Opiate Withdrawal Using Clonidine

Gold, Mark S.

doi:10.1001/jama.1980.03300300021018

Cited by 252 publications

(14 citation statements)

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“…As noted above, clonidine has modest efficacy in suppressing opioid withdrawal though it can also produce excessive sedation or hypotension (37,38,41) and generally results in less-favorable outcomes than detoxification using methadone or buprenorphine (41,46,51,52). Advantages of clonidine include that it is not a controlled substance, has little risk of diversion or abuse, and can reduce the delay between stopping opioids and starting naltrexone.…”

Section: Detoxification With Clonidine and Other Nonopioid Medicationsmentioning

confidence: 99%

Opioid Detoxification and Naltrexone Induction Strategies: Recommendations for Clinical Practice

Sigmon

Bisaga

Nunes

et al. 2012

The American Journal of Drug and Alcohol Abuse

106

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Background Opioid dependence is a significant public health problem associated with high risk for relapse if treatment is not ongoing. While maintenance on opioid agonists (i.e., methadone, buprenorphine) often produces favorable outcomes, detoxification followed by treatment with the μ-opioid receptor antagonist naltrexone may offer a potentially useful alternative to agonist maintenance for some patients. Method Treatment approaches for making this transition are described here based on a literature review and solicitation of opinions from several expert clinicians and scientists regarding patient selection, level of care, and detoxification strategies. Conclusion Among the current detoxification regimens, the available clinical and scientific data suggest that the best approach may be using an initial 2–4 mg dose of buprenorphine combined with clonidine, other ancillary medications, and progressively increasing doses of oral naltrexone over 3–5 days up to the target dose of naltrexone. However, more research is needed to empirically validate the best approach for making this transition.

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Section: Detoxification With Clonidine and Other Nonopioid Medicationsmentioning

confidence: 99%

Opioid Detoxification and Naltrexone Induction Strategies: Recommendations for Clinical Practice

Sigmon

Bisaga

Nunes

et al. 2012

The American Journal of Drug and Alcohol Abuse

106

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“…Clonidine, an alpha-2-noradrenergic agonist, is known to inhibit the firing of LC neurons (Aghajanian 1978) A comparison of the effects of clonidine and CNQX infusion into the locus coeruleus and the amygdala on naloxone-precipitated opiate withdrawal in the rat drawal (Freedman and Aghajanian 1985). The efficacy of clonidine to treat opioid dependency by reducing the occurrence of withdrawal signs and symptoms (Gold et al 1978(Gold et al , 1980Uhde et al 1980;Washton et al 1980;Charney et al 1981Charney et al , 1982Redmond 1981) may be due to the fact that alpha-2 adrenoceptor and opiate receptor agonists operate through common intracellular effector mechanisms in regions such as the LC and amygdala. Stimulation of either alpha-2 or opiate receptors is known to mediate alterations in the cAMP pathway, as clonidine-or morphine-induced hyperpolarization of LC neurons can be reversed by administration of cAMP analogs which activate protein kinase A (PKA; Aghajanian and Wang 1987).…”

Section: Introductionmentioning

confidence: 99%

A comparison of the effects of clonidine and CNQX infusion into the locus coeruleus and the amygdala on naloxone-precipitated opiate withdrawal in the rat

1998

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Both the locus coeruleus (LC) and the amygdala have been implicated in aspects of opiate dependence and withdrawal. The LC is known to be one of the most sensitive sites for precipitating withdrawal behaviors after local opiate antagonist infusions in morphine-dependent subjects. The amygdala is also known to mediate antagonist-induced withdrawal behaviors and aversive motivational states. The goal of the present study was to evaluate directly the ability of noradrenergic agonists and glutamatergic antagonists to attenuate naloxone-precipitated withdrawal behaviors when infused into the LC or the central nucleus of the amygdala (CeA). The alpha-2-noradrenergic agonists clonidine or ST-91 were infused into the CeA to compare the effects of noradrenergic activation in the CeA to the attenuation of withdrawal previously observed in rats infused with clonidine into the LC, since the LC and CeA are known to contain co-localized opiate and noradrenergic receptors. The effects of microinfusions of the non-NMDA excitatory amino acid antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) were also infused into the LC and CeA since opiate withdrawal is associated with increased glutamatergic transmission. Intra-CeA clonidine or ST-91 (2.4 microg/0.5 microl or 1.0 microl) produced significant reductions primarily in the occurrence of irritability. Conversely, intra-CeA or intra-LC infusions of CNQX (2.5 microg/0.5 microl) significantly attenuated naloxone-precipitated withdrawal, an effect similar to the attenuation previously observed after intra-LC clonidine infusions. These data demonstrate the specific behavioral effects of altering glutamatergic and noradrenergic neurotransmission in the LC or CeA during naloxone-precipitated opiate withdrawal. Elucidation of the neuroanatomical circuitry involved in opiate withdrawal should increase our understanding of the neuroadaptations associated with drug dependence and subsequent withdrawal behavior.

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“…Clonidine, an alpha-2-adrenergic agonist, has been used effectively in the treatment of opioid dependency to minimize withdrawal signs and symptoms (Gold et al 1978(Gold et al , 1980Washton and Resnick 1980;Uhde et al 1980;Charney et al 1981Charney et al , 1982. There is substantial evidence that increased brain noradrenergic activity during the abstinence syndrome may be partly responsible for the manifest withdrawal state in animals.…”

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confidence: 99%

Clonidine infusions into the locus coeruleus attenuate behavioral and neurochemical changes associated with naloxone-precipitated withdrawal

et al. 1988

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Clonidine, an alpha-2-adrenergic agonist, suppresses signs of opiate withdrawal in animals and in man. Electrical or chemical stimulation of the nucleus locus coeruleus (LC) increases noradrenergic activity and brain concentration of the noradrenergic metabolite MHPG, and produces many signs of opiate withdrawal. Thus, clonidine's ability to attenuate withdrawal might be due to the reduction of noradrenergic neuronal activity originating in the LC, but additional alpha-2-adrenergic receptors throughout the body and other mechanisms may also play a role. The present study explored the neuroanatomical and pharmacological selectivity of alpha-2-adrenergic receptors of the LC in the anti-withdrawal action of clonidine. Experiment 1 tested the hypothesis that behavioral and biochemical measures of naloxone-precipitated withdrawal from morphine would be blocked by infusions of clonidine (0.6 or 2.4 micrograms/microliters) into the LC. Significant reductions were observed in the occurrence of diarrhea, ptosis, weight loss and wet-dog shakes. Clonidine also reversed the naloxone-precipitated increase in hippocampus MHPG concentration. In experiment 2 subjects received an LC infusion or IP injection of a non-lipophilic alpha-2-agonist (ST-91), which does not penetrate the blood-brain barrier, or of clonidine into the dorsal parabrachial nucleus (DPB) to test the selectivity of the effects of clonidine infusions into the LC. ST-91 infusions into the LC reduced several of the observed withdrawal signs and increased others (e.g., jumping). Although peripheral injections of ST-91 attenuated some of the checked signs associated with naloxone-precipitated withdrawal, the frequency of wet-dog shakes was not reduced. ST-91 infusions into the LC, but not systemic ST-91 administration, prevented the withdrawal-induced increase in hippocampus MHPG concentration. Clonidine infused lateral to the LC into the DPB did not significantly attenuate withdrawal or reduce hippocampus MHPG levels. These results provide behavioral and biochemical evidence to support the suggestion that clonidine significantly attenuates naloxone-precipitated withdrawal through an interaction with noradrenergic neurons located in the vicinity of the LC.

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Opiate Withdrawal Using Clonidine

Cited by 252 publications

References 14 publications

Opioid Detoxification and Naltrexone Induction Strategies: Recommendations for Clinical Practice

Opioid Detoxification and Naltrexone Induction Strategies: Recommendations for Clinical Practice

A comparison of the effects of clonidine and CNQX infusion into the locus coeruleus and the amygdala on naloxone-precipitated opiate withdrawal in the rat

Clonidine infusions into the locus coeruleus attenuate behavioral and neurochemical changes associated with naloxone-precipitated withdrawal

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