Medications for alcohol use disorder are understudied in adolescents and young adults. To address this gap, this study tested whether a safe and affordable over-the-counter supplement that could serve as a “medication” actually reduces drinking in youth with alcohol use disorder.
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Despite the prevalence of alcohol use disorder during adolescence and emerging adulthood, treatments are typically developed for, and tested in, adults. Among the three medications currently approved by the US Food and Drug Administration for treating alcohol use disorder, none are indicated for individuals under 18 years of age. Similarly, the few pharmacotherapy trials conducted with youth who meet alcohol use disorder criteria have exclusively evaluated the effects of naltrexone (sometimes prescribed in a once monthly injections known by the brand name Vivitrol), leaving a significant gap in research on other candidate pharmacotherapies. This is critical given that administering effective treatments during these earlier developmental stages can prevent the progression of alcohol use disorder into later adulthood.
N-acetylcysteine (NAC), an affordable over-the-counter supplement with a well-established safety profile, is a potential pharmacotherapy for treating alcohol use disorder in youth.
Preclinical trials suggest NAC may help restore balance to the brain’s glutamate system, which contributes to drug and alcohol cravings when disrupted by substance use. A trial conducted among adults with alcohol use disorder found that NAC reduced the number of drinks consumed per day but had no effect on other alcohol-related outcomes. Other trials conducted with individuals with cannabis use disorder found that NAC reduced co-occurring alcohol consumption in youth and both alcohol consumption and frequency in adults. Building on these promising findings, this study is the first randomized trial to test the efficacy of NAC in youth with alcohol use disorder.
This randomized controlled trial evaluated the utility of NAC in reducing alcohol use among adolescents and young adults with alcohol use disorder. Individuals aged 13 to 25 years who expressed interest in alcohol use treatment were eligible to participate in the study if they met diagnostic criteria for alcohol use disorder and reported moderate or heavy alcohol use based on established adolescent criteria. Of the 133 individuals assessed for eligibility, 126 were randomized to a NAC treatment group (n = 65) or a placebo control group (n = 61). Randomization was double-blinded (meaning both participants and people doing the assessments did not know which condition people were in), occurred in a 1:1 ratio, and stratified by sex and school enrollment status.
Over an 8-week treatment period, treatment group participants received 2,400 mg of NAC per day, while control group participants received a matched placebo. Participants in both groups also received a weekly brief alcohol intervention that was delivered remotely or in person by a licensed clinician. The 30-minute counseling sessions included motivational interviewing and goal-setting activities. Participants remained in their assigned group for the duration of the study, and both groups were treated concurrently.
The study’s primary outcome was the total number of standard drinks consumed during the final 4 weeks of the treatment period; secondary outcomes included the total number of drinking days, heavy drinking days (4+ for females and 5+ for males in a single day), and drinks per drinking day during the same period. Baseline alcohol use was assessed using structured interviews, and participants reported their alcohol consumption via daily electronic surveys throughout the treatment period. Follow-up assessments were conducted at 12 and 24 weeks post-baseline. Medication-taking videos were recorded to verify medication adherence, and weekly safety evaluations were also implemented.
NAC utility was evaluated by comparing outcomes between the treatment and control groups while adjusting for baseline drinking, sex, and age. Researchers also conducted exploratory analyses examining whether treatment efficacy differed by sex, age, baseline severity of alcohol use disorder and cannabis use disorder, and baseline psychiatric comorbidity. Longitudinal models were also estimated to assess changes in alcohol use over the treatment period.
The 126 participants ranged in age from 15 to 25 years, with an average age of 21 years. Most of the sample was female (61.9%) and White (88.1%). At baseline, 34.9% of participants met criteria for a mild alcohol use disorder, whereas 33.3% and 31.7% met criteria for moderate or severe alcohol use disorder, respectively. On average, participants reported 19.3 drinking days and 4.9 drinks per drinking day in the 60 days prior to the screening assessment. Study retention and medication adherence were not significantly different between the groups.
There were no overall differences in alcohol use between the NAC and placebo groups
The total number of standard drinks consumed during the final 4 weeks of treatment did not differ between the treatment and control groups (see graph below), and there were also no differences between groups in the total number of drinking days, heavy drinking days, or drinks per drinking day during the same period. Similarly, no significant differences were observed between groups at the 12-week and 26-week follow-ups. Longitudinal changes in alcohol use over the full treatment period also did not differ between groups.
NAC reduced alcohol use in select subgroups of youth
Exploratory analyses indicated that the effects of NAC on alcohol consumption varied by baseline alcohol use disorder severity and sex. Youth with moderate or severe alcohol use disorder who were receiving NAC consumed fewer total drinks during the final 4 weeks of treatment relative to those receiving placebo (see graph below), whereas a significant reduction was not observed in those with mild alcohol use disorder. Treatment effects on the total average number of weekly drinks varied by sex, with a small reduction among females but a small increase among males, though the effect for females was still nonsignificant. None of these moderated effects extended to the alcohol use frequency outcomes.
Overall, N-acetylcysteine (NAC) did not reduce alcohol consumption or frequency of use at any time point compared with placebo. Exploratory analyses revealed that youth with moderate or severe alcohol use disorder who received NAC consumed fewer total drinks during the final 4 weeks of treatment than those receiving placebo, although this moderating effect did not extend to total drinking days or heavy drinking days. The analyses also indicated that the treatment effect on total average number of weekly drinks differed by sex, with a slight reduction in females and a slight increase in males. However, because the within-sex differences in NAC and placebo were small and not significant, this finding should be interpreted with caution.
Although NAC did not demonstrate beneficial effects on alcohol use across all participants, exploratory analyses suggest it could be a more useful adjunctive treatment for certain subgroups of youth (those with moderate or severe alcohol use disorder, females). This highlights the inherent variability of substance use disorder treatment effects and aligns with the increasing recognition that treatments are not one-size-fits-all. Future research should continue to investigate how baseline clinical characteristics and demographics influence treatment utility, with the goal of informing clinical decision-making by identifying youth most likely to benefit from NAC.
The moderated effects of NAC were limited to reductions in the total amount of alcohol consumed, with no evidence of improvements in alcohol use frequency. This aligns with findings from prior trials, which found larger effects of NAC on alcohol use intensity rather than alcohol use frequency. These more favorable consumption outcomes may make NAC more relevant for adolescents and young adults because they typically drink less frequently than adults yet consume larger quantities when they drink. This also suggests that NAC could be a well-suited adjunctive treatment for youth with histories of binge drinking or alcohol-related toxicity. It is unclear why, in the moderate/severe group, NAC reduced total number of drinks, but not heavy drinking days (4+ for females, and 5+ for males). It could be on heavy drinking days, NAC helped reduce number of drinks but not enough to surpass heavy drinking thresholds. This explanation should be tested in future research.
Consistent with prior studies using this dosing schedule, no differences in adverse events were observed between NAC and placebo, further supporting its safety and tolerability. Although overall efficacy was limited, the safety findings nonetheless indicate a favorable (albeit minimal) risk-benefit ratio for its use as an adjunctive treatment.
No overall differences in alcohol use were observed between the N-acetylcysteine (NAC) and placebo groups. However, exploratory analyses revealed that certain subgroups of youth, particularly those with moderate or severe alcohol use disorder, may experience reductions in overall alcohol use – but not alcohol use frequency or heavy drinking days – with NAC. Follow-up studies are needed with you who have severe alcohol use disorder to determine whether NAC may be helpful and recommended clinically.
Squeglia, L. M., Tomko, R. L., Baker, N. L., Kirkland, A. E., McClure, E. A., & Gray, K. M. (in press). A randomized controlled trial of N-acetylcysteine for adolescent and young adult alcohol use disorder. Journal of the American Academy of Child & Adolescent Psychiatry. doi: 10.1016/j.jaac.2025.09.025.
l
Despite the prevalence of alcohol use disorder during adolescence and emerging adulthood, treatments are typically developed for, and tested in, adults. Among the three medications currently approved by the US Food and Drug Administration for treating alcohol use disorder, none are indicated for individuals under 18 years of age. Similarly, the few pharmacotherapy trials conducted with youth who meet alcohol use disorder criteria have exclusively evaluated the effects of naltrexone (sometimes prescribed in a once monthly injections known by the brand name Vivitrol), leaving a significant gap in research on other candidate pharmacotherapies. This is critical given that administering effective treatments during these earlier developmental stages can prevent the progression of alcohol use disorder into later adulthood.
N-acetylcysteine (NAC), an affordable over-the-counter supplement with a well-established safety profile, is a potential pharmacotherapy for treating alcohol use disorder in youth.
Preclinical trials suggest NAC may help restore balance to the brain’s glutamate system, which contributes to drug and alcohol cravings when disrupted by substance use. A trial conducted among adults with alcohol use disorder found that NAC reduced the number of drinks consumed per day but had no effect on other alcohol-related outcomes. Other trials conducted with individuals with cannabis use disorder found that NAC reduced co-occurring alcohol consumption in youth and both alcohol consumption and frequency in adults. Building on these promising findings, this study is the first randomized trial to test the efficacy of NAC in youth with alcohol use disorder.
This randomized controlled trial evaluated the utility of NAC in reducing alcohol use among adolescents and young adults with alcohol use disorder. Individuals aged 13 to 25 years who expressed interest in alcohol use treatment were eligible to participate in the study if they met diagnostic criteria for alcohol use disorder and reported moderate or heavy alcohol use based on established adolescent criteria. Of the 133 individuals assessed for eligibility, 126 were randomized to a NAC treatment group (n = 65) or a placebo control group (n = 61). Randomization was double-blinded (meaning both participants and people doing the assessments did not know which condition people were in), occurred in a 1:1 ratio, and stratified by sex and school enrollment status.
Over an 8-week treatment period, treatment group participants received 2,400 mg of NAC per day, while control group participants received a matched placebo. Participants in both groups also received a weekly brief alcohol intervention that was delivered remotely or in person by a licensed clinician. The 30-minute counseling sessions included motivational interviewing and goal-setting activities. Participants remained in their assigned group for the duration of the study, and both groups were treated concurrently.
The study’s primary outcome was the total number of standard drinks consumed during the final 4 weeks of the treatment period; secondary outcomes included the total number of drinking days, heavy drinking days (4+ for females and 5+ for males in a single day), and drinks per drinking day during the same period. Baseline alcohol use was assessed using structured interviews, and participants reported their alcohol consumption via daily electronic surveys throughout the treatment period. Follow-up assessments were conducted at 12 and 24 weeks post-baseline. Medication-taking videos were recorded to verify medication adherence, and weekly safety evaluations were also implemented.
NAC utility was evaluated by comparing outcomes between the treatment and control groups while adjusting for baseline drinking, sex, and age. Researchers also conducted exploratory analyses examining whether treatment efficacy differed by sex, age, baseline severity of alcohol use disorder and cannabis use disorder, and baseline psychiatric comorbidity. Longitudinal models were also estimated to assess changes in alcohol use over the treatment period.
The 126 participants ranged in age from 15 to 25 years, with an average age of 21 years. Most of the sample was female (61.9%) and White (88.1%). At baseline, 34.9% of participants met criteria for a mild alcohol use disorder, whereas 33.3% and 31.7% met criteria for moderate or severe alcohol use disorder, respectively. On average, participants reported 19.3 drinking days and 4.9 drinks per drinking day in the 60 days prior to the screening assessment. Study retention and medication adherence were not significantly different between the groups.
There were no overall differences in alcohol use between the NAC and placebo groups
The total number of standard drinks consumed during the final 4 weeks of treatment did not differ between the treatment and control groups (see graph below), and there were also no differences between groups in the total number of drinking days, heavy drinking days, or drinks per drinking day during the same period. Similarly, no significant differences were observed between groups at the 12-week and 26-week follow-ups. Longitudinal changes in alcohol use over the full treatment period also did not differ between groups.
NAC reduced alcohol use in select subgroups of youth
Exploratory analyses indicated that the effects of NAC on alcohol consumption varied by baseline alcohol use disorder severity and sex. Youth with moderate or severe alcohol use disorder who were receiving NAC consumed fewer total drinks during the final 4 weeks of treatment relative to those receiving placebo (see graph below), whereas a significant reduction was not observed in those with mild alcohol use disorder. Treatment effects on the total average number of weekly drinks varied by sex, with a small reduction among females but a small increase among males, though the effect for females was still nonsignificant. None of these moderated effects extended to the alcohol use frequency outcomes.
Overall, N-acetylcysteine (NAC) did not reduce alcohol consumption or frequency of use at any time point compared with placebo. Exploratory analyses revealed that youth with moderate or severe alcohol use disorder who received NAC consumed fewer total drinks during the final 4 weeks of treatment than those receiving placebo, although this moderating effect did not extend to total drinking days or heavy drinking days. The analyses also indicated that the treatment effect on total average number of weekly drinks differed by sex, with a slight reduction in females and a slight increase in males. However, because the within-sex differences in NAC and placebo were small and not significant, this finding should be interpreted with caution.
Although NAC did not demonstrate beneficial effects on alcohol use across all participants, exploratory analyses suggest it could be a more useful adjunctive treatment for certain subgroups of youth (those with moderate or severe alcohol use disorder, females). This highlights the inherent variability of substance use disorder treatment effects and aligns with the increasing recognition that treatments are not one-size-fits-all. Future research should continue to investigate how baseline clinical characteristics and demographics influence treatment utility, with the goal of informing clinical decision-making by identifying youth most likely to benefit from NAC.
The moderated effects of NAC were limited to reductions in the total amount of alcohol consumed, with no evidence of improvements in alcohol use frequency. This aligns with findings from prior trials, which found larger effects of NAC on alcohol use intensity rather than alcohol use frequency. These more favorable consumption outcomes may make NAC more relevant for adolescents and young adults because they typically drink less frequently than adults yet consume larger quantities when they drink. This also suggests that NAC could be a well-suited adjunctive treatment for youth with histories of binge drinking or alcohol-related toxicity. It is unclear why, in the moderate/severe group, NAC reduced total number of drinks, but not heavy drinking days (4+ for females, and 5+ for males). It could be on heavy drinking days, NAC helped reduce number of drinks but not enough to surpass heavy drinking thresholds. This explanation should be tested in future research.
Consistent with prior studies using this dosing schedule, no differences in adverse events were observed between NAC and placebo, further supporting its safety and tolerability. Although overall efficacy was limited, the safety findings nonetheless indicate a favorable (albeit minimal) risk-benefit ratio for its use as an adjunctive treatment.
No overall differences in alcohol use were observed between the N-acetylcysteine (NAC) and placebo groups. However, exploratory analyses revealed that certain subgroups of youth, particularly those with moderate or severe alcohol use disorder, may experience reductions in overall alcohol use – but not alcohol use frequency or heavy drinking days – with NAC. Follow-up studies are needed with you who have severe alcohol use disorder to determine whether NAC may be helpful and recommended clinically.
Squeglia, L. M., Tomko, R. L., Baker, N. L., Kirkland, A. E., McClure, E. A., & Gray, K. M. (in press). A randomized controlled trial of N-acetylcysteine for adolescent and young adult alcohol use disorder. Journal of the American Academy of Child & Adolescent Psychiatry. doi: 10.1016/j.jaac.2025.09.025.
l
Despite the prevalence of alcohol use disorder during adolescence and emerging adulthood, treatments are typically developed for, and tested in, adults. Among the three medications currently approved by the US Food and Drug Administration for treating alcohol use disorder, none are indicated for individuals under 18 years of age. Similarly, the few pharmacotherapy trials conducted with youth who meet alcohol use disorder criteria have exclusively evaluated the effects of naltrexone (sometimes prescribed in a once monthly injections known by the brand name Vivitrol), leaving a significant gap in research on other candidate pharmacotherapies. This is critical given that administering effective treatments during these earlier developmental stages can prevent the progression of alcohol use disorder into later adulthood.
N-acetylcysteine (NAC), an affordable over-the-counter supplement with a well-established safety profile, is a potential pharmacotherapy for treating alcohol use disorder in youth.
Preclinical trials suggest NAC may help restore balance to the brain’s glutamate system, which contributes to drug and alcohol cravings when disrupted by substance use. A trial conducted among adults with alcohol use disorder found that NAC reduced the number of drinks consumed per day but had no effect on other alcohol-related outcomes. Other trials conducted with individuals with cannabis use disorder found that NAC reduced co-occurring alcohol consumption in youth and both alcohol consumption and frequency in adults. Building on these promising findings, this study is the first randomized trial to test the efficacy of NAC in youth with alcohol use disorder.
This randomized controlled trial evaluated the utility of NAC in reducing alcohol use among adolescents and young adults with alcohol use disorder. Individuals aged 13 to 25 years who expressed interest in alcohol use treatment were eligible to participate in the study if they met diagnostic criteria for alcohol use disorder and reported moderate or heavy alcohol use based on established adolescent criteria. Of the 133 individuals assessed for eligibility, 126 were randomized to a NAC treatment group (n = 65) or a placebo control group (n = 61). Randomization was double-blinded (meaning both participants and people doing the assessments did not know which condition people were in), occurred in a 1:1 ratio, and stratified by sex and school enrollment status.
Over an 8-week treatment period, treatment group participants received 2,400 mg of NAC per day, while control group participants received a matched placebo. Participants in both groups also received a weekly brief alcohol intervention that was delivered remotely or in person by a licensed clinician. The 30-minute counseling sessions included motivational interviewing and goal-setting activities. Participants remained in their assigned group for the duration of the study, and both groups were treated concurrently.
The study’s primary outcome was the total number of standard drinks consumed during the final 4 weeks of the treatment period; secondary outcomes included the total number of drinking days, heavy drinking days (4+ for females and 5+ for males in a single day), and drinks per drinking day during the same period. Baseline alcohol use was assessed using structured interviews, and participants reported their alcohol consumption via daily electronic surveys throughout the treatment period. Follow-up assessments were conducted at 12 and 24 weeks post-baseline. Medication-taking videos were recorded to verify medication adherence, and weekly safety evaluations were also implemented.
NAC utility was evaluated by comparing outcomes between the treatment and control groups while adjusting for baseline drinking, sex, and age. Researchers also conducted exploratory analyses examining whether treatment efficacy differed by sex, age, baseline severity of alcohol use disorder and cannabis use disorder, and baseline psychiatric comorbidity. Longitudinal models were also estimated to assess changes in alcohol use over the treatment period.
The 126 participants ranged in age from 15 to 25 years, with an average age of 21 years. Most of the sample was female (61.9%) and White (88.1%). At baseline, 34.9% of participants met criteria for a mild alcohol use disorder, whereas 33.3% and 31.7% met criteria for moderate or severe alcohol use disorder, respectively. On average, participants reported 19.3 drinking days and 4.9 drinks per drinking day in the 60 days prior to the screening assessment. Study retention and medication adherence were not significantly different between the groups.
There were no overall differences in alcohol use between the NAC and placebo groups
The total number of standard drinks consumed during the final 4 weeks of treatment did not differ between the treatment and control groups (see graph below), and there were also no differences between groups in the total number of drinking days, heavy drinking days, or drinks per drinking day during the same period. Similarly, no significant differences were observed between groups at the 12-week and 26-week follow-ups. Longitudinal changes in alcohol use over the full treatment period also did not differ between groups.
NAC reduced alcohol use in select subgroups of youth
Exploratory analyses indicated that the effects of NAC on alcohol consumption varied by baseline alcohol use disorder severity and sex. Youth with moderate or severe alcohol use disorder who were receiving NAC consumed fewer total drinks during the final 4 weeks of treatment relative to those receiving placebo (see graph below), whereas a significant reduction was not observed in those with mild alcohol use disorder. Treatment effects on the total average number of weekly drinks varied by sex, with a small reduction among females but a small increase among males, though the effect for females was still nonsignificant. None of these moderated effects extended to the alcohol use frequency outcomes.
Overall, N-acetylcysteine (NAC) did not reduce alcohol consumption or frequency of use at any time point compared with placebo. Exploratory analyses revealed that youth with moderate or severe alcohol use disorder who received NAC consumed fewer total drinks during the final 4 weeks of treatment than those receiving placebo, although this moderating effect did not extend to total drinking days or heavy drinking days. The analyses also indicated that the treatment effect on total average number of weekly drinks differed by sex, with a slight reduction in females and a slight increase in males. However, because the within-sex differences in NAC and placebo were small and not significant, this finding should be interpreted with caution.
Although NAC did not demonstrate beneficial effects on alcohol use across all participants, exploratory analyses suggest it could be a more useful adjunctive treatment for certain subgroups of youth (those with moderate or severe alcohol use disorder, females). This highlights the inherent variability of substance use disorder treatment effects and aligns with the increasing recognition that treatments are not one-size-fits-all. Future research should continue to investigate how baseline clinical characteristics and demographics influence treatment utility, with the goal of informing clinical decision-making by identifying youth most likely to benefit from NAC.
The moderated effects of NAC were limited to reductions in the total amount of alcohol consumed, with no evidence of improvements in alcohol use frequency. This aligns with findings from prior trials, which found larger effects of NAC on alcohol use intensity rather than alcohol use frequency. These more favorable consumption outcomes may make NAC more relevant for adolescents and young adults because they typically drink less frequently than adults yet consume larger quantities when they drink. This also suggests that NAC could be a well-suited adjunctive treatment for youth with histories of binge drinking or alcohol-related toxicity. It is unclear why, in the moderate/severe group, NAC reduced total number of drinks, but not heavy drinking days (4+ for females, and 5+ for males). It could be on heavy drinking days, NAC helped reduce number of drinks but not enough to surpass heavy drinking thresholds. This explanation should be tested in future research.
Consistent with prior studies using this dosing schedule, no differences in adverse events were observed between NAC and placebo, further supporting its safety and tolerability. Although overall efficacy was limited, the safety findings nonetheless indicate a favorable (albeit minimal) risk-benefit ratio for its use as an adjunctive treatment.
No overall differences in alcohol use were observed between the N-acetylcysteine (NAC) and placebo groups. However, exploratory analyses revealed that certain subgroups of youth, particularly those with moderate or severe alcohol use disorder, may experience reductions in overall alcohol use – but not alcohol use frequency or heavy drinking days – with NAC. Follow-up studies are needed with you who have severe alcohol use disorder to determine whether NAC may be helpful and recommended clinically.
Squeglia, L. M., Tomko, R. L., Baker, N. L., Kirkland, A. E., McClure, E. A., & Gray, K. M. (in press). A randomized controlled trial of N-acetylcysteine for adolescent and young adult alcohol use disorder. Journal of the American Academy of Child & Adolescent Psychiatry. doi: 10.1016/j.jaac.2025.09.025.
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