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AOD-9604 Peptide: Fat-Loss Hype vs the Record

Creator: Elena Marsh, Health Writer
Published: 2026-08-14

Six placebo-controlled trials in 893 obese adults — capped by a 536-subject study that missed its endpoints — ended AOD-9604's drug development in 2007.

Elena Marsh, Health Writer August 14, 2026 14 min read

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The short version

AOD-9604 (short for "Anti-Obesity Drug-9604") is a synthetic 16-amino-acid fragment of human growth hormone — residues 177–191 plus an added N-terminal tyrosine — designed in the 1990s to isolate hGH's fat-metabolism activity without its growth, IGF-1, or blood-sugar effects.
Six randomized, double-blind, placebo-controlled trials (2001–2006) enrolled 893 obese adults using oral and intravenous dosing; the most favorable reported result was about 1.8–2 kg more weight loss than placebo over 12 weeks.
A 536-subject, 24-week trial failed to show statistically significant weight loss versus placebo, and development was terminated in 2007; no New Drug Application was ever submitted.
In the trials, tolerability was indistinguishable from placebo, with no anti-drug antibodies and no changes in IGF-1 or glucose tolerance — but there are no human data beyond 24 weeks and none at all for the subcutaneous injections sold online.
AOD-9604 is not FDA-approved as a drug, and on December 4, 2024 an FDA advisory committee voted against allowing it in 503A pharmacy compounding; it holds only self-affirmed GRAS status — not an FDA review — for oral food use at about 1 mg per day.
AOD-9604 is prohibited in sport under WADA category S2 and is detectable in urine at concentrations as low as 50 pg/mL.

The AOD-9604 peptide has one of the loudest reputations in the online weight-loss world, where it is sold as a "fat-burning peptide" descended from human growth hormone. The clinical record is more specific and far less flattering. Between 2001 and 2006, six randomized, placebo-controlled trials gave AOD-9604 to 893 obese adults, by mouth or intravenously. The best reported outcome was roughly 1.8–2 kg more weight loss than placebo over 12 weeks. The largest trial — 536 subjects over 24 weeks — missed its efficacy endpoints, and the developer terminated the program in 2007. The numbers, not the marketing, are the story worth knowing before you consider it.

What is the AOD-9604 peptide?

AOD-9604 is a synthetic peptide fragment of human growth hormone, built from the hormone's C-terminal region — amino acids 177–191 — with an extra tyrosine added at the N-terminus for stability, making 16 amino acids in all (a hexadecapeptide). The name is short for "Anti-Obesity Drug-9604," which states its intended purpose plainly.

The science began in the 1990s at Monash University in Australia, in Frank Ng's biochemistry group, with drug development carried forward by Metabolic Pharmaceuticals of Melbourne. The rationale was straightforward: full human growth hormone stimulates fat breakdown, but treating obesity with the whole hormone brings its well-known baggage — joint pain, fluid retention, insulin resistance and increased diabetes risk, carpal tunnel symptoms, acromegaly risk with prolonged excess, and the cancer concern attached to elevated IGF-1. The design goal was to clip out the region responsible for fat metabolism and leave the rest of the hormone's activity behind.

One naming note that trips people up: AOD-9604 is the development name for what vendors also sell as "modified hGH fragment 176-191." They are the same molecule — the "176–191" count simply includes the added tyrosine at position one. AOD-9604 is classified as a synthetic peptide fragment, not a hormone.

How AOD-9604 was designed to work

In animal and cell studies, AOD-9604 stimulates lipolysis — the breakdown of stored triglycerides in fat cells — inhibits lipogenesis (the formation of new fat), and increases fat oxidation, all without binding the growth hormone receptor or raising IGF-1. That is the design brief, and the preclinical data largely met it. The human data, as the next section shows, diverged.

The preclinical trail is real and spans three decades. In 1993, Wu and Ng showed the C-terminal 177–191 sequence of hGH had antilipogenic activity — it suppressed new fat formation. In 1994, chronic treatment with the synthetic 177–191 peptide reduced cumulative weight gain and adipose tissue mass in obese mice. In 2001, Heffernan and colleagues reported that 14 days of treatment with hGH or the modified fragment increased fat oxidation and plasma glycerol in obese (ob/ob) mice and produced weight loss — notably without the hyperglycemia or reduced insulin secretion the full hormone caused. The fragment also inhibits the differentiation and proliferation of pre-adipocytes in vitro.

The most interesting mechanistic finding involves the beta-3 adrenergic receptor, a signaling protein on fat cells. In adipose tissue, beta-3 activation raises intracellular cyclic AMP, which activates protein kinase A and drives hormone-sensitive lipase to break down triglycerides — the textbook lipolysis cascade. A 2001 study in Endocrinology found that both hGH and AOD-9604 upregulate beta-3 receptor RNA expression in the fat tissue of obese mice, restoring the repressed levels seen in obesity back toward lean-mouse levels. But the same study complicated the story: in mice genetically lacking the beta-3 receptor, chronic treatment failed to produce the weight-loss and lipolysis changes seen in normal mice — yet a single acute dose still increased energy expenditure and fat oxidation in those knockout animals. The authors concluded that the lipolytic actions of hGH and AOD-9604 are not mediated directly through the beta-3 receptor, though the increased receptor expression may contribute to enhanced lipolytic sensitivity. Marketing copy that calls the beta-3 pathway "essential" or "proven" is overreading that paper.

Two other design features held up in testing. AOD-9604 does not compete for binding at the hGH receptor and does not trigger cell proliferation through it, shown in receptor-transfected cell assays. And in human trials it produced no change in serum IGF-1 and no negative effect on glucose tolerance in oral glucose tolerance testing — no insulin-resistance signal. The researchers' own framing is worth carrying: hGH behaves in some ways as a pro-hormone, and fragments of it can act in ways novel to traditional hGH-stimulated pathways.

The caveat over all of this: the proposed mechanisms rest primarily on animal and in vitro studies. Claims that AOD-9604 raises metabolic rate in humans have no supporting human data — the energy-expenditure findings are acute results in mice.

What six clinical trials found

The human program was substantial, well-controlled — and unsuccessful. Six randomized, double-blind, placebo-controlled trials run primarily in Australia between 2001 and 2006 enrolled 893 otherwise-healthy, clinically obese adults. Weight loss differences from placebo were small at best, no consistent dose–response emerged, and the largest trial missed statistical significance, ending development in 2007.

Program fact	What the record shows
Trials	Six randomized, double-blind, placebo-controlled studies, 2001–2006, sponsored by Metabolic Pharmaceuticals
Participants	893 otherwise-healthy, clinically obese adults
Routes and doses studied	Intravenous 25–400 µg/kg; oral 0.25–54 mg daily
Longest trial	24 weeks — no systematic human data exist beyond six months
Most-cited positive result	12 weeks at 1 mg oral daily: reported mean loss of 2.6 kg vs 0.8 kg on placebo (~1.8 kg placebo-adjusted); a 23-week study reported 2.8 kg vs 0.8 kg
Largest late-stage trial	536 obese adults, 24 weeks: failed to reach statistical significance for weight loss vs placebo
Dose–response	None consistent — higher doses performed no better than lower ones
Outcome	Development terminated 2007; no New Drug Application ever submitted

A few details deserve emphasis. The most-cited favorable figure — a mean 2.6 kg loss over 12 weeks at 1 mg oral daily, versus 0.8 kg on placebo — comes from secondary summaries of the program; the peer-reviewed literature documents the program's safety in detail while the efficacy results survive mainly in those secondhand accounts. Even taken at face value, the difference is about 1.8 kg (roughly 4 pounds) over three months. The decisive fact is the pivotal failure: in the 536-subject, 24-week study, the difference from placebo fell within statistical error margins. Higher doses did no better than lower ones — the program's reported pattern was a ceiling, not a curve. For scale, structured lifestyle interventions typically produce 5–10% body-weight loss.

That is why development stopped, and why the field moved on to compounds that cleared the bar the AOD-9604 program set out to clear. Tirzepatide, for example, completed its pivotal trials and earned full drug approval in 2022 for type 2 diabetes and in 2023 for chronic weight management; note that the tirzepatide available through compounding pharmacies is a compounded formulation — different from an FDA-approved product, and not itself FDA-approved. Promise does not currently offer AOD-9604; tirzepatide is among the metabolic treatments a Promise provider can discuss.

The safety record

Safety is the genuinely strong part of the AOD-9604 file — within its limits. Across the six trials, tolerability was described as indistinguishable from placebo: no drug-related withdrawals and no serious adverse events attributed to the compound. But the record covers oral and intravenous dosing in otherwise-healthy obese adults for at most 24 weeks, and nothing else.

The published safety review by Stier and colleagues (2013) lists the adverse events observed: headache, gastrointestinal symptoms, and upper respiratory infections — with a distribution similar to placebo. No participant developed anti-AOD-9604 antibodies in any assay, an important negative for a peptide drug. IGF-1 did not change, oral glucose tolerance tests showed no negative metabolic effect, and the joint discomfort and fluid retention typical of full growth hormone were not reported in the trials — though absence of reports over 24 weeks is weaker evidence than active long-term surveillance, which never happened.

The non-clinical toxicology is also reassuring on paper. A 2014 review by Moré and Kenley reports no genotoxicity across Ames, chromosome-aberration, and micronucleus testing, and chronic oral safety in rats and cynomolgus monkeys, with no-observed-adverse-effect levels at or above 100 mg/kg/day in rats and 50 mg/kg/day in monkeys.

Now the limits. There are no systematic human data beyond 24 weeks — a gap FDA itself has cited. More important for anyone reading peptide forums: the trials used oral and intravenous routes only. FDA's December 2024 review noted the absence of published human exposure data for the subcutaneous and topical routes — which are precisely the forms sold online. And product obtained outside regulated channels carries its own risks, unrelated to the molecule: no GMP manufacturing, unverifiable purity, potency, and sterility, no post-market surveillance, no authoritative dosing, and no adverse-event recourse. FDA's 2024 reviewers specifically flagged immunogenicity risk from peptide impurities and aggregates — a clean antibody record in pharmaceutical-grade trials says nothing about a gray-market vial.

The regulatory record, date by date

AOD-9604 has never been approved as a drug by any regulator, anywhere — not because an application was rejected, but because no application was ever filed. Its only regulatory credential is a self-affirmed GRAS determination, which is not an FDA review and covers only oral food use. The dates matter, so here they are.

Date	Event
1990s	Developed at Monash University (Frank Ng's group); drug development by Metabolic Pharmaceuticals, Melbourne
2001–2006	Six randomized, placebo-controlled trials in 893 obese adults
2007	Largest late-stage trial (536 subjects, 24 weeks) misses its weight-loss endpoints; development terminated; no NDA submitted
June 2012	Conditional self-affirmed GRAS — not an FDA action — announced for food-ingredient use, conditional on publishing the safety data
2013–2014	Safety data published (Stier 2013; Moré & Kenley 2014), completing self-affirmed GRAS — no FDA review — for oral use at about 1 mg/day
Sept 20, 2024	FDA removes AOD-9604 from Category 2 of the interim 503A bulks list after the original nomination is withdrawn
Dec 4, 2024	FDA's Pharmacy Compounding Advisory Committee reviews the re-nominated free base and acetate forms; FDA's staff evaluation weighs against listing, and the committee votes against recommending 503A inclusion
Today	Final 503A rulemaking still pending; the advisory posture is negative

Drug status versus food status. Much of the confusion around AOD-9604 comes from mixing these two lanes, so it is worth laying them side by side.

	As a drug	As a food ingredient
Status	Not approved by FDA or any other regulator; no NDA ever submitted	Self-affirmed GRAS — no FDA review — for oral use at about 1 mg/day, completed 2014
Who evaluated it	No regulator completed a review; development stopped in 2007	A company-convened expert panel, not FDA — there is no FDA GRAS notice or "no questions" letter on record
What it permits	Nothing — it cannot be marketed as a drug	Use in foods, drinks, and dietary supplements at the stated intake; it authorizes no therapeutic claims
Injectable use	FDA noted there are no published human exposure data for subcutaneous or topical routes	Nothing — the determination is oral-only

Self-affirmed GRAS status is not an FDA finding: it means the company convened its own expert panel, which concluded the ingredient is safe for a stated food use. For AOD-9604, Metabolic Pharmaceuticals announced the conditional determination in June 2012 and completed it in 2014 by publishing the pre-existing safety data. Vendors who wave "GRAS" as an approval — rather than the narrow oral-food-safety determination it is — are misusing the term in both directions.

The compounding question. Before December 2024, compounded AOD-9604 circulated through weight-loss clinics and compounding pharmacies under physician supervision — a gray area, since 503A compounders may in some cases use bulk substances that are not individually approved. The December 4, 2024 advisory committee vote, informed by an FDA staff evaluation citing inadequate physicochemical characterization, immunogenicity risk from impurities and aggregates, limited long-term safety data, lack of demonstrated clinical effectiveness, and no published human data for the proposed routes, points the other way: pending final rulemaking, compounding pharmacies largely cannot use AOD-9604, and legitimate compounded access has become rare.

Outside the United States, the pattern repeats: AOD-9604 is not approved by the European Medicines Agency, by Australia's TGA — which has issued warnings about unlicensed peptide products, including AOD-9604 — or by Health Canada.

AOD-9604 and drug testing in sport

For competitive athletes, the answer is short: AOD-9604 is prohibited in sport at all times under WADA's category S2 (Peptide Hormones, Growth Factors, and Related Substances), and a validated urine test can detect it at very low concentrations. Athletes face sanctions regardless of why they took it.

The analytical chemistry is well developed. A 2015 detection study validated a solid-phase-extraction urine method with a limit of detection of 50 pg/mL, precision better than 20%, and 62% recovery — and identified six potential metabolites in serum and urine incubations. One serum metabolite, the fragment CRSVEGSCG, proved significantly more stable than the parent peptide, which extends the practical detection window. The same paper notes the peptide had been identified in confiscated vials in the USA. Separately, 2013 work by the Cologne anti-doping group showed AOD-9604 does not interfere with WADA's hGH isoform immunoassay — it produces no false growth-hormone positives and is fully distinguishable from endogenous and injected hGH, so it is detected on its own terms.

Why AOD-9604 is still marketed

A drug candidate that failed its pivotal trial in 2007 still sells in 2026 for four understandable reasons: the growth-hormone halo, a genuinely plausible mechanism, a safety record that gets misread as an efficacy record, and anecdotes that have ordinary explanations.

The hGH association does heavy lifting — "a fragment of growth hormone" sounds potent, and the preclinical science is real. The clean tolerability data get quoted as if "safe" implied "effective," which the 536-subject trial answered directly. And the online success stories tend to come from people who started AOD-9604 alongside caloric restriction, new training programs, or other compounds — stacking, lifestyle co-changes, placebo response, and reporting bias can each account for the result. Randomized, placebo-controlled trials exist precisely to separate those factors, and when they did, the effect was small to absent.

For patients whose underlying interest is metabolic and cellular-energy support rather than this particular molecule, there are peptides with active intake pathways that a licensed provider can walk through — MOTS-c, a mitochondrial-derived peptide in Promise's catalog, is one place that conversation often goes.

Research beyond fat loss

AOD-9604 has a modest second life in preclinical research on cartilage and, more distantly, oncology — none of it in humans. Two lines of work exist, and both sit at the animal or cell-culture stage.

The more developed line is osteoarthritis. A 2015 study induced knee osteoarthritis in 32 mature New Zealand white rabbits (2 mg of type II collagenase, twice per knee), then gave weekly ultrasound-guided intra-articular injections during weeks 4–7: 0.6 mL saline, 6 mg hyaluronic acid, 0.25 mg AOD-9604, or the AOD-9604-plus-hyaluronic-acid combination. At 8 weeks, the combination group showed significantly lower gross and histopathological cartilage-degeneration scores than either treatment alone, and a significantly shorter period of lameness. A 2024 review in Cartilage lists AOD-9604 among peptides under investigation for chondrogenic induction and cartilage repair.

The oncology work is strictly in vitro: a 2022 study co-loaded hGH fragment 176-191 with doxorubicin in chitosan nanoparticles and found the dual-loaded particles more anti-proliferative against MCF-7 breast-cancer cells than doxorubicin-loaded particles alone, alongside favorable particle characteristics and in-silico docking results.

Neither application has advanced to human trials. These are reasons researchers remain curious, not reasons patients should seek the compound.

Where AOD-9604 stands today

AOD-9604 in 2026 is a discontinued drug candidate with an unusually complete paper trail: a genuinely clean short-term safety record, a failed efficacy program, no drug approval anywhere, a food-ingredient GRAS self-affirmation — not a drug review — covering about 1 mg per day orally, a December 2024 advisory-committee vote against compounding access, and a place on WADA's prohibited list. Any path back to drug status would require a new clinical program, and none is registered.

None of this makes the interest behind the search wrong. Wanting effective, medically supervised help with weight and metabolic health is exactly the right instinct — it just points toward compounds with living evidence and legitimate prescribing pathways rather than this one. Promise's catalog focuses on compounded metabolic and peptide therapies that a clinician can evaluate you for. At Promise, a licensed provider reviews every request; not everyone qualifies, and the provider may decline to prescribe.

References

Wu Z, Ng FM. Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. Biochem Mol Biol Int. 1993;30(1):187-96. PubMed
Natera SH, Jiang WJ, Ng FM. Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. Biochem Mol Biol Int. 1994;33(5):1011-21. PubMed
Heffernan MA, Thorburn AW, Fam B, et al. Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord. 2001;25(10):1442-9. PubMed
Heffernan M, Summers RJ, Thorburn A, et al. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology. 2001;142(12):5182-9. PubMed
Stier H, Vos E, Kenley D. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. J Endocrinol Metab. 2013;3(1-2):7-15. Publisher
Moré MI, Kenley D. Safety and Metabolism of AOD9604, a Novel Nutraceutical Ingredient for Improved Metabolic Health. J Endocrinol Metab. 2014;4(3):64-77. Publisher
Orlovius AK, Thomas A, Schänzer W, Thevis M. AOD-9604 does not influence the WADA hGH isoform immunoassay. Drug Test Anal. 2013;5(11-12):850-2. PubMed
Cox HD, Smeal SJ, Hughes CM, Cox JE, Eichner D. Detection and in vitro metabolism of AOD9604. Drug Test Anal. 2015;7(1):31-8. PubMed
Kwon DR, Park GY. Effect of intra-articular injection of AOD9604 with or without hyaluronic acid in rabbit osteoarthritis model. Ann Clin Lab Sci. 2015;45(4):426-32. PubMed
Habibullah MM, Mohan S, Syed NK, et al. Human Growth Hormone Fragment 176-191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells. Drug Des Devel Ther. 2022;16:1963-1974. PubMed
Liao HJ, Chen HT, Chang CH. Peptides for Targeting Chondrogenic Induction and Cartilage Regeneration in Osteoarthritis. Cartilage. 2024. PubMed
FDA Pharmacy Compounding Advisory Committee, meeting of December 4, 2024 — review of AOD-9604 (free base and acetate) for the 503A Bulk Drug Substances List. FDA meeting materials

This article is for education only and is not medical advice. Talk with a licensed healthcare provider about your own situation before starting or stopping any treatment.

Common questions

What is AOD-9604?

AOD-9604 is a synthetic peptide fragment of human growth hormone — amino acids 177–191 of the hormone's C-terminal region plus an added tyrosine, 16 amino acids in total. It was designed in the 1990s in Australia to reproduce hGH's fat-metabolism effects without its growth, IGF-1, or blood-sugar effects. It is the same molecule vendors sell as "modified hGH fragment 176-191."

Does AOD-9604 work for weight loss?

The trial record says: very little, if at all. Across six placebo-controlled trials in 893 obese adults, the most favorable reported result was a mean 2.6 kg loss over 12 weeks at 1 mg orally per day versus 0.8 kg on placebo — about 1.8 kg attributable to the compound — and the largest trial, 536 subjects over 24 weeks, found no statistically significant difference from placebo. Development ended in 2007 on that result. For comparison, structured lifestyle programs typically produce 5–10% body-weight loss.

What side effects did AOD-9604 trials report?

Across 893 trial participants, tolerability was indistinguishable from placebo. The reported adverse events — headache, gastrointestinal symptoms, upper respiratory infections — occurred at rates similar to placebo, no serious adverse events were attributed to the drug, and no participant developed antibodies against it. The caveats: the data cover oral and intravenous dosing only, for at most 24 weeks, in otherwise-healthy obese adults. There are no long-term safety data, no human data for injected subcutaneous use, and no safety data in pregnancy, breastfeeding, or children.

Is AOD-9604 FDA-approved?

No. AOD-9604 has never been approved as a drug by FDA — no New Drug Application was ever submitted, so no approval review ever took place — and on December 4, 2024, FDA's Pharmacy Compounding Advisory Committee voted against recommending it for the 503A compounding list. It does hold self-affirmed GRAS status (not an FDA review) as a food ingredient for oral use at about 1 mg per day — a food-safety determination, and not a drug approval of any kind.

Is AOD-9604 approved anywhere outside the U.S.?

No regulator has approved it. AOD-9604 is not approved by the European Medicines Agency, not approved by Australia's TGA — which has warned consumers about unlicensed peptide products including AOD-9604 — and not approved by Health Canada. Its development sponsor was Australian, and even there no marketing application succeeded.

Why was development discontinued if the safety data were good?

Because safety and efficacy are separate questions, and an obesity drug has to answer both. AOD-9604 was well tolerated, but its largest late-stage trial — 536 obese adults over 24 weeks — could not show statistically significant weight loss versus placebo, and the program found no consistent dose–response: higher doses did no better than lower ones. Metabolic Pharmaceuticals terminated development in 2007. A clean safety profile cannot rescue a compound that does not beat placebo.

Why is there no published AOD-9604 dosage chart?

Because no clinically validated dose exists. The trials used intravenous doses of 25–400 µg/kg and oral doses of 0.25–54 mg daily, found no consistent dose–response, and produced no approved product — so there is no drug label and no dosing authority. The microgram-range subcutaneous protocols circulating online have no clinical-trial basis at all: FDA's December 2024 review noted there are no published human exposure data for subcutaneous or topical routes. Any dosing chart you find is vendor lore, not evidence.

Can a doctor prescribe AOD-9604?

As a practical matter, rarely — and less each year. With no approved product, the only pharmacy route was compounded AOD-9604 made from bulk substance, and after the December 2024 advisory committee vote against 503A listing (final rulemaking pending), compounding pharmacies largely cannot use it. The earlier gray-market era fed a specific confusion — "my doctor prescribed it, so it must be vetted" — but a prescription does not change a substance's approval status. Prescribing decisions for any treatment sit between each patient and a licensed provider.

Is it legal to buy AOD-9604?

Possession for personal use is not explicitly illegal in most jurisdictions, but selling it for human use without approval violates federal law — the research-only disclaimer on vendor sites is a workaround that protects neither seller nor buyer effectively. Personal importation risks customs seizure, since FDA can seize shipments of unapproved drugs. Beyond legality, gray-market product is made outside GMP oversight, so purity, potency, and sterility are unverifiable.

Could a competitive athlete use AOD-9604?

Not without consequences. WADA prohibits AOD-9604 under category S2 (Peptide Hormones, Growth Factors, and Related Substances), and sanctions apply regardless of the reason for use. A validated urine test detects it down to 50 pg/mL, and a stable metabolite (CRSVEGSCG) extends the detection window beyond the parent peptide. It does not hide inside growth-hormone testing either — it is fully distinguishable from hGH on the isoform assay and is screened for in its own right.

Does AOD-9604 affect blood sugar or IGF-1?

Not in the human trials. Serum IGF-1 did not change, oral glucose tolerance tests showed no negative effect on carbohydrate metabolism, and no insulin-resistance signal emerged — a deliberate design goal, since full growth hormone does disturb glucose handling. In mouse studies, the fragment likewise avoided the hyperglycemia and reduced insulin secretion seen with full hGH. The limits apply here too: these findings cover at most 24 weeks of oral or intravenous use.

Why do some people report results with AOD-9604?

Usually because something else changed at the same time. Online reports typically involve stacking with other compounds, new diet or exercise habits, placebo response, or reporting bias — people who lose weight post about it, people who don't go quiet. Randomized, placebo-controlled trials are designed to strip those factors out, and when 893 participants were studied under those conditions, the placebo-adjusted effect was small to absent.