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INNOSC Theranostics and
Pharmacological Sciences Alpha-2A receptor agonist and addiction

including alpha-2 stimulation with agents such as the immediate impacts of buprenorphine on neurological
clonidine and lofexidine. While some of these articles responses to cues associated with heroin. The functional
may be somewhat cryptic, they expand understanding magnetic resonance imaging (fMRI) investigation
of this important topic. 60-62,91,92 Other important novel provided insights into the neurobiological mechanisms
therapeutic modalities include repetitive transcranial underlying addiction and relapse, as well as the therapeutic
magnetic stimulation, 93-101 exercise, 102-107 and precision effects of buprenorphine. While under the influence of
addiction management, which couples genetic addiction buprenorphine, neurological responses to cues associated
risk testing 67,69,73,73,76-79,81,82,88,89,108-113 with pro-dopamine with heroin diminished notably in regions including the
regulation. 65,72,72,82,111-121 amygdala, hippocampus, ventral tegmental area, and
thalamus. However, no significant changes were observed
4. Long-term use of opioid agonists in the ventral striatum, orbital-prefrontal-parietal cortices,
engendering antireward or the cingulate gyrus. This absence of response in the
Physicians treat opioid-dependent patients with an cingulate gyrus underscores its partial role in the process
office-based maintenance program using buprenorphine, of relapse.
a partial mu-opioid receptor agonist. Basic science Neuropsychological and functional neuroimaging
predicted and clinical experiences have confirmed evidence converges to indicate that the dorsal anterior
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that buprenorphine effectively controls opioid cingulate cortex (dACC) is dysfunctional in substance
withdrawal in OUD treatment, especially in fentanyl abuse. Yücel et al. investigated the biochemical and
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use disorders. Patients often prefer opioid replacement physiological properties of the dACC. Using fMRI
with detoxification and abstinence or detoxification and proton magnetic resonance spectroscopy ( H-
1
and naltrexone. Buprenorphine is more effective than MRS), researchers investigated the biochemistry and
abstinence or placebo for managing opioid addiction; physiological activity of the dorsal anterior cingulate cortex
however, if high doses are needed, it may not be superior (dACC) during a behavioral control task in 24 individuals
to methadone. Treatment phases include induction, with opioid dependence. This group was compared to 24
stabilization, and maintenance. The treatment outcome gender-, intelligence-, age-, and performance-matched
is comparable to lower doses of methadone. However, healthy subjects. While both groups exhibited comparable
the current “standard of care” necessitates the initiation levels of activation in the dACC during the task, the
of buprenorphine therapy at the onset of withdrawal opioid-dependent group showed heightened task-related
symptoms, adjusted to address symptoms and craving activation in frontal, parietal, and cerebellar regions,
severity. The advantages of buprenorphine include some alongside reductions in concentrations of N-acetyl
reversal of anhedonia, good availability for office use, and aspartate and glutamate/glutamine in the dACC. Moreover,
somewhat lower abuse potential. Disadvantages include the opioid-dependent group failed to demonstrate the
lack of effectiveness and high cost in patients who would anticipated correlations between dACC activation and
require high methadone doses. behavioral measures of cognitive control. These findings
However, as a cautionary note, while short-term therapy suggest that long-term opioid dependence may result in
with buprenorphine appears very appropriate, this may not biochemical and physiological abnormalities in the dACC.
be the case for prolonged maintenance therapy. The Bup/Nx Individuals with OUD may necessitate increased
combination has acute benefits for the treatment of heroin activation of the frontoparietal and cerebellar networks
use disorder (HUD) but not for relapse prevention and involved in behavioral regulation to achieve normal levels
may increase the probability of relapse. 123-125 Specifically, of task performance and behavioral control. Tailoring
opioid agonists, such as methadone and buprenorphine, treatment to the specific needs of patients who are most
are clinically effective in reducing withdrawal and susceptible to the effects of chronic opioid administration
craving during heroin detoxification but fail to reduce the appears prudent. In addition, Mei et al. observed an
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likelihood of relapse after detoxification. unaltered fMRI response to heroin-related cues in various
Neuroimaging studies have significantly enhanced brain regions, including the ventral striatum, orbital,
our comprehension of why methadone or buprenorphine parietal, lateral, and PFC, indicating a lack of modulation
often fall short in reducing the likelihood of relapse. These by buprenorphine. This lack of buprenorphine effect on
findings, widely recognized for their reliability, shed light these key brain regions linked to relapse may explain its
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on the neurobiological mechanisms underlying relapse limited therapeutic effects on relapse. For a review of
and aid in the development of more effective therapeutic the effects of opioid agonists on dACC function, see Lin
strategies. Mei et al. conducted research investigating et al., who found positive effects on emotional reactivity
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Volume 7 Issue 3 (2024) 8 doi: 10.36922/itps.1918