Minocycline attenuates oxycodone-induced positive subjective responses in non-dependent, recreational opioid users.
Adult
Analgesia
/ methods
Analgesics, Opioid
/ administration & dosage
Anti-Bacterial Agents
/ administration & dosage
Double-Blind Method
Drug Therapy, Combination
/ methods
Female
Humans
Male
Microglia
/ metabolism
Middle Aged
Minocycline
/ administration & dosage
New York
Opioid-Related Disorders
/ prevention & control
Oxycodone
/ administration & dosage
Reward
Young Adult
Abuse potential
Microglia
Minocycline
Opioid
Journal
Pharmacology, biochemistry, and behavior
ISSN: 1873-5177
Titre abrégé: Pharmacol Biochem Behav
Pays: United States
ID NLM: 0367050
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
10
11
2020
revised:
16
07
2021
accepted:
16
07
2021
pubmed:
24
7
2021
medline:
23
2
2022
entrez:
23
7
2021
Statut:
ppublish
Résumé
Recent data suggest that glial cells may be involved in the analgesic effects and abuse liability of opioids. Preclinical studies have demonstrated that mu-opioid-receptor-selective agonists, such as oxycodone, activate glia and increase the release of cytokines, causing a suppression of opioid-induced analgesic effects. Preclinical studies also show that certain medications, such as the broad-spectrum tetracycline antibiotic minocycline, inhibit opioid-induced glial activation and thereby enhance the analgesic effects of opioids. Importantly, minocycline reduces the rewarding effects of opioids at the same doses that it enhances opioid-induced analgesia. The purpose of the present study was to assess the effects of acute administration of minocycline on the subjective, physiological, and analgesic effects of oxycodone in human research volunteers. This study was a within-subject, randomized, double-blind outpatient study. Participants completed five separate sessions in which they received 0, 100, or 200 mg minocycline (MINO) simultaneously with either 0 or 40 mg oxycodone (OXY). The subjective, physiological, and analgesic effects of OXY were measured before and repeatedly after drug administration. Participants were between 21 and 45 years of age, non-treatment seeking, non-dependent recreational opioid users (N = 12). This study was conducted between 2013 and 2014 at the New York State Psychiatric Institute in New York, NY. MINO 100 and 200 mg were safe and well-tolerated in combination with OXY 40 mg. MINO 200 mg administered with OXY 40 mg attenuated OXY-induced positive subjective effects such as "Good Effect" and "Liking" compared to OXY alone. MINO did not alter the physiological or analgesic effects of OXY. MINO may attenuate the abuse liability of mu-opioid-receptor-selective agonists.
Sections du résumé
BACKGROUND
Recent data suggest that glial cells may be involved in the analgesic effects and abuse liability of opioids. Preclinical studies have demonstrated that mu-opioid-receptor-selective agonists, such as oxycodone, activate glia and increase the release of cytokines, causing a suppression of opioid-induced analgesic effects. Preclinical studies also show that certain medications, such as the broad-spectrum tetracycline antibiotic minocycline, inhibit opioid-induced glial activation and thereby enhance the analgesic effects of opioids. Importantly, minocycline reduces the rewarding effects of opioids at the same doses that it enhances opioid-induced analgesia.
AIMS
The purpose of the present study was to assess the effects of acute administration of minocycline on the subjective, physiological, and analgesic effects of oxycodone in human research volunteers.
DESIGN
This study was a within-subject, randomized, double-blind outpatient study. Participants completed five separate sessions in which they received 0, 100, or 200 mg minocycline (MINO) simultaneously with either 0 or 40 mg oxycodone (OXY). The subjective, physiological, and analgesic effects of OXY were measured before and repeatedly after drug administration.
SETTINGS AND PARTICIPANTS
Participants were between 21 and 45 years of age, non-treatment seeking, non-dependent recreational opioid users (N = 12). This study was conducted between 2013 and 2014 at the New York State Psychiatric Institute in New York, NY.
FINDINGS
MINO 100 and 200 mg were safe and well-tolerated in combination with OXY 40 mg. MINO 200 mg administered with OXY 40 mg attenuated OXY-induced positive subjective effects such as "Good Effect" and "Liking" compared to OXY alone. MINO did not alter the physiological or analgesic effects of OXY.
CONCLUSIONS
MINO may attenuate the abuse liability of mu-opioid-receptor-selective agonists.
Identifiants
pubmed: 34298029
pii: S0091-3057(21)00140-4
doi: 10.1016/j.pbb.2021.173241
pmc: PMC8429209
mid: NIHMS1730721
pii:
doi:
Substances chimiques
Analgesics, Opioid
0
Anti-Bacterial Agents
0
Oxycodone
CD35PMG570
Minocycline
FYY3R43WGO
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
173241Subventions
Organisme : NIDA NIH HHS
ID : P50 DA009236
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA016759
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Références
Mayo Clin Proc. 1987 May;62(5):413-7
pubmed: 3553756
J Pharmacol Exp Ther. 2005 Apr;313(1):449-59
pubmed: 15608071
Brain Behav Immun. 2011 Jun;25 Suppl 1:S165-9
pubmed: 21397005
Pain. 2006 Apr;121(3):219-231
pubmed: 16495005
Pain. 1985 Dec;23(4):345-356
pubmed: 4088697
Clin Transl Oncol. 2007 May;9(5):298-307
pubmed: 17525040
J Pharmacol Exp Ther. 1992 Apr;261(1):62-71
pubmed: 1373189
Drugs. 1975;9(4):251-91
pubmed: 1173232
Drug Alcohol Depend. 1996 Oct;42(2):133-42
pubmed: 8889412
Psychopharmacology (Berl). 2016 Mar;233(5):905-16
pubmed: 26645224
Brain Behav Immun. 2009 Jan;23(1):75-84
pubmed: 18684397
Psychopharmacology (Berl). 2011 Jan;213(1):61-8
pubmed: 20838775
Curr Pain Headache Rep. 2010 Apr;14(2):96-104
pubmed: 20425198
Trends Neurosci. 2014 Mar;37(3):125-35
pubmed: 24388427
Drug Alcohol Depend. 2010 Jun 1;109(1-3):130-8
pubmed: 20079977
J Pain. 2017 Aug;18(8):994-1005
pubmed: 28396046
Trends Neurosci. 2005 Dec;28(12):661-9
pubmed: 16246435
Clin Psychopharmacol Neurosci. 2014 Dec;12(3):180-8
pubmed: 25598820
Clin Infect Dis. 2000 Jan;30(1):237-8
pubmed: 10619782
Psychopharmacol Bull. 1986;22(2):397-401
pubmed: 3774933
Behav Brain Res. 2016 Mar 15;301:96-101
pubmed: 26698398
Trials. 2015 Sep 15;16:410
pubmed: 26374703
J Neuroinflammation. 2004 Jul 30;1(1):14
pubmed: 15285801
J Neurosci Res. 2017 Jan 2;95(1-2):487-499
pubmed: 27870418
Psychopharmacology (Berl). 2012 Apr;220(3):551-7
pubmed: 21956241
Psychol Methods. 2012 Jun;17(2):137-52
pubmed: 22545595
J Hand Surg Am. 2017 Mar;42(3):166-174
pubmed: 28259273
J Neuroinflammation. 2017 Nov 15;14(1):222
pubmed: 29141671
Pain. 2005 Jan;113(1-2):9-19
pubmed: 15621359
Pharmacol Biochem Behav. 2012 Apr;101(2):303-6
pubmed: 22260872
Clin Pharmacol Ther. 1993 May;53(5):570-6
pubmed: 8491067
Brain Behav Immun. 2008 Nov;22(8):1248-56
pubmed: 18706994
Neuropharmacology. 2013 Jan;64:452-63
pubmed: 22735770
Psychopharmacology (Berl). 1997 Jun;131(4):313-20
pubmed: 9226732
Pharmacol Biochem Behav. 2012 Oct;102(4):520-5
pubmed: 22789876
Neurosignals. 2013;21(3-4):184-96
pubmed: 22964800
Horm Behav. 2012 Aug;62(3):243-53
pubmed: 22387107
ACS Chem Neurosci. 2019 Apr 17;10(4):2004-2011
pubmed: 30110531
J Neurochem. 2003 Sep;86(6):1534-44
pubmed: 12950462
J Neurosci. 2001 Apr 15;21(8):2580-8
pubmed: 11306611
Psychopharmacology (Berl). 1999 Apr;143(4):327-38
pubmed: 10367549
Psychopharmacol Bull. 1986;22(2):389-96
pubmed: 3774932
Neuropsychopharmacology. 2011 Jan;36(2):411-22
pubmed: 20980992
Pain. 1987 Aug;30(2):191-197
pubmed: 3670870
Anesthesiology. 2015 Feb;122(2):399-406
pubmed: 25373391
J Pharmacol Exp Ther. 1992 Jun;261(3):985-93
pubmed: 1376362
Immunol Res. 2006;34(3):177-92
pubmed: 16891670
Clin Pharmacol Ther. 1973 Sep-Oct;14(5):852-61
pubmed: 4199710
Psychopharmacology (Berl). 2019 Oct;236(10):2857-2866
pubmed: 30564869
PLoS One. 2012;7(7):e40461
pubmed: 22808165
Pharmacol Biochem Behav. 2009 Mar;92(1):135-40
pubmed: 19041336
Cell Mol Neurobiol. 2020 Sep 14;:
pubmed: 32926257
Brain Behav Immun. 2008 Jan;22(1):114-23
pubmed: 17919885
Can J Physiol Pharmacol. 2016 Mar;94(3):257-64
pubmed: 26745749
Clin Pharmacol Ther. 1974 Oct;16(4):653-8
pubmed: 4422361
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15769-74
pubmed: 9861045
Drug Alcohol Depend. 1978 Nov;3(6):419-28
pubmed: 720211
Pain. 2007 Nov;132 Suppl 1:S124-S133
pubmed: 17904745
J Neurosci. 2003 Apr 1;23(7):2517-21
pubmed: 12684435
J Pharmacol Exp Ther. 1994 Apr;269(1):198-203
pubmed: 8169825
Behav Pharmacol. 2015 Jun;26(4):383-92
pubmed: 25563202
Nat Rev Drug Discov. 2003 Sep;2(9):717-26
pubmed: 12951578
J Pharmacol Exp Ther. 1989 Jul;250(1):184-96
pubmed: 2473187
Pain. 2005 May;115(1-2):71-83
pubmed: 15836971