A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents.
OBJECTIVE
Preclinical findings suggest that the over-the-counter supplement N-acetylcysteine (NAC), via glutamate modulation in the nucleus accumbens, holds promise as a pharmacotherapy for substance dependence. The authors investigated NAC as a novel cannabis cessation treatment in adolescents, a vulnerable group for whom existing treatments have shown limited efficacy.


METHODS
In an 8-week double-blind randomized placebo-controlled trial, treatment-seeking cannabis-dependent adolescents (ages 15-21 years; N=116) received NAC (1200 mg) or placebo twice daily as well as a contingency management intervention and brief (&lt;10 minutes) weekly cessation counseling. The primary efficacy measure was the odds of negative weekly urine cannabinoid test results during treatment among participants receiving NAC compared with those receiving placebo, in an intent-to-treat analysis. The primary tolerability measure was frequency of adverse events, compared by treatment group.


RESULTS
Participants receiving NAC had more than twice the odds, compared with those receiving placebo, of having negative urine cannabinoid test results during treatment (odds ratio=2.4, 95% CI=1.1-5.2). Exploratory secondary abstinence outcomes favored NAC but were not statistically significant. NAC was well tolerated, with minimal adverse events.


CONCLUSIONS
This is the first randomized controlled trial of pharmacotherapy for cannabis dependence in any age group to yield a positive primary cessation outcome in an intent-to-treat analysis. Findings support NAC as a pharmacotherapy to complement psychosocial treatment for cannabis dependence in adolescents.
Department of Psychiatry and Behavioral Sciences, the Hollings Cancer Center, Charleston, SC, USA.graykm@musc.edu
Kevin M
KM
Gray
Matthew J
MJ
Carpenter
Nathaniel L
NL
Baker
Stacia M
SM
DeSantis
Elisabeth
E
Kryway
Karen J
KJ
Hartwell
Aimee L
AL
McRae-Clark
Kathleen T
KT
Brady
D000111:Acetylcysteine / Q000627:therapeutic use*; D000293:Adolescent; D002186:Cannabinoids / Q000652:urine; D003376:Counseling; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
D002186:Cannabinoids; D018691:Excitatory Amino Acid Antagonists; D000111:Acetylcysteine