NAC for OCD, Hair-Pulling & Depression: Independent Evidence

Table of contents

• Evidence summary
• What NAC is, and its legal status
• How it works
• What works and what does not
• Benefits by claim
• Risks and all side effects
• All interactions
• Who should avoid NAC
• Doses studied and product quality
• Follow the money: who makes it and who funded the evidence
• Related research
• Frequently asked questions
• Sources and funding notes

Evidence summary

Independent evidence and credibility scorecard

Independence tiers: 1 = regulator or government body; 2 = academic or Cochrane team with no declared commercial funding for the work; 3 = independent authors with minor declared industry ties, investigator patents, or industry-supplied study products; 4 = manufacturer, seller or trade body. Credibility runs from A (highest) to D.

Most sources come from the US and Australia. Much of the Australian psychiatric NAC research comes from one research network in Geelong and Melbourne. Most positive OCD trials come from Iran. When trials cluster like this, their results should be read as linked rather than as fully separate replications.

What NAC is, and its legal status

N-acetylcysteine (also called acetylcysteine, N-acetyl-L-cysteine or NAC) is a modified form of the amino acid cysteine. Doctors have used it for decades in two main ways. It thins mucus in chest disease, and given into a vein it is the standard antidote to paracetamol (acetaminophen) overdose. The Italian company Zambon discovered its mucus-thinning effect in 1960 and launched the brand Fluimucil in 1965 (Zambon, 2025). In the US it was first approved as a new drug in 1963, the date reported as relied on in FDA's 2020 warning letters (SupplySide, 2024).

No regulator has approved NAC for OCD, hair-pulling, skin-picking, depression, bipolar disorder or addiction. Any psychiatric use is "off-label" (outside the licence) or happens through supplement products.

Legal status by country

• United States: US law excludes an ingredient from the definition of a dietary supplement if it was approved as a new drug before it was sold as a supplement. FDA applied this rule to NAC in 2020. It confirmed the position on 31 March 2022, when it denied petitions from two industry groups, the Council for Responsible Nutrition and the Natural Products Association (FDA constituent update). In August 2022 FDA finalised a policy of "enforcement discretion". In practice, FDA does not take action against NAC products labelled as supplements, provided they would otherwise be lawful (FDA guidance). FDA's Spring 2025 regulatory agenda listed a proposed rule that would formally allow NAC in supplements, with its target date moved to January 2026 (Covington, 2025). The Natural Products Association said no proposed rule had been published as of December 2025 (NPA). When we searched the Federal Register on 7 October 2026, FDA had published only its 2022 draft and final NAC guidance notices and no proposed rule (Federal Register search). So, as of October 2026, NAC supplements still rely on FDA's enforcement-discretion policy, not on a rule.
• United Kingdom: acetylcysteine 600 mg effervescent tablets are licensed medicines for thinning mucus, at a label dose of 600 mg once daily for adults (Acepiro SmPC). We did not find an official UK statement on NAC sold as a food supplement.
• Elsewhere: Zambon describes Fluimucil as available in several international markets, including a 2025 approval of the intravenous form in China (Zambon). We did not verify supplement rules in the EU, Australia or Canada.

How it works

The leading theory involves glutamate, the brain's main "go" chemical messenger. Once in the body, NAC is converted to cysteine. Cysteine drives a pump on brain support cells called the cystine–glutamate antiporter. This pump swaps cystine for glutamate outside nerve cells, and the result is thought to calm excess glutamate release in reward and habit circuits. NAC is also a building block for glutathione, the body's main internal antioxidant, and in laboratory and animal studies it lowers some markers of inflammation (Dean, Giorlando & Berk 2011).

What is proven in humans and what is not: taking NAC by mouth raises cysteine and glutathione in the blood. The glutamate-pump effect and the brain antioxidant effect come mainly from rodent studies (Dean 2011). That review was written by the same Australian group that later ran several of the trials; we could not open its funding statement. A small 10-day crossover brain-scan study in 31 teenagers who drank heavily found no change in brain glutamate, GABA or glutathione on NAC (1,200 mg twice daily) compared with placebo (Kirkland 2023). The mechanism is plausible, but it has not been shown to explain any clinical benefit in people.

What works and what does not

Benefits by claim

Does NAC work for trichotillomania (hair-pulling)?

This is where NAC has its best result. In 2009, a University of Minnesota team randomised 50 adults (45 women) to NAC at 1,200–2,400 mg a day or to placebo for 12 weeks. Hair-pulling fell significantly more on NAC on two scales: the Massachusetts General Hospital Hair Pulling Scale (P<.001) and the Psychiatric Institute Trichotillomania Scale (P=.001). In all, 56% of the NAC group were rated much or very much improved, compared with 16% on placebo. Benefit first appeared at week 9 (Grant 2009). The university's press release said the medical school funded the study (ScienceDaily).

The 2021 Cochrane review of medicines for hair-pulling expressed this as a risk ratio of 3.5 (95% CI 1.34 to 9.17). A risk ratio is how many times more likely a good response was on NAC than on placebo. Cochrane rated the evidence moderate certainty, the highest rating it gave any medicine in the review, but it rests on a single trial (Hoffman 2021; PMC record). The 10 adult trials in the review averaged only 29 participants each.

Children are different. A Yale trial gave NAC or placebo, alongside other care, to 39 children and teenagers aged 8–17 for 12 weeks. There was no difference on any measure: 25% of the NAC group responded, compared with 21% on placebo. The authors concluded that children should be referred for behavioural therapy before any medicine is tried (Bloch 2013). For the wider treatment picture, including habit-reversal therapy, see our trichotillomania guide.

Does NAC help skin-picking (excoriation disorder)?

The same lead investigator, Jon Grant, ran a 12-week trial in 66 adults (89% women) at the Universities of Minnesota and Chicago, using 1,200–3,000 mg a day. Skin-picking was measured on a 40-point version of the Yale-Brown scale. Scores fell from 18.9 to 11.5 on NAC and from 17.9 to 14.1 on placebo, a just-significant difference (P=.048). Among the 53 people who finished, 47% on NAC were much or very much improved, compared with 19% on placebo. There was no difference in day-to-day functioning (Grant 2016). The trial is registered as NCT01063348, with the University of Chicago as sponsor. Only completers were included in the responder figure, and no independent team has repeated the trial. See our excoriation disorder guide for therapy options.

Does NAC work for OCD? (NAC for OCD)

This is the claim people search for most, and the evidence divides sharply by trial size and setting. The trials are listed below.

• Iran, 2012: 48 adults whose OCD had not responded to an SSRI. NAC up to 2,400 mg for 12 weeks. 52.6% full responders on NAC vs 15% on placebo (Afshar 2012).
• Iran, 2016: 44 adults starting fluvoxamine 200 mg plus NAC 2,000 mg or placebo for 10 weeks. NAC was statistically better over time (Paydary 2016). Europe PMC lists Tehran University of Medical Sciences as funder.
• Iran, 2017: 34 children and teenagers taking citalopram plus NAC or placebo for 10 weeks. Scores were lower on NAC by the end (Ghanizadeh 2017).
• Australia, 2015: 44 adults on NAC 3,000 mg for 16 weeks. No significant difference on the total score (P=.39). Responders were 20% on NAC and 27% on placebo. Heartburn was more common on NAC (Sarris 2015).
• Brazil, 2017: 40 adults with treatment-resistant OCD, NAC 3,000 mg for 16 weeks. Scores fell 4.3 points on NAC and 3.0 on placebo, with no significant difference (P=.92). Anxiety improved more on NAC (Costa 2017). The registry lists the University of São Paulo as sponsor and the state research foundation FAPESP as collaborator (NCT01555970).
• Australia, 2022 (phase III): 98 adults at several sites on 2–4 g a day for 20 weeks. There was no benefit on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS): the mean difference was 0.53 points favouring placebo (95% compatibility interval −2.18 to 3.23). There was also no benefit for anxiety, depression, quality of life or functioning (Sarris 2022).

Two meta-analyses (studies that pool trial results) reach different conclusions. A Japanese team pooled 10 NAC trials covering OCD, hair-pulling and skin-picking (n=453). It found a standardised mean difference of −0.77 (95% CI −1.26 to −0.29). That would be a large effect, but the trials disagreed with each other a great deal (I²=83%), and NAC did not significantly raise response rates (P=.09) (Kishi 2022). An Iranian meta-analysis of six adult OCD trials (n=195) found a 2.95-point Y-BOCS benefit at 5–8 weeks (95% CI −5.87 to −0.04, P=.05). It found no significant benefit at four weeks or less, nor at 12 weeks or more (Eghdami 2024). A benefit that appears at 8 weeks and is gone by 12 weeks is not a reliable treatment effect.

Our reading is that the larger and longer trials are negative. The positive pooled results depend on small, short trials. NAC should not take the place of exposure and response prevention therapy or an SSRI. See our OCD guide, and our reviews of fluvoxamine and clomipramine.

Does NAC help bipolar depression?

The idea came from Michael Berk's group in Geelong, Australia. In 2008 they randomised 75 people with bipolar disorder who still had depressive symptoms despite usual treatment. Half took NAC 1 g twice a day and half took placebo, for 24 weeks. On the 60-point Montgomery–Åsberg Depression Rating Scale (MADRS), NAC was 8.05 points better (95% CI −13.16 to −2.95). The benefit disappeared after the four-week washout, and NAC did not delay new mood episodes (Berk 2008).

Two follow-up trials were negative. In a maintenance trial, 149 people took NAC openly for eight weeks and were then randomised. There was no difference in relapse or symptoms (Berk 2012). A three-arm 16-week trial in 181 people compared NAC 2,000 mg, NAC plus a mix of other nutrients, and placebo. None of the arms differed on any clinical measure at the primary endpoint, and stomach symptoms were more common on NAC (Berk 2019). A 2018 meta-analysis found no significant effect of NAC on depressive or manic symptoms in bipolar disorder (Zheng 2018). A Danish trial of 3 g a day was registered (NACOS protocol); we did not find its results. See our bipolar depression guide.

Does NAC help depression?

The largest trial in major depression added NAC or placebo to usual treatment in 252 people for 12 weeks. It missed its primary outcome: MADRS scores did not separate at week 12 (P=.265). Some secondary measures favoured NAC at week 16, and so did a subgroup with more severe depression. Stomach and muscle or joint side effects were more common on NAC. The authors called the support "only limited" (Berk 2014).

Pooled results suggest a small effect. A 2016 meta-analysis of 5 trials (n=574) found a standardised mean difference of 0.37 (95% CI 0.19 to 0.55). Its five authors include Michael Berk, who led several of the pooled trials (Fernandes 2016). A 2024 update by an independent Taiwanese team pooled 12 trials (n=904) and found a smaller effect: −0.24 (95% CI −0.44 to −0.05), with moderate heterogeneity (I²=45%) (Peng 2024). In plain terms, an effect of about 0.24 is small. Most people would not notice it, and the lower confidence limit is close to zero. See our guides to major depressive disorder and treatment-resistant depression.

Does NAC help addiction?

NAC for addiction has followed a familiar pattern: an early positive trial, then larger negative ones. In 2012, an NIH-funded trial gave 116 cannabis-dependent 15–21-year-olds NAC 1,200 mg twice daily or placebo. Everyone also received contingency management, a programme of rewards for negative urine tests. Those on NAC had more than twice the odds of a negative test (OR 2.4, 95% CI 1.1 to 5.2) (Gray 2012).

A six-site NIH trial in 302 adults then found no effect: 22.3% of urine tests were negative on NAC and 22.4% on placebo (OR 1.00, 0.63 to 1.59) (Gray 2017). A 2025 trial in 192 young people, without the reward programme, also found no effect (RR 0.93, 0.53 to 1.64). Stomach side effects were more common on NAC (Gray 2025). The 2025 Cochrane review found that NAC probably does not make abstinence more likely (RR 1.17, 95% CI 0.73 to 1.88; 2 studies, 270 people; moderate certainty) (Spiga 2025).

For craving across alcohol, tobacco and other drugs, a 2024 meta-analysis of 9 trials (n=623) found no significant effect (SMD 0.189, −0.015 to 0.393). It also found signs of publication bias, which means positive trials may be over-represented in the literature (Winterlind 2024).

Risks and all side effects

Common side effects in psychiatric trials

Stomach and bowel effects are the most consistent finding. Abdominal pain affected 60% on NAC vs 13.3% on placebo in the Brazilian OCD trial (Costa 2017). Heartburn was more frequent in the first Australian OCD trial (Sarris 2015). Gastrointestinal events affected 63 of 98 young people on NAC vs 37 of 94 on placebo in the 2025 cannabis trial (Gray 2025). Gastrointestinal and musculoskeletal events were more common in the major depression trial (Berk 2014). Serious adverse events were not more frequent than on placebo in the Cochrane cannabis analysis (RR 0.16, 0.02 to 1.33; 418 people) (Cochrane 2025). One meta-analysis found minor adverse events slightly more likely on NAC (OR 1.61, 1.01 to 2.59) (Fernandes 2016).

Other label side effects

The UK label also lists headache, tinnitus, fast heart rate, low blood pressure, bleeding, mouth inflammation, nausea, vomiting, diarrhoea, indigestion, itching, rash, hives, fever and facial swelling. Most are uncommon or rare. The label also warns that prolonged use should be avoided in people with histamine intolerance, because NAC affects how the body breaks down histamine. Symptoms can include headache, runny nose and itching (SmPC).

Smell, taste and blinding

NAC has a strong sulphur smell. Trial teams went to some lengths to stop participants guessing which capsule they had. The paediatric trichotillomania team coated capsules with peppermint oil (Bloch 2013). The Australian bipolar team dusted placebo capsules with tiny amounts of NAC (Berk 2012). If the smell gave the treatment away, positive trials could look better than they really are.

All interactions

The UK label lists the following interactions for oral acetylcysteine (Acepiro SmPC):

• Nitroglycerin (glyceryl trinitrate): NAC may strengthen its blood-vessel-widening effect, so blood pressure should be watched for drops.
• Some antibiotics: tetracycline, aminoglycosides and penicillins are inactivated when mixed directly with NAC in the laboratory. The label advises taking oral antibiotics at least two hours apart.
• Activated charcoal: may reduce NAC's effect.
• Cough suppressants: not to be taken at the same time when NAC is used to loosen mucus.
• Heavy metal salts: NAC may bind them, so take them at different times of day.
• Laboratory tests: NAC may interfere with salicylate tests and urine ketone tests.

In the psychiatric trials, NAC was added to SSRIs, mood stabilisers, antipsychotics and other usual treatments without a signal of serious interaction (Berk 2008; Sarris 2022). Most of these trials had fewer than 200 participants, so rare interactions could have been missed.

Who should avoid NAC

• People with asthma or past bronchospasm: use only with caution, and stop if wheeze develops (SmPC).
• People with a history of peptic ulcer: the label advises caution.
• People with histamine intolerance: avoid prolonged use.
• Liver or kidney impairment: NAC may build up and cause more side effects.
• Pregnancy and breastfeeding: human data are limited, and the label advises use only after a strict risk–benefit assessment.
• Children: the 600 mg product is not for children or teenagers, and acetylcysteine is contraindicated under age 2. NAC did not help children with hair-pulling (Bloch 2013).
• Anyone with a known allergy to acetylcysteine.
• People with bipolar disorder: trials did not show NAC causing mania (Zheng 2018). Even so, any new treatment should be discussed with the person's psychiatrist, and NAC is not a mood stabiliser.

Doses studied and product quality

These are doses used in trials, not recommendations.

• Trichotillomania: 1,200–2,400 mg a day for 12 weeks, with benefit first seen at week 9 (Grant 2009).
• Skin-picking: 1,200–3,000 mg a day for 12 weeks (Grant 2016).
• OCD: 2,000–4,000 mg a day for 10–20 weeks (Paydary 2016; Sarris 2022).
• Bipolar and major depression: 1 g twice daily (Berk 2008; Berk 2019).
• Cannabis use disorder: 1,200 mg twice daily (Gray 2017).
• UK licensed label dose (mucolytic use only): 600 mg once daily (SmPC).

Product quality

Trial capsules were made to pharmaceutical standards. The Australian bipolar trial used NAC from Zambon with 99.8% purity confirmed by chromatography (Berk 2012). Supplements sold under the FDA's enforcement-discretion policy are not checked by FDA before sale. FDA's guidance concerns legal status, not product testing (FDA). We found no published independent test of NAC supplement content that we could verify for this article. For how brands disclose lab results in general, see our COA transparency audit.

Follow the money: who makes it and who funded the evidence

Who makes and sells it

Pharmaceutical NAC is a long-established generic medicine. Zambon, a family-rooted Italian pharmaceutical company based in Bresso near Milan, discovered its mucus-thinning use and still sells Fluimucil internationally (Zambon). In the UK, licensed 600 mg tablets include Acepiro from Stirling Anglian Pharmaceuticals of Glasgow (SmPC). Supplement NAC is sold by many brands. We found no citable market-size figure. The US supplement trade bodies, the Council for Responsible Nutrition and the Natural Products Association, petitioned FDA to keep NAC on sale as a supplement (FDA).

Who funded the trials

• Trichotillomania and skin-picking: the 2009 adult trial was funded by the University of Minnesota Medical School (press release). The 2016 skin-picking trial lists the University of Chicago as sponsor (registry); we could not see its full funding statement. The negative paediatric trial was funded by NIH grants (Bloch 2013).
• OCD: the Iranian trials came from university medical schools, and Europe PMC lists Tehran University of Medical Sciences for Paydary 2016. The Brazilian trial was sponsored by the University of São Paulo with FAPESP (registry). The 2022 Australian phase III trial's grant record lists NHMRC, Stanley Medical Research Institute, Deakin University and drug makers Servier, H. Lundbeck, Pfizer, Cilag, Eli Lilly, GlaxoSmithKline and Janssen. We did not see its own funding statement.
• Bipolar and depression: Europe PMC lists the Stanley Medical Research Institute, the NHMRC, the Australian Research Council and CSIRO as funders of the 2008 trial (Europe PMC). The 2012 maintenance paper thanks the Stanley Medical Research Institute and NHMRC. It discloses that two investigators, including lead author Michael Berk, were "co-inventors on two provisional patents" for psychiatric uses of NAC, assigned to the Mental Health Research Institute. Berk also declared grants, speaker fees or consultancy from many antidepressant and antipsychotic makers (Berk 2012). The 2019 trial was funded by the CRC for Mental Health and an NHMRC project grant, and the funders had no role in the analysis. Study capsules and placebos were supplied by Nutrition Care, Catalent and BioCeuticals, all in Australia (Berk 2019).
• Addiction: all three Gray cannabis trials were funded by the US National Institute on Drug Abuse. The 2012 trial's record lists NIDA and NCRR (NIH) grants (Gray 2012), and the 2017 trial ran through NIDA's Clinical Trials Network (Gray 2017). The 2025 paper's record lists NIH grants (NIDA, NIAAA and NCATS) and no disclosure text, so author conflicts first drafted could not be confirmed and are omitted (Gray 2025).

Unlike many supplements, NAC's psychiatric evidence was not built on trials run by a seller. The interest that most needs disclosing is intellectual and patent-based, not sales-based. Even so, the patent-linked group published several negative trials.

Documented integrity events

• 2020: FDA sent warning letters to companies selling NAC hangover products, saying NAC could not lawfully be marketed as a supplement (SupplySide, 2024).
• May 2021: Amazon announced plans to remove NAC supplements from its platform (SupplySide).
• 2021–2022: the Natural Products Association sued FDA. It dropped the case in November 2022 after FDA's enforcement-discretion guidance (SupplySide).
• 31 March 2022: FDA denied the CRN and NPA petitions but kept the NPA's rulemaking request under review (FDA).
• August 2022: FDA's final enforcement-discretion guidance (FDA).
• 2024–2025: FDA's regulatory agendas listed a proposed rule to allow NAC in supplements. This would be the first rule of its kind under the 1994 supplement law (SupplySide; Covington).

We found no recalls or contamination findings for NAC supplements that we could verify.

Related research

For wider, evidence-graded context, see these Pure City Research guides:

• Trichotillomania (hair-pulling disorder): assessment, treatment evidence and safety
• Excoriation (skin-picking) disorder
• Obsessive-compulsive disorder
• Body dysmorphic disorder
• Fluvoxamine: OCD and depression evidence
• Clomipramine for OCD
• Bipolar depression
• Major depressive disorder
• Treatment-resistant depression
• Myo-inositol
• Supplements for stress, anxiety and depression: the evidence
• The COA transparency audit

Frequently asked questions

Sources and funding notes

What we could not verify: the full funding statements of the 2016 skin-picking trial, the 2015 Australian OCD trial, the 2014 major-depression trial (Europe PMC lists a "Medical Research Council" without detail), the Iranian OCD trials other than Paydary 2016, the Zheng 2018 meta-analysis, the 2011 Dean mechanisms review, and the author declarations in the 2021 Cochrane hair-pulling review (its funder, the Wellcome Trust, is now confirmed). Journal pages were paywalled or blocked, so we did not cite them for funding. We did not open the regulations.gov petition files or the 2020 FDA warning letters themselves, and we rely on trade-press reports for the warning letters, the Amazon removal and the NPA lawsuit. We could not open FDA's regulatory agenda entry, so we cannot say what target date FDA now lists for its proposed NAC rule; a Federal Register search on 7 October 2026 found no proposed rule. The results of the Danish NACOS bipolar trial and any independent lab testing of NAC supplements were not found. We found no citable NAC market-size figure. Not re-checked in this pass: the 2012 Berk patent disclosure, the 2019 capsule suppliers, the 2016 Fernandes author list, the Cochrane 2021 author declarations, the Zambon 1960 and 1965 dates, the 2025 FDA agenda date, and the SmPC frequency table for rare reactions. PubMed was rate-limited, so several records were checked through Europe PMC instead.

1. FDA: Policy Regarding N-acetyl-L-cysteine, guidance for industry (August 2022) — US regulator.
2. FDA: response to two citizen petitions on NAC (31 March 2022) — US regulator.
3. Acepiro 600 mg effervescent tablets SmPC (revised May 2025) — Stirling Anglian Pharmaceuticals; text approved under a UK marketing authorisation.
4. Hoffman J et al. Pharmacotherapy for trichotillomania. Cochrane 2021 (PMC) — systematic review; author interests declared (one author consults for Promentis and Ieso Digital Health).
5. Grant JE, Odlaug BL, Kim SW. NAC in trichotillomania. Arch Gen Psychiatry 2009; NCT00354770; University of Minnesota press release — RCT; University of Minnesota Medical School.
6. Grant JE et al. NAC in excoriation disorder. JAMA Psychiatry 2016; NCT01063348 — RCT; sponsor University of Chicago; funding statement not verified.
7. Bloch MH et al. NAC in paediatric trichotillomania. JAACAP 2013 (full text) — RCT; US NIH and Trichotillomania Learning Center.
8. Afshar H et al. NAC add-on in refractory OCD. J Clin Psychopharmacol 2012 — RCT, Iran; funding not verified.
9. Paydary K et al. NAC augmentation for OCD. J Clin Pharm Ther 2016 — RCT, Iran; Tehran University of Medical Sciences (Europe PMC).
10. Ghanizadeh A et al. NAC augmentation in paediatric OCD. Iran J Psychiatry 2017 — RCT, Iran; funding not verified.
11. Sarris J et al. NAC in OCD, 16-week RCT. CNS Drugs 2015 — RCT, Australia; funding not verified.
12. Costa DLC et al. NAC for treatment-resistant OCD. J Clin Psychiatry 2017; NCT01555970 — RCT, Brazil; University of São Paulo with FAPESP.
13. Sarris J et al. NAC augmentation in OCD, phase III. Prog Neuropsychopharmacol Biol Psychiatry 2022 — RCT, Australia; grant record lists NHMRC, Stanley, Deakin and drug makers (Servier, Lundbeck, Pfizer, Cilag, Lilly, GSK, Janssen).
14. Kishi T et al. Mitochondrial modulators for OCD and related disorders. Transl Psychiatry 2022 — meta-analysis, Japan; authors' pharma speaker fees declared.
15. Eghdami S et al. NAC augmentation in adult OCD. Front Psychiatry 2024 — meta-analysis; Iran University of Medical Sciences grant.
16. Berk M et al. NAC for depressive symptoms in bipolar disorder. Biol Psychiatry 2008; Europe PMC funder record — RCT, Australia; Stanley Medical Research Institute, NHMRC and others.
17. Berk M et al. Maintenance NAC for bipolar disorder. BMC Med 2012 (full text) — RCT; Stanley Medical Research Institute and NHMRC; investigator patent disclosure.
18. Berk M et al. Mitochondrial agents, NAC and placebo for bipolar depression. BMC Med 2019 (full text) — RCT; CRC for Mental Health and NHMRC; capsules from Nutrition Care, Catalent, BioCeuticals.
19. Ellegaard PK et al. NACOS study protocol. Int J Bipolar Disord 2018 — trial protocol, Denmark.
20. Zheng W et al. NAC for major mental disorders. Acta Psychiatr Scand 2018 — meta-analysis, China; funding not verified.
21. Berk M et al. Adjunctive NAC in major depressive disorder. J Clin Psychiatry 2014 — RCT, Australia; funding not verified.
22. Fernandes BS et al. NAC in depressive symptoms and functionality. J Clin Psychiatry 2016 — meta-analysis; co-authored by the lead investigator of several pooled trials.
23. Peng TR et al. NAC for depression: updated meta-analysis. Gen Hosp Psychiatry 2024 — meta-analysis, Taiwan; Buddhist Tzu Chi Medical Foundation and Taipei Tzu Chi Hospital grants; no competing-interest statement in the record.
24. Gray KM et al. NAC in cannabis-dependent adolescents. Am J Psychiatry 2012 (full text) — RCT; NIDA and NCRR (NIH) grants.
25. Gray KM et al. NAC for cannabis use disorder in adults. Drug Alcohol Depend 2017 (full text) — RCT; NIDA Clinical Trials Network.
26. Gray KM et al. NAC for youth cannabis use disorder. Neuropsychopharmacology 2025 (full text) — RCT; NIH grants; author disclosures not in the record we read.
27. Spiga F et al. Pharmacotherapies for cannabis use disorder. Cochrane 2025 — systematic review; author interests declared.
28. Winterlind EL et al. NAC for substance use cravings. Addict Biol 2024 — meta-analysis; NIAAA and US Department of Defense.
29. Dean O, Giorlando F, Berk M. NAC in psychiatry: mechanisms. J Psychiatry Neurosci 2011 — narrative review; funding statement not verified (PDF only).
30. Kirkland AE et al. NAC and neurometabolites in adolescents who drink heavily. Neuropsychopharmacology 2023 — brain-imaging crossover RCT, US; NIH (NIAAA and NIDA) grants per Europe PMC.
31. SupplySide Supplement Journal: FDA is exploring rulemaking for NAC supplements (July 2024) — trade press.
32. Covington & Burling: Unified Agenda implications (September 2025) — law-firm analysis.
33. Natural Products Association: NAC — supplement trade body; interested party.
34. Zambon press release: intravenous Fluimucil in China (June 2025) — manufacturer.

Educational research reviewed 6 October 2026. This article is not medical advice; talk to a qualified clinician or pharmacist before starting, stopping or combining treatments.