Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: Two double-blind, randomized, clinical trials

Marc E. Mooney, Joy M. Schmitz, F. Gerard Moeller, John Grabowski

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Rationale: The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use. Objective: The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence. Methods: In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR®). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies. Results: L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood. Conclusion: These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed.

Original languageEnglish (US)
Pages (from-to)214-223
Number of pages10
JournalDrug and alcohol dependence
Volume88
Issue number2-3
DOIs
StatePublished - May 11 2007

Fingerprint

Cocaine-Related Disorders
Levodopa
Cocaine
Randomized Controlled Trials
Safety
Placebos
Therapeutics
Drug therapy
levodopa drug combination carbidopa
Carbidopa
Delayed-Action Preparations
Blood Pressure
Drug Therapy
Carboxy-Lyases
Medication Adherence
Blood pressure
Dizziness
Nausea
Dopamine
Pharmacology

Keywords

  • Carbidopa
  • Cocaine
  • Dopamine
  • L-dopa
  • Levodopa
  • Side effects

Cite this

Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence : Two double-blind, randomized, clinical trials. / Mooney, Marc E.; Schmitz, Joy M.; Moeller, F. Gerard; Grabowski, John.

In: Drug and alcohol dependence, Vol. 88, No. 2-3, 11.05.2007, p. 214-223.

Research output: Contribution to journalArticle

@article{c82eef037a124e94ae686b059733b632,
title = "Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence: Two double-blind, randomized, clinical trials",
abstract = "Rationale: The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use. Objective: The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence. Methods: In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR{\circledR}). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies. Results: L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood. Conclusion: These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed.",
keywords = "Carbidopa, Cocaine, Dopamine, L-dopa, Levodopa, Side effects",
author = "Mooney, {Marc E.} and Schmitz, {Joy M.} and Moeller, {F. Gerard} and John Grabowski",
year = "2007",
month = "5",
day = "11",
doi = "10.1016/j.drugalcdep.2006.10.011",
language = "English (US)",
volume = "88",
pages = "214--223",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
publisher = "Elsevier Ireland Ltd",
number = "2-3",

}

TY - JOUR

T1 - Safety, tolerability and efficacy of levodopa-carbidopa treatment for cocaine dependence

T2 - Two double-blind, randomized, clinical trials

AU - Mooney, Marc E.

AU - Schmitz, Joy M.

AU - Moeller, F. Gerard

AU - Grabowski, John

PY - 2007/5/11

Y1 - 2007/5/11

N2 - Rationale: The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use. Objective: The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence. Methods: In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR®). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies. Results: L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood. Conclusion: These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed.

AB - Rationale: The role of dopamine in cocaine abuse has been long recognized. Cocaine use can profoundly alter dopaminergic functioning through depletion of this monoamine and changes in receptor functioning. Based on these facts, levodopa (L-dopa) pharmacotherapy may be helpful in reducing or abolishing cocaine use. Objective: The current studies sought to evaluate the safety, tolerability and efficacy of L-dopa as a treatment for cocaine dependence. Methods: In Study 1, 67 cocaine-dependent subjects were randomized in a 5-week, double-blind, placebo-controlled safety trial. Subjects received either placebo, or 400 mg L-dopa plus 100 mg of the peripheral decarboxylase inhibitor, carbidopa, in a sustained-release preparation (Sinemet CR®). In Study 2, 122 cocaine-dependent subjects were enrolled in a 9-week, randomized, double-blind, placebo-controlled trial to compare placebo to 400/100 mg and 800/200 mg L-dopa/carbidopa treatments. Placebo or L-dopa were administered twice daily in both studies. Results: L-dopa was well tolerated with similar retention and medication adherence rates compared to placebo. Only two side effects occurred more often in L-dopa-treated patients: nausea and dizziness. L-dopa lowered diastolic blood pressure in a dose-dependent fashion. In these trials, L-dopa had no effect on cocaine use, cocaine craving, or mood. Conclusion: These two studies demonstrate the safety and tolerability of L-dopa pharmacotherapy in cocaine-dependent patients. No evidence for greater efficacy of L-dopa compared to placebo was observed. The possibility of enhancing treatment effects by combining L-dopa with other behavioral or pharmacological interventions is discussed.

KW - Carbidopa

KW - Cocaine

KW - Dopamine

KW - L-dopa

KW - Levodopa

KW - Side effects

UR - http://www.scopus.com/inward/record.url?scp=33947655476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947655476&partnerID=8YFLogxK

U2 - 10.1016/j.drugalcdep.2006.10.011

DO - 10.1016/j.drugalcdep.2006.10.011

M3 - Article

C2 - 17134849

AN - SCOPUS:33947655476

VL - 88

SP - 214

EP - 223

JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

SN - 0376-8716

IS - 2-3

ER -