title: Prescription opioid analgesics rapidly change the human brain.
abstract: Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High-resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor-based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage-correlated volumetric decrease was observed primarily in the right amygdala. Dosage-correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow-up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine-induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward- and affect-processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid-induced gray matter changes.
authors.affiliation: Department of Anesthesia, School of Medicine, Stanford University, Palo Alto, CA, USA Department of Human Biology, School of Arts & Sciences, Stanford University, Palo Alto, CA, USA.
authors.forename: Jarred W
authors.initials: JW
authors.lastname: Younger
authors.forename: Larry F
authors.initials: LF
authors.lastname: Chu
authors.forename: Nicole T
authors.initials: NT
authors.lastname: D'Arcy
authors.forename: Kiley E
authors.initials: KE
authors.lastname: Trott
authors.forename: Laura E
authors.initials: LE
authors.lastname: Jastrzab
authors.forename: Sean C
authors.initials: SC
authors.lastname: Mackey
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D017116:Low Back Pain / Q000188:drug therapy / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D010147:Pain Measurement; D055553:Prescription Drugs / Q000494:pharmacology / Q000627:therapeutic use; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D055553:Prescription Drugs; D009020:Morphine