Naltrexone Implant for the Treatment of Polydrug Dependence: A Randomized Controlled Trial

Tiihonen, Jari; Krupitsky, Evgeny; Verbitskaya, E.; Blokhina, Elena; Mamontova, Olga; Föhr, Jaana; Tuomola, Pekka; Kuoppasalmi, Kimmo; Kiviniemi, Vesa; Zwartau, Edwin

doi:10.1176/appi.ajp.2011.11071121

Cited by 88 publications

(99 citation statements)

References 22 publications

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“…Taken together, this study provides support for the notion that NTX may be useful for the treatment of MA dependence, thus extending upon positive trials for stimulant dependence (Jayaram-Lindstrom et al, 2008a) and polydrug dependence (Tiihonen et al, 2012). Although no clinical trials to date have tested NTX for the treatment of MA dependence, with the exception of a small combination study (Grant et al, 2010), the present work suggests that such trials may be warranted.…”

Section: Discussionsupporting

confidence: 71%

“…A clinical trial of a NTX depot implant demonstrated significant benefit over placebo on measures of treatment retention, drug-free urines, and global assessments of functioning in a hard-totreat sample of heroin and amphetamine polydrugdependent individuals (Tiihonen et al, 2012). Further, a recent behavioral pharmacology study found that acute oral NTX significantly reduced craving during cocaine administration in a sample of non-treatment-seeking cocaine users (n = 12) (Comer et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Ray

Bujarski

Courtney

et al. 2015

Neuropsychopharmacol

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Methamphetamine (MA) use disorder is a serious psychiatric condition for which there are no FDA-approved medications. Naltrexone (NTX) is an opioid receptor antagonist with demonstrated efficacy, albeit moderate, for the treatment of alcoholism and opioid dependence. Preclinical and clinical studies suggest that NTX may be useful for the treatment of MA use disorder. To inform treatment development, we conducted a double-blind, randomized, crossover, placebo-controlled human laboratory study of NTX. Non-treatmentseeking individuals meeting DSM-IV criteria for MA abuse or dependence (n = 30) completed two separate 5-day inpatient stays. During each admission, participants completed testing sessions comprised of MA cue-reactivity and intravenous MA administration (30 mg) after receiving oral NTX (50 mg) or placebo for 4 days. This study tested the hypotheses that NTX would (a) attenuate cue-induced MA craving, and (b) reduce subjective responses to MA administration. Results largely supported the study hypotheses such that (a) NTX significantly blunted cue-induced craving for MA and (b) attenuated several of the hedonic subjective effects of MA, including craving, during controlled MA administration and as compared with placebo. NTX decreased overall subjective ratings of 'crave drug,' 'stimulated,' and 'would like drug access,' decreased the the post-MA administration timecourse of 'anxious' and increased ratings of 'bad drug effects,' as compared with placebo. These findings support a potential mechanism of action by showing that NTX reduced cue-induced craving and subjective responses to MA. This is consistent with positive treatment studies of NTX for amphetamine dependence, as well as ongoing clinical trials for MA.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Ray

Bujarski

Courtney

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…It also improved the global clinical condition of the patients. This study suggested naltrexone use as an option for treating polydrug dependence with psychostimulant drugs (Tiihonen et al, 2012). However, in other studies, no beneficial effects of naltrexone were reported in cocaine-and alcoholdependent outpatients when combined with psychotherapy or drug counseling (Schmitz, Stotts, Sayre, DeLaune, & Grabowski, 2004).…”

Section: Naltrexonementioning

confidence: 64%

Psychostimulants

McCreary

Müller

Filip

2015

International Review of Neurobiology

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“…A common concern with treatments that target a specific class of drugs (e.g., methadone for opioid abuse) is that individuals will switch to other drugs of abuse such as amphetamines (Tiihonen, et al, 2012). CocH vector treatment would be vulnerable to this issue.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase

Smethells

Swalve

Brimijoin

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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A promising approach in treating cocaine abuse is to metabolize cocaine in the blood using a mutated butyrylcholinesterase (BChE) that functions as a cocaine hydrolase (CocH). In rats, a helper-dependent adenoviral (hdAD) vector-mediated delivery of CocH abolished ongoing cocaine use and cocaine-primed reinstatement of drug-seeking for several months. This enzyme also metabolizes ghrelin, an effect that may be beneficial in maintaining healthy weights. The effect of a single hdAD-CocH vector injection was examined in rats on measures of anxiety, body weight, cocaine self-administration, and cocaine-induced locomotor activity. To examine anxiety, periadolescent rats were tested in an elevated-plus maze. Weight gain was then examined under four rodent diets. Ten months after CocH-injection, adult rats were trained to self-administer cocaine intravenously and, subsequently, cocaine-induced locomotion was tested. Viral gene transfer produced sustained plasma levels of CocH for over 13 months of testing. CocH-treated rats did not differ from controls in measures of anxiety, and only showed a transient reduction in weight gain during the first 3 weeks postinjection. However, CocH-treated rats were insensitive to cocaine. At 10 months postinjection, none of the CocH-treated rats initiated cocaine self-administration, unlike 90% of the control rats. At 13 months postinjection, CocH-treated rats showed no cocaineinduced locomotion, whereas control rats showed a dosedependent enhancement of locomotion. CocH vector produced a long-term blockade of the rewarding and behavioral effects of cocaine in rats, emphasizing its role as a promising therapeutic intervention in cocaine abuse.

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Naltrexone Implant for the Treatment of Polydrug Dependence: A Randomized Controlled Trial

Abstract: Naltrexone implants resulted in higher retention in the study, decreased heroin and amphetamine use, and improved clinical condition for patients, thus providing the first evidence of an effective pharmacological treatment for this type of polydrug dependence.

Cited by 88 publications

References 22 publications

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

Psychostimulants

Long-Term Blockade of Cocaine Self-Administration and Locomotor Activation in Rats by an Adenoviral Vector-Delivered Cocaine Hydrolase

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