TABLE 3.

CLINICAL TRIALS OF GLT-1 MODULATION FOR SUBSTANCE USE/COMPULSIVITY

Reference	Patient population	Pharmacotherapy	Study design	Study length	Number of subjects	Results of primary outcome	Results of secondary outcome
(58)	Bipolar disorder with incidental alcohol or tobacco use	NAC	Double blind RCT	20 weeks plus 4 week washout	75	Decreased depressive symptoms (published in Berk, Copolov et al. 2008)	No decrease in incidental tobacco or alcohol use
(82)	Cannabis dependent adolescents	NAC	Double blind RCT	8 weeks	89	No difference in self-reported craving
(81)	Cannabis dependent adolescents	NAC	Open-label	4 weeks	24	NAC is well-tolerated with few adverse effects that are mild or moderate	Decreased self-reported use and craving; no change in urine metabolites
(83)	Cannabis dependent adolescents	NAC	Double blind RCT	8 weeks	116	Decreased cannabinoid-positive urines
(68)	Cannabis dependent adolescents who also smoked cigarettes	NAC	Double blind RCT	8 weeks	68	No differences in cigarettes smoked	Placebo group showed poorer cannabis outcomes for cigarette smokers than non-smokers
(34)	Cocaine dependence	NAC	Double blind RCT	8 weeks	111	No differences in cocaine-negative urines or self-reported cocaine use	Increased delay to relapse for patients abstinent at beginning of trial in dose-dependent fashion (High dose NAC >Low dose NAC > Placebo)
(36)	Cocaine dependence	NAC	Double blind cross-over	3 days inpatient for each condition, separated by one week	13	NAC is well-tolerated with few adverse effects that are mild or moderate	Decreased self-reported craving during study for NAC participants but was not different from placebo
(35)	Cocaine dependence	NAC	Double blind cross-over	3 days inpatient for each condition, separated by one week	15	Decreased viewing time, self-reported interest and self-reported craving when viewing cocaine slides in NAC vs. placebo	No changes in physiological measures
(37)	Cocaine dependence	NAC	Open-label dose finding	4 weeks	23	NAC is well-tolerated up to 3600 mg/day	Decreased self-reported use, craving, and money spent on cocaine
(31)	Cocaine dependence	NAC vs. baclofen	Double blind cross-over (no placebo)	4 days per treatment separated by one week	6	NAC decreases self-reported craving induced by an IV infusion of cocaine, but does not decrease the “high” or “rush” associated with the cocaine
(70)	Comorbid nicotine dependence and pathological gambling	NAC	Double blind RCT	12 weeks w/additional 3 month follow up	28	For NAC vs. placebo: Early, transient decrease in nicotine dependence; delayed decrease in gambling dependence severity	N/A
(78)	Methamphetamine dependence	NAC + naltrexone	Double blind RCT w/dose escalation; NAC group also received naltrexone	8 weeks	31	No difference in self-reported craving	No difference in self-reported use or methamphetamine-negative urines
(71)	Nicotine dependence	NAC + varenicline	Open label	4 weeks	19	Tolerable and safe, with mainly mild side effects and high medication adherence	Reduction in cigarettes per day
(67)	Nicotine dependence (mild)	NAC	Double blind RCT	3 days	22	NAC decreases self-reported rewarding effects of first cigarette smoked after a period of abstinence, and slightly reduces withdrawal symptoms but does not decrease craving
(69)	Nicotine users w/o regard to dependence status	NAC	Double blind RCT	6 monts	41	Decreased mutagenicity in bronchoalveolar lavage samples	No change in smoking but participants were specifically instructed not to decrease their levels of smoking
(62)	Nicotine dependence	NAC	Double blind RCT	4 weeks	29	Decrease in number of cigarettes smoked, after exclusion of two heavy alcohol drinkers	No changes in carbon monoxide or cravings
(85)	Pathological gambling	NAC	Open label trial with dose escalation to identify responders followed by double blind RCT	8 weeks (open label), 6 weeks (RCT)	27 (open label), 13 (RCT)	Open label responders had 30% reduction in gambling symptoms,	5/6 on NAC remained responders at end of RCT, 2/7 on placebo remained responders at end of RCT
(86)	Trichotillomania	NAC	Double blind RCT w/dose escalation	12 weeks	50	Decreased hair pulling symptoms for NAC (large effect size)