Lancet. 2006;368(9531):210–5.PubMedCrossRef
13.
go back to reference Siegel M, Beaulieu AA. Psychotropic medications in children with autism spectrum disorders: a systematic review and synthesis for evidence-based practice. J Autism Dev Disord. 2012;42(8):1592–605.PubMedCrossRef Siegel M, Beaulieu AA. Psychotropic medications in children with autism spectrum disorders: a systematic review and synthesis for evidence-based practice. J Autism Dev Disord. 2012;42(8):1592–605.PubMedCrossRef
14.
go back to reference Williams K, Brignell A, Randall M, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2013;8:CD004677. Williams K, Brignell A, Randall M, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2013;8:CD004677.
15.
go back to reference LeClerc S, Easley D. Pharmacological therapies for autism spectrum disorder: a review. P & T Peer-Rev J Formul Manag. 2015;40(6):389–97. LeClerc S, Easley D. Pharmacological therapies for autism spectrum disorder: a review. P & T Peer-Rev J Formul Manag. 2015;40(6):389–97.
16.
go back to reference Jobski K, Hofer J, Hoffmann F, Bachmann C. Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review. Acta Psychiatr Scand. 2017;135(1):8–28.PubMedCrossRef Jobski K, Hofer J, Hoffmann F, Bachmann C. Use of psychotropic drugs in patients with autism spectrum disorders: a systematic review. Acta Psychiatr Scand. 2017;135(1):8–28.PubMedCrossRef
17.
go back to reference Amorim P, Lecrubier Y, Weiller E, Hergueta T, Sheehan D. DSM-IH-R Psychotic Disorders: procedural validity of the Mini International Neuropsychiatric Interview (MINI). Concordance and causes for discordance with the CIDI. Eur Psychiatry. 1998;13(1):26–34.PubMedCrossRef Amorim P, Lecrubier Y, Weiller E, Hergueta T, Sheehan D. DSM-IH-R Psychotic Disorders: procedural validity of the Mini International Neuropsychiatric Interview (MINI). Concordance and causes for discordance with the CIDI. Eur Psychiatry. 1998;13(1):26–34.PubMedCrossRef
18.
go back to reference Lecavalier L, Aman MG, Scahill L, McDougle CJ, McCracken JT, Vitiello B, et al. Validity of the autism diagnostic interview-revised. Am J Ment Retard. 2006;111(3):199–215.PubMedCrossRef Lecavalier L, Aman MG, Scahill L, McDougle CJ, McCracken JT, Vitiello B, et al. Validity of the autism diagnostic interview-revised. Am J Ment Retard. 2006;111(3):199–215.PubMedCrossRef
19.
go back to reference Maddox BB, Brodkin ES, Calkins ME, Shea K, Mullan K, Hostager J, et al. The accuracy of the ADOS-2 in identifying autism among adults with complex psychiatric conditions. J Autism Dev Disord. 2017;47(9):2703–9.PubMedPubMedCentralCrossRef Maddox BB, Brodkin ES, Calkins ME, Shea K, Mullan K, Hostager J, et al. The accuracy of the ADOS-2 in identifying autism among adults with complex psychiatric conditions. J Autism Dev Disord. 2017;47(9):2703–9.PubMedPubMedCentralCrossRef
20.
go back to reference Yen CF, Hwang AW, Liou TH, Chiu TY, Hsu HY, Chi WC, et al. Validity and reliability of the Functioning Disability Evaluation Scale-Adult Version based on the WHODAS 2.0–36 items. J Formos Med Assoc. 2014;113(11):839–49.PubMedCrossRef Yen CF, Hwang AW, Liou TH, Chiu TY, Hsu HY, Chi WC, et al. Validity and reliability of the Functioning Disability Evaluation Scale-Adult Version based on the WHODAS 2.0–36 items. J Formos Med Assoc. 2014;113(11):839–49.PubMedCrossRef
21.
go back to reference Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption–II. Addiction. 1993;88(6):791–804.PubMedCrossRef Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption–II. Addiction. 1993;88(6):791–804.PubMedCrossRef
22.
go back to reference Reinert DF, Allen JP. The Alcohol Use Disorders Identification Test (AUDIT): a review of recent research. Alcohol Clin Exp Res. 2002;26(2):272–9.PubMedCrossRef Reinert DF, Allen JP. The Alcohol Use Disorders Identification Test (AUDIT): a review of recent research. Alcohol Clin Exp Res. 2002;26(2):272–9.PubMedCrossRef
23.
go back to reference Berman AH, Palmstierna T, Kallmen H, Bergman H. The self-report drug use disorders identification test: extended (DUDIT-E): reliability, validity, and motivational index. J Subst Abuse Treat. 2007;32(4):357–69.PubMedCrossRef Berman AH, Palmstierna T, Kallmen H, Bergman H. The self-report drug use disorders identification test: extended (DUDIT-E): reliability, validity, and motivational index. J Subst Abuse Treat. 2007;32(4):357–69.PubMedCrossRef
24.
go back to reference van de Glind G, van den Brink W, Koeter MW, Carpentier PJ, van Emmerik-van OK, Kaye S, et al. Validity of the Adult ADHD Self-Report Scale (ASRS) as a screener for adult ADHD in treatment seeking substance use disorder patients. Drug Alcohol Depend. 2013;132(3):587–96.PubMedPubMedCentralCrossRef van de Glind G, van den Brink W, Koeter MW, Carpentier PJ, van Emmerik-van OK, Kaye S, et al. Validity of the Adult ADHD Self-Report Scale (ASRS) as a screener for adult ADHD in treatment seeking substance use disorder patients. Drug Alcohol Depend. 2013;132(3):587–96.PubMedPubMedCentralCrossRef
25.
go back to reference Wang HR, Woo YS, Ahn HS, Ahn IM, Kim HJ, Bahk WM. The validity of the mood disorder questionnaire for screening bipolar disorder: a meta-analysis. Depress Anxiety. 2015;32(7):527–38.PubMedCrossRef Wang HR, Woo YS, Ahn HS, Ahn IM, Kim HJ, Bahk WM. The validity of the mood disorder questionnaire for screening bipolar disorder: a meta-analysis. Depress Anxiety. 2015;32(7):527–38.PubMedCrossRef
28.
go back to reference Greenwald MK, Comer SD, Fiellin DA. Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. Drug Alcohol Depend. 2014;144:1–11.PubMedCrossRef Greenwald MK, Comer SD, Fiellin DA. Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy. Drug Alcohol Depend. 2014;144:1–11.PubMedCrossRef
29.
go back to reference Machin AJ, Dunbar RIM. The brain opioid theory of social attachment: a review of the evidence. Behaviour. 2011;148(9–10):985–1025.CrossRef Machin AJ, Dunbar RIM. The brain opioid theory of social attachment: a review of the evidence. Behaviour. 2011;148(9–10):985–1025.CrossRef
30.
go back to reference Trezza V, Damsteegt R, Achterberg EJM, Vanderschuren LJMJ. Nucleus accumbens μ-opioid receptors mediate social reward. J Neurosci. 2011;31(17):6362–70.PubMedPubMedCentralCrossRef Trezza V, Damsteegt R, Achterberg EJM, Vanderschuren LJMJ. Nucleus accumbens μ-opioid receptors mediate social reward. J Neurosci. 2011;31(17):6362–70.PubMedPubMedCentralCrossRef
31.
go back to reference Burkett JP, Spiegel LL, Inoue K, Murphy AZ, Young LJ. Activation of μ-opioid receptors in the dorsal striatum is necessary for adult social attachment in monogamous prairie voles. Neuropsychopharmacology. 2011;36(11):2200–10.PubMedPubMedCentralCrossRef Burkett JP, Spiegel LL, Inoue K, Murphy AZ, Young LJ. Activation of μ-opioid receptors in the dorsal striatum is necessary for adult social attachment in monogamous prairie voles. Neuropsychopharmacology. 2011;36(11):2200–10.PubMedPubMedCentralCrossRef
32.
go back to reference Barr CS, Schwandt ML, Lindell SG, Higley JD, Maestripieri D, Goldman D, et al. Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proc Natl Acad Sci USA. 2008;105(13):5277–81.PubMedPubMedCentralCrossRef Barr CS, Schwandt ML, Lindell SG, Higley JD, Maestripieri D, Goldman D, et al. Variation at the mu-opioid receptor gene (OPRM1) influences attachment behavior in infant primates. Proc Natl Acad Sci USA. 2008;105(13):5277–81.PubMedPubMedCentralCrossRef
33.
go back to reference Chelnokova O, Laeng B, Eikemo M, Riegels J, Løseth G, Maurud H, et al. Rewards of beauty: the opioid system mediates social motivation in humans. Mol Psychiatry. 2014;19:746–7.PubMedCrossRef Chelnokova O, Laeng B, Eikemo M, Riegels J, Løseth G, Maurud H, et al. Rewards of beauty: the opioid system mediates social motivation in humans. Mol Psychiatry. 2014;19:746–7.PubMedCrossRef
34.
go back to reference Chelnokova O, Laeng B, Løseth G, Eikemo M, Willoch F, Leknes S. The µ-opioid system promotes visual attention to faces and eyes. Soc Cogn Affect Neurosci. 2016;11(12):1902–9.PubMedPubMedCentralCrossRef Chelnokova O, Laeng B, Løseth G, Eikemo M, Willoch F, Leknes S. The µ-opioid system promotes visual attention to faces and eyes. Soc Cogn Affect Neurosci. 2016;11(12):1902–9.PubMedPubMedCentralCrossRef
35.
go back to reference Syal S, Ipser J, Terburg D, Solms M, Panksepp J, Malcolm-Smith S, et al. Improved memory for reward cues following acute buprenorphine administration in humans. Psychoneuroendocrinology. 2015;53:10–5.PubMedCrossRef Syal S, Ipser J, Terburg D, Solms M, Panksepp J, Malcolm-Smith S, et al. Improved memory for reward cues following acute buprenorphine administration in humans. Psychoneuroendocrinology. 2015;53:10–5.PubMedCrossRef
36.
go back to reference Bershad AK, Seiden JA, de Wit H. Effects of buprenorphine on responses to social stimuli in healthy adults. Psychoneuroendocrinology. 2016;63:43–9.PubMedCrossRef Bershad AK, Seiden JA, de Wit H. Effects of buprenorphine on responses to social stimuli in healthy adults. Psychoneuroendocrinology. 2016;63:43–9.PubMedCrossRef
37.
go back to reference Bershad AK, Ruiz NA, de Wit H. Effects of buprenorphine on responses to emotional stimuli in individuals with a range of mood symptomatology. Int J Neuropsychopharmacol. 2018;21(2):120–7.PubMedCrossRef Bershad AK, Ruiz NA, de Wit H. Effects of buprenorphine on responses to emotional stimuli in individuals with a range of mood symptomatology. Int J Neuropsychopharmacol. 2018;21(2):120–7.PubMedCrossRef
38.
go back to reference Løseth GE, Eikemo M, Isager P, Holmgren J, Laeng B, Vindenes V, et al. Morphine reduced perceived anger from neutral and implicit emotional expressions. Psychoneuroendocrinology. 2018;91:123–31.PubMedCrossRef Løseth GE, Eikemo M, Isager P, Holmgren J, Laeng B, Vindenes V, et al. Morphine reduced perceived anger from neutral and implicit emotional expressions. Psychoneuroendocrinology. 2018;91:123–31.PubMedCrossRef
39.
go back to reference Buchel C, Miedl S, Sprenger C. Hedonic processing in humans is mediated by an opioidergic mechanism in a mesocorticolimbic system. Elife. 2018;7:e39648.PubMedPubMedCentralCrossRef Buchel C, Miedl S, Sprenger C. Hedonic processing in humans is mediated by an opioidergic mechanism in a mesocorticolimbic system. Elife. 2018;7:e39648.PubMedPubMedCentralCrossRef
41.
go back to reference Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG. Endogenous opioids and social behavior. Neurosci Biobehav Rev. 1980;4(4):473–87.PubMedCrossRef Panksepp J, Herman BH, Vilberg T, Bishop P, DeEskinazi FG. Endogenous opioids and social behavior. Neurosci Biobehav Rev. 1980;4(4):473–87.PubMedCrossRef
42.
go back to reference Panksepp J. A neurochemical theory of autism. Trends Neurosci. 1979;2:174–7.CrossRef Panksepp J. A neurochemical theory of autism. Trends Neurosci. 1979;2:174–7.CrossRef
43.
go back to reference Roy A, Roy M, Deb S, Unwin G, Roy A. Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. J Intellect Disabil Res. 2015;59(4):293–306.PubMedCrossRef Roy A, Roy M, Deb S, Unwin G, Roy A. Are opioid antagonists effective in attenuating the core symptoms of autism spectrum conditions in children: a systematic review. J Intellect Disabil Res. 2015;59(4):293–306.PubMedCrossRef
44.
go back to reference Moles A, Kieffer BL, D’Amato FR. Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science. 2004;304(5679):1983–6.PubMedCrossRef Moles A, Kieffer BL, D’Amato FR. Deficit in attachment behavior in mice lacking the mu-opioid receptor gene. Science. 2004;304(5679):1983–6.PubMedCrossRef
45.
go back to reference Becker JAJ, Clesse D, Spiegelhalter C, Schwab Y, Le Merrer J, Kieffer BL. Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity. Neuropsychopharmacology. 2014;39(9):2049–60.PubMedPubMedCentralCrossRef Becker JAJ, Clesse D, Spiegelhalter C, Schwab Y, Le Merrer J, Kieffer BL. Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity. Neuropsychopharmacology. 2014;39(9):2049–60.PubMedPubMedCentralCrossRef
46.
go back to reference Pellissier LP, Gandia J, Laboute T, Becker JAJ, Le Merrer J. mu opioid receptor, social behaviour and autism spectrum disorder: reward matters. Br J Pharmacol. 2018;175(14):2750–69.PubMedCrossRef Pellissier LP, Gandia J, Laboute T, Becker JAJ, Le Merrer J. mu opioid receptor, social behaviour and autism spectrum disorder: reward matters. Br J Pharmacol. 2018;175(14):2750–69.PubMedCrossRef
47.
go back to reference Preuss CV, Kalava A, King KC. Prescription of controlled substances: benefits and risks. Treasure Island: StatPearls; 2022. Preuss CV, Kalava A, King KC. Prescription of controlled substances: benefits and risks. Treasure Island: StatPearls; 2022.
48.
go back to reference Gollust SE, Haselswerdt J. A crisis in my community? Local-level awareness of the opioid epidemic and political consequences. Soc Sci Med. 2021;291:114497.PubMedCrossRef Gollust SE, Haselswerdt J. A crisis in my community? Local-level awareness of the opioid epidemic and political consequences. Soc Sci Med. 2021;291:114497.PubMedCrossRef
Metadata
Title
The partial µ-opioid agonist buprenorphine in autism spectrum disorder: a case report
Authors
Charlotte Skoglund
Siri Leknes
Markus Heilig
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Medical Case Reports / Issue 1/2022
Electronic ISSN: 1752-1947
DOI
https://doi.org/10.1186/s13256-022-03384-w

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