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

or resolved entirely by the time of discharge. The use of highly successful in enabling patients to cease opioid use
clonidine for opioid detoxification may pave the way for abruptly and maintain abstinence long enough to commence
naltrexone maintenance in many clinical settings and naltrexone treatment. However, the sedative and hypotensive
might also succeed with patients receiving methadone side effects associated with clonidine have constrained its
doses up to 50 mg/day. 56 clinical utility, particularly among outpatients, prompting
exploration into alternative alpha-2 noradrenergic agonists
This development of clonidine and naltrexone as a
treatment for opioid addiction demonstrates the translation that may offer similar anti-withdrawal efficacy without
the undesirable side effects of clonidine. Initial outpatient
of neurobiological advances into new and effective evaluations of lofexidine, a structural analog of clonidine,
clinical approaches. Naltrexone provides a chronic opioid suggest that it could be equally effective for opioid
receptor blockade, which prevents opioid intoxication and detoxification and potentially more suitable for outpatient
subsequent re-addiction in recovery. This sequential use management if it lacks the sedation and hypotension
of naltrexone for opioid receptor blockade, in conjunction occasionally observed with clonidine. 64
with clonidine to treat withdrawal symptomatology during
65
rehabilitation, represents a viable and effective treatment Blum et al. developed a protocol that included the
for opioid addiction in motivated patients. neuronutrient KB220Z and other anti-withdrawal agents,
such as clonidine, to investigate initial detoxification
3.1. Summary of the clonidine/naltrexone approach from OUD in treatment centers, with particularly heavily
to opioid withdrawal dependent OUD subjects. Among the 17 subjects in the
Gold et al. summarized experiences with the clonidine/ study, only three were administered buprenorphine/
58
naltrexone approach in motivated OUD patients. naloxone (Bup/Nx) alongside KB220Z. Initially, in this
Clonidine hydrochloride, an alpha-adrenergic agonist, is a pilot phase, five patients received 6 days of KB220Z at a
non-opioid medication that, when used in detoxification dosage of 2 oz twice daily before meals, in conjunction
from opioids, exhibits rapid suppression of the signs and with clonidine, benzodiazepines, and other adjunctive
symptoms associated with opioid withdrawal. Studies medications such as gabapentin to manage nausea and
have demonstrated that clonidine is useful in detoxifying sleep disturbances. Subsequently, the second protocol
for withdrawal from methadone maintenance patients, involved 12 patients receiving a higher dose of 4 oz every
achieving zero dosage in <14 days with a high success 6 h for 6 days. Only three individuals experienced relapse
rate, compared to the usual 3 – 6 months. In a clinical within the initial 2 weeks, while the remaining 14 subjects
investigation, clonidine suppressed opioid withdrawal remained on KB220Z without requiring additional Bup/
symptomatology in patients on doses of up to 75 mg of Nx for periods ranging from 120 to 214 days.
methadone daily, and shorter-acting narcotics withdrawn Due to the inclusion of standard detoxification agents,
in less than a week. To prevent relapse, post-detoxification definitive conclusions regarding the effects of KB220Z
counseling and the use of the narcotic antagonist, cannot be drawn. However, the fact that only three out
naltrexone, are recommended. 37 of 17 subjects needed Bup/Nx is notable. If corroborated
Clonidine’s ability to reverse opioid withdrawal by larger, more comprehensive studies, this opioid/opioid
syndrome in acute withdrawal and anti-craving studies detoxification approach could offer a novel strategy
supported the NE hypothesis and suggested a new use for for managing withdrawal without relying on addictive
clonidine. 32,55,59-63 The effectiveness of lofexidine provided opioids. Combining alpha-2 agonist therapy with KB220Z,
further validation for the noradrenaline (NA) hypothesis. a pro-dopamine regulator, may emerge as a frontline
Clonidine has been demonstrated to be a potent emergency option alongside other treatment modalities. Notably,
intervention for acute opioid withdrawal, facilitating neuroimaging studies comparing KB220Z and placebo
detoxification from methadone, heroin, and other opioids. have demonstrated robust and specific blood oxygen level-
66
By reversing cognitive, affective, and physiological dependent dopamine activation in animal models and
67
manifestations of withdrawal, clonidine not only alleviates abstinent heroin addicts, suggesting putative induction
immediate symptoms but also maintain suppression of of “dopamine homeostasis.”
their reoccurrence when administered over a period of Previously, Blum et al. published several articles
10 – 14 days within a detoxification regimen. 55,59 arguing against the long-term utilization of opioid agonists

Clonidine appears most appropriate for clinical such as methadone and buprenorphine, except for harm
66-90
application as a transitional intervention bridging opioid reduction, but did not favor their prophylaxis use.
dependence and naltrexone therapy. A 10-day outpatient In terms of post-withdrawal treatment options, many
detoxification regimen involving clonidine has proven articles discuss opioid agonists and narcotic antagonism,

Volume 7 Issue 3 (2024) 7 doi: 10.36922/itps.1918