A randomized, double-blind, placebo-controlled study of the kappa opioid receptor antagonist, CERC-501, in a human laboratory model of smoking behavior

Jermaine D. Jones, Shanna Babalonis, Ronald Marcus, Bradley Vince, Debra Kelsh, Michelle R. Lofwall, Heather Fraser, Blake Paterson, Suky Martinez, Diana M. Martinez, Edward V. Nunes, Sharon L. Walsh, Sandra D. Comer

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Preclinical data indicate that selective kappa opioid receptor antagonists reduce nicotine self-administration and withdrawal symptoms. The aim of the current study was to determine whether treatment with CERC-501, an orally available, potent, and selective kappa opioid receptor antagonist, could alleviate nicotine withdrawal and craving and mitigate mood alterations associated with nicotine withdrawal in humans. Healthy, adult cigarette smokers were enrolled into this randomized, multisite, double-blind, placebo-controlled, crossover study. Participants completed two 8-day treatment phases during which they received either CERC-501 (15 mg, p.o., once daily) or placebo. On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing. The primary outcome measures were (a) performance on the McKee Smoking Lapse test (ie, latency to smoke in exchange for money) and (b) number of cigarettes self-administered during a 60-minute ad lib smoking period. Other outcomes included measures of craving, mood, anxiety, nicotine withdrawal, and subjective effects of cigarette smoking. A total of 71 participants who smoked an average of approximately 23 cigarettes per day were enrolled, and 56 subjects completed the study. CERC-501 was well tolerated, but it did not significantly alter the latency to start smoking (CERC-501: 16.5 min vs placebo: 17.7 min) or the number of cigarettes smoked (CERC-501: 3.3 cigarettes vs placebo: 3.1 cigarettes). Compared with placebo, CERC-501 also did not affect cigarette craving, mood, anxiety, nicotine withdrawal, or subjective effects of smoking. These findings do not support a role for CERC-501 in the treatment of nicotine use disorder.

Original languageEnglish
Article numbere12799
JournalAddiction Biology
Volume25
Issue number4
DOIs
StatePublished - Jul 1 2020

Bibliographical note

Funding Information:
This study was funded by Cerecor Inc and by National Institute on Drug Abuse (NIDA) grant R01DA040976 to Drs Blake Paterson (PI, former CEO of Cerecor Inc.), Sandra Comer (co‐PI), and Sharon Walsh (co‐PI). NIDA played no role in the data analysis or publication of this manuscript. Cerecor contributed to the design of this study as well as preparation, review, and approval of the manuscript. Data analyses were performed by a third party (Algorithme Pharma Inc.); however, Drs Comer and Walsh were provided with full access to all study data.

Publisher Copyright:
© 2019 Society for the Study of Addiction

Keywords

  • CERC-501
  • kappa opioid receptor
  • nicotine withdrawal
  • smoking cessation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

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