AICAR (Acadesine) Research Overview: Trials, Status, Doping

AICAR is not a peptide. It is a small nucleoside, 5-aminoimidazole-4-carboxamide ribonucleoside, that cells convert into a molecule resembling AMP, the signal that switches on the energy sensor AMPK [1][3]. Under the drug name acadesine it was tested in thousands of heart-surgery patients and in small leukemia trials. It is not an approved medicine in the sources we checked, and it is on the WADA Prohibited List [14][16].

Key points

• AICAR is a nucleoside prodrug, not a chain of amino acids. Inside cells it becomes ZMP, which mimics AMP and activates AMPK in the lab [1][5].
• A 2008 Cell paper reported that 4 weeks of AICAR raised running endurance by 44% in sedentary mice [2]. No human trial has tested that result in healthy people (we found none in ClinicalTrials.gov [18]).
• The human record is clinical, not athletic: a 3,080-patient heart-surgery trial of acadesine found no benefit and stopped for futility, and small leukemia trials ended with renal toxicity concerns [7][10][12].
• We found no medicine approval for AICAR or acadesine in the US drug database; the EU lists an orphan designation for leukemia, which is not an approval [13][14].
• AICAR is named as an example in the WADA 2026 list’s S4 category, and USADA has sanctioned an athlete for it [16][17].

What is AICAR and how was it found?

A registry title describes AICAR as a precursor of purine synthesis [18]. In 1995 Corton and colleagues reported that rat liver cells take it up and convert it to ZMP, which “mimics both activating effects of AMP” on AMPK, without changing cellular ATP, ADP or AMP [1]. That made it a convenient lab tool, and early AMPK biology leaned on it heavily [3]. We did not trace who first synthesised the compound or first named it acadesine.

Does AICAR activate AMPK, and what does that mean?

In cells, yes. But a 2021 systematic review of AICAR studies found a growing number of effects, previously attributed to AMPK, that turned out to be AMPK-independent, and urged caution when reading AICAR-based work [3]. In a human study of 22 adults, an AICAR infusion increased glucose uptake in thigh muscle while AMPK activity was unchanged at the 3-hour biopsy; another kinase, ERK1/2, rose instead [4]. So “AICAR activates AMPK” is a cell-culture statement; in people the mechanism is less settled.

Does AICAR work like exercise?

The “exercise mimetic” label comes from Narkar and colleagues, Cell, July 2008. In sedentary adult mice, 4 weeks of AICAR induced metabolic genes and increased treadmill endurance by 44% [2]. The same paper showed a PPAR-delta agonist plus training worked synergistically [2]. We read only the abstract, so group sizes and funding are unverified.

Later work is mixed in scope rather than clearly contradictory. A 2025 study of 23-month-old mice found that 31 days of AICAR treatment prevented a 24.5% decline in treadmill capacity seen in saline-treated old mice, and was associated with about 8% heavier quadriceps and 26.4% higher EDL muscle force [5]. All of this is rodent treadmill work. A 2025 review in Trends in Endocrinology & Metabolism concluded that exercise pills “cannot mimic the exercise milieu” [19]. Endurance in a mouse is not training adaptation in a person.

What do the human studies show?

Heart surgery (acadesine). A 1997 JAMA pooled analysis of five placebo-controlled trials (4,043 coronary bypass patients) reported a 27% lower rate of perioperative heart attack (odds ratio 0.69) and no significant effect on stroke [6]. The later RED-CABG trial, a double-blind trial in intermediate- to high-risk patients at 300 sites in 7 countries, randomised 3,080 people and stopped early after a futility analysis. The primary outcome (death, nonfatal stroke or need for mechanical heart support at 28 days) occurred in 5.1% on acadesine and 5.0% on placebo, odds ratio 1.01 [7]. The registry lists Merck Sharp & Dohme as sponsor [8]; the ACC summary names Schering-Plough [9].

Leukemia. A Phase 1/2 open-label trial (NCT00559624; 8 sites in Belgium, France and Spain; 2007-2010) gave acadesine to 24 patients with relapsed or refractory chronic lymphocytic leukemia [10][11]. Single doses reached a maximum tolerated level; at the highest, 2 of 3 patients had dose-limiting tumor lysis syndrome and renal impairment. Authors reported anti-leukemic activity (more than 20% drop in B cells or lymph node size) in 16 of 24, called it provisional, and no formal response criteria were used [10]. The registry planned 40 patients, so enrolment fell short, and no results are posted [11].

A French Phase 1/2 trial in myelodysplastic syndromes and acute myeloid leukemia (NCT01813838) enrolled 5 people and was terminated with the stated reason “Renal toxicity” [12]. We found no later registered acadesine trials in that search [18].

Other. A Phase II pilot of AICAR for Lesch-Nyhan disease is registered as completed; we saw only the title and status [18]. We found no trial of AICAR in healthy people.

Regulatory status

• United States, as of 2026-11-09. Searches of the openFDA Drugs@FDA dataset for acadesine, AICAR and “AICA riboside” returned no records, whereas a control search (aspirin) did [14]. That dataset covers approved applications only. We did not search the FDA orphan drug database.
• European Union. Acadesine holds orphan designation EU/3/05/280 for B-cell chronic lymphocytic leukemia, decided 2005-05-27 for Advancell; the Commission register shows status “ACTIVE” [13]. EMA’s own page returned an error, so we did not read it. We did not search the register of authorised medicines.
• United Kingdom (MHRA) and Germany (BfArM): not checked.
• Sport. The WADA 2026 Prohibited List (in force 2026-01-01) names AICAR in S4, as an example of an AMPK activator, next to MOTS-c [16]. Our copy is a Cologne anti-doping laboratory’s reproduction, not WADA’s PDF, which we could not open. For MOTS-c see our overview. In 2017 USADA announced a four-year sanction for a Moroccan track athlete after non-analytical evidence showed possession and use of AICAR, which he admitted despite a “not for human consumption” label [17]. We found no other primary-source case.

What “research use only” means

The label says a product is sold for laboratory work, not as a medicine for people. It does not make the product legal to market for human use. In an August 2026 warning letter to a peptide seller (not naming AICAR), FDA wrote that evidence from the seller’s website “establishes that your products are intended to be drugs for human use” despite such labels [15]. We did not review any seller’s wording, so we cannot say how AICAR vendors describe it.

Risks and unknowns

Documented effects come from patients under surgery or cancer care, not from healthy people. In the CLL trial, hyperuricemia of grade 2 or higher was common and controlled with allopurinol (one grade 4 case at the lowest dose); four patients had reversible renal impairment; three had transient infusion-related hypotension; mild anemia and low platelets occurred. We found no mention of lactic acidosis in that paper [10]. In RED-CABG, serious adverse events were about 23% in both arms (327 of 1,442 versus 329 of 1,457) [8]. The myelodysplasia trial stopped for renal toxicity [12].

Not studied: use in healthy adults, long-term exposure, interactions, pregnancy, and the purity or identity of products sold as research chemicals. The clinical safety data belong to intravenous pharmaceutical acadesine, which may not resemble a chemical from an unregulated source. AMPK-independent effects mean mechanism-based reasoning is unreliable [3].

Prices for this research chemical are on the AICAR compound page.

Frequently asked questions

Is AICAR a peptide? No. It is a nucleoside, a sugar attached to a modified base, and a precursor of the AMP-like molecule ZMP [1]. Shops often list it with peptides, which is a retail grouping.

Is AICAR legal or approved? We found no medicine approval in the US Drugs@FDA data, and the EU entry is an orphan designation for leukemia, not an approval [13][14]. UK and German status were not checked.

Is AICAR banned in sport? It is named as an AMPK-activator example in S4 of the WADA 2026 list as reproduced by a university laboratory, and USADA has sanctioned an athlete for it [16][17].

What do the human studies show? Acadesine did not improve outcomes in the 3,080-patient RED-CABG trial. Leukemia trials were small and reported renal and uric acid problems [7][10][12].

Is AICAR safe? Safety is unknown outside monitored clinical settings. Trial data show renal and uric acid effects, and nothing covers healthy users [10][12].

Sources

1. Corton JM, Gillespie JG, Hawley SA, Hardie DG, European Journal of Biochemistry, “5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells?” (1995-04-01). PMID 7744080, via Europe PMC (abstract only).
2. Narkar VA et al., Cell, “AMPK and PPARdelta agonists are exercise mimetics” (2008-07-31). PMID 18674809, via Europe PMC (abstract only).
3. Višnjić D et al., Cells, “AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review” (2021-05-04). PMID 34064363, via Europe PMC (abstract only).
4. Babraj JA et al., American Journal of Physiology Endocrinology and Metabolism, “Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status” (2009-02-03). PMID 19190259, via Europe PMC (abstract only).
5. Wilcox SH et al., FASEB BioAdvances, “Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression” (2025-01-29). PMID 40060947, via Europe PMC (abstract only).
6. Mangano DT, JAMA, “Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials” (1997). PMID 9002496, via Europe PMC (abstract only).
7. Newman MF et al., JAMA, “Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial” (2012). PMID 22782417, via Europe PMC (abstract only).
8. ClinicalTrials.gov, NCT00872001, acadesine in coronary artery bypass graft surgery (Merck Sharp & Dohme; terminated; results posted December 2012), read 2026-11-09. https://clinicaltrials.gov/study/NCT00872001
9. American College of Cardiology, “Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG - RED-CABG” (2012-07-18). https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2012/07/18/16/20/RED-CABG
10. Van Den Neste E et al., Cancer Chemotherapy and Pharmacology, “Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicenter phase I/II study” (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3579463/ (open-access full text; funding and conflict statements were not seen)
11. ClinicalTrials.gov, NCT00559624, acadesine in B-CLL (Advancell; completed December 2010; results not posted), read 2026-11-09. https://clinicaltrials.gov/study/NCT00559624
12. ClinicalTrials.gov, NCT01813838, “GFM-Acadesine: A Phase I-II Trial of Acadesine” (Groupe Francophone des Myelodysplasies; terminated, “Renal toxicity”; 5 enrolled), read 2026-11-09. https://clinicaltrials.gov/study/NCT01813838
13. European Commission, Union Register of medicinal products, orphan designation EU/3/05/280, acadesine (decision 2005-05-27; status ACTIVE), read 2026-11-09. https://ec.europa.eu/health/documents/community-register/html/o280.htm
14. FDA openFDA, Drugs@FDA API searches for ACADESINE, AICAR and AICA RIBOSIDE (no matches; aspirin control returned a record), run 2026-11-09. https://api.fda.gov/drug/drugsfda.json
15. FDA, Warning Letter to Peak Performance Peptides, ref. 735127 (2026-08-24). https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/peak-performance-peptides-735127-08242026
16. Deutsche Sporthochschule Köln, Department of Biochemistry, “Hormones and Metabolic Modulators” (S4), reproducing the WADA Prohibited List edition of 2026-01-01. https://www.dshs-koeln.de/en/universitaet/organisation/institute-einrichtungen/department-of-biochemistry/doping-substances/prohibited-classes-of-substances-and-methods/s4-hormones-and-metabolic-modulators (WADA’s own list not opened)
17. USADA, “Track & Field Athlete Abdelmounaim Harroufi Receives Sanction for Anti-Doping Rule Violations” (2017-12-08). https://www.usada.org/sanction/abdelmounaim-harroufi-receives-doping-sanction/
18. ClinicalTrials.gov searches for “acadesine” (interventions) and “AICAR” (all fields), run 2026-11-09; NCT00004314 (Lesch-Nyhan, completed) seen as title and status only. https://clinicaltrials.gov/
19. Plaza-Florido A et al., Trends in Endocrinology and Metabolism, “Exercise pills for cardiometabolic health cannot mimic the exercise milieu” (2025-08-09). PMID 40784868, via Europe PMC (abstract only).

This article is information, not medical advice.