IngredientsDimethylamylamine (DMAA) is an aliphatic amine with sympathomimetic properties that has been referred to by numerous names, including methylhexaneamine, 2-amino-4-methylhexane, forthane, and geranamine, since its inception in 1944. 1,3-Dimethylamylamine is listed under the International Union of Pure and Applied Chemistry (IUPAC) name 4-methylhexan-2-amine (Chemical Abstracts Service number: 105-41-9). It is also known as methylhexanamine, methylhexaneamine, 2-amino-4-methylhexane, 4-methyl-2-hexylamine, and 1,3-dimethylpentylamine, and under the trade names Geranamine and Floradrene.
DMAA's chemical formula is C₇H₁₅NO. Its structure includes a seven-carbon backbone with a methyl group attached to the third carbon. DMAA has different chemical isomers, which are molecules with the same molecular formula but arranged differently. 1,3-Dimethylamylamine is not a single compound but rather a mixture of four stereoisomers.
Methylhexanamine is closely structurally related to other alkylamines, including 1,3-dimethylbutylamine (1,3-DMBA), 1,4-dimethylamylamine (1,4-DMAA), heptaminol, iproheptine, isometheptene, octodrine, and tuaminoheptane. Methylhexanamine and these related alkylamines are similar in chemical structure to phenethylamines and amphetamines, but lack a closed ring.
1,3-Dimethylamylamine is an aliphatic amine with stimulant properties that are reportedly found naturally only in geranium plants (Pelargonium graveolens). The presence of 1,3-DMAA in geranium plants was first reported in a paper published in 1996, but some have questioned the identification of 1,3-DMAA in that study. Since then, a number of additional studies have been published, largely reporting the absence of 1,3-DMAA in geranium plants and commercial geranium oils. However, in two recent studies, 1,3-DMAA was detected in geranium plant tissues and a geranium oil sample using a simplified extraction approach on tissues and oil sourced from China.
While some analytical studies have reported finding DMAA in geranium plants, others have not, and differences in sample sources, extraction procedures, and methods of analysis may account for the conflicting results. DMAA was not found in any of the leaves or stems or in the commercial geranium oil included in one study's analysis.
In one study, the enantiomeric and diastereomeric ratios of two different known synthetic DMAA compounds, as well as the total concentrations of DMAA and its stereoisomeric ratios in 13 different supplements, were determined by gas chromatography. The stereoisomeric ratios of DMAA in the synthetic standards and in all the commercial supplements were indistinguishable. The amount of DMAA that is found in dietary supplements was shown to be too high to be solely derived from natural geranium extracts. The FDA has stated that DMAA is often touted as a "natural" stimulant; however, the FDA is not aware of any reliable science indicating that DMAA exists naturally in plants.
DMAA reentered the market in 2006 as a component of nutritional supplements with stimulant properties and was used as an additive in nutritional and sports supplements for many years. Sports supplement companies initially claimed that DMAA was derived naturally from rose geranium oil and used the names rose geranium, geranium oil, and geranium stems on their product labels. DMAA has been marketed as an exercise stimulant and appetite suppressant, as have its structural analogs 1,4-DMAA and 1,3-dimethylbutylamine, being included in over 200 products.
DMAA, also known as methylhexanamine, 1,3-dimethylamylamine, and geranium extract, was the main active ingredient in products such as Jack3d, OxyElite Pro, Hemo Rage Black, Creafuse, and many other dietary supplements. DMAA has appeared commercially as a powder, capsule, and liquid preparation, typically as a component in multi-ingredient pre-workout and weight-loss supplement blends.
Methylhexanamine (trade names Forthane and Geranamine) is an indirect sympathomimetic drug invented and developed by Eli Lilly and Company and marketed as an inhaled nasal decongestant from 1948 until it was voluntarily withdrawn from the market in the 1980s. American pharmaceutical giant Eli Lilly filed a patent on DMAA in 1944 and trademarked the compound as Forthane in 1971.
Initially developed in 1944 by Eli Lilly as a nasal decongestant, the vasoconstrictive and sympathomimetic efficacy of DMAA was well characterized. Original reports indicated that DMAA was a less potent and longer-lasting vasoconstrictor compared to epinephrine with systemic toxicity greater than ephedrine, but less than amphetamine. Similarly, DMAA was shown to increase blood pressure in dogs in early pharmacological studies.
Although DMAA at one time was approved as a drug for nasal decongestion, it is no longer approved for this use and no medical use of DMAA is recognized today.
DMAA was patented by Eli Lilly and Co. in 1944 as a nasal decongestant called Forthane, but the drug was quietly withdrawn in the 1970s, a time when medications were beginning to face increased regulation. The drug spent decades in obscurity before beginning to appear in sports dietary supplements, often as a replacement for ephedra.
Chemist Patrick Arnold, who developed the designer steroids at the heart of the professional sports doping scandal that snared several prominent athletes, trademarked methylhexaneamine or DMAA as Geranamine. DMAA was not in supplements prior to the Dietary Supplement and Health Education Act of 1994 (DSHEA); hence, DMAA would be classified as a New Dietary Ingredient (NDI) by the Food and Drug Administration (FDA).
DMAA (1,3-dimethylamylamine), also called methylhexaneamine, is an alkylamine structurally related to amphetamine. DMAA is a sympathomimetic and potent pressor agent. Whereas the sympathomimetic effects of DMAA have been characterized, its exact pharmacological mechanism has not been definitively established.
Like other sympathomimetics, acute use of DMAA appears to promote vasoconstriction, which can lead to a dose-dependent elevation in blood pressure. It was first studied in the 1940s and 1950s, when researchers documented its ability to mimic adrenaline throughout the body. It constricts blood vessels, raises blood pressure, speeds up heart rate, and increases blood sugar.
There is scant research describing the mechanism of action of DMAA, making it difficult to gauge risks or therapeutic potential. An important molecular target of structurally related phenethylamines, such as amphetamine, for regulating mood, cognition, movement, and the development of substance use disorder is the dopamine transporter, which limits the range and magnitude of dopamine signaling via reuptake from the extracellular space.
Docking analysis and molecular dynamics simulations revealed that DMAA binds to the S1 substrate binding site and induces a conformational change from outward-facing open to outward-facing closed states, similar to known substrates. Further supporting substrate-like effects of DMAA, the drug stimulated dopamine transporter endocytosis in a heterologous expression system via cocaine- and protein kinase A–sensitive mechanisms, mirroring findings with amphetamine. Together, these data indicate that DMAA elicits neurologic effects by binding to and regulating function of the dopamine transporter.
DMAA inhibits dopamine uptake in a competitive manner. Pharmacologic distinctions from amphetamine reveal structural determinants for regulating transporter conformation and add mechanistic insight for the regulation of dopamine transporter endocytosis. These findings are based on laboratory and in vitro studies; human clinical data directly demonstrating these neurochemical mechanisms are not yet available.
Dose-response studies of DMAA were performed with Swiss-Webster mice in locomotor and conditioned place-preference assays. The discriminative stimulus effects of DMAA were investigated in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from saline. DMAA produced dose-dependent locomotor depression and fully substituted for cocaine and partially substituted for methamphetamine. In the conditioned place-preference assay, DMAA produced an inverted-U-shaped dose-response curve, with intermediate doses producing significant place preference. These findings are preclinical (animal-based) and their applicability to human abuse potential requires further study.
Further study will be necessary to confirm drug seeking behavior (e.g., self-administration) and mechanism of action. DMAA produces behavioral effects similar to adrenergic compounds, but it will be necessary to directly test the mechanism of action of the discriminative stimulus and rewarding effects of DMAA.
Lag time, the delay in appearance of DMAA in the circulation following extravascular administration, varied among participants but averaged approximately 8 minutes. The peak DMAA concentration for all subjects was observed within 3–5 hours following ingestion and was very similar across subjects, with a mean of approximately 70 ng·mL⁻¹.
Analysis showed DMAA had an oral clearance of 20.02 ± 5 L·hr⁻¹, an oral volume of distribution of 236 ± 38 L, and a terminal half-life of 8.45 ± 1.9 hr. These findings indicate a consistent pattern of increase across subjects with regards to peak DMAA concentration, with peak values approximately 15–30 times lower than those reported in case studies linking DMAA intake with adverse events. A single 25 mg dose of DMAA does not meaningfully impact resting heart rate, blood pressure, or body temperature.
DMAA's original and only formally approved application was as an inhaled nasal decongestant, developed and marketed by Eli Lilly from 1948 until voluntary market withdrawal in the 1980s. Initially developed in 1944 by Eli Lilly as a nasal decongestant, the vasoconstrictive and sympathomimetic efficacy of DMAA was well characterized. Original reports indicated that DMAA was a less potent and longer-lasting vasoconstrictor compared to epinephrine with systemic toxicity greater than ephedrine, but less than amphetamine. No contemporary clinical trials have been conducted or published evaluating DMAA for nasal congestion, and this use is no longer approved or recognized.
Few human studies have been conducted using DMAA or DMAA-containing supplements. Scant data exist regarding its precise mechanism(s) of action in the context of exercise.
A study by Bloomer et al. (2011) published in The Physician and Sportsmedicine examined the effects of DMAA and caffeine, alone or in combination, on heart rate and blood pressure in healthy men and women. The use of supplements containing DMAA and caffeine was found to increase blood pressure in the short-term, with a peak at 60–90 minutes post-ingestion, with minimal effects on heart rate.
A 10-week intervention study (Whitehead et al., 2012, published in Nutrition and Metabolic Insights) examined the impact of a supplement containing 1,3-DMAA on blood pressure and bloodborne markers of health. 25 healthy men were randomly assigned to either a placebo (n=13) or a supplement containing 1,3-dimethylamylamine (n=12) for a period of 10 weeks. Prior work with this agent indicated a transient increase in blood pressure (systolic in particular) following oral ingestion of a single dosage, but no significant increase in resting blood pressure following chronic ingestion. Moreover, intervention studies involving both two and eight weeks of treatment with finished products containing 1,3-dimethylamylamine indicated minimal or no change in bloodborne markers of health.
The daily ingestion of DMAA-containing supplements for periods between 14 days and 12 weeks had no pathological consequences in the studied populations. It is important to note that virtually all of these controlled studies used finished products containing multiple active ingredients alongside DMAA, making it difficult to isolate DMAA's individual contribution to performance outcomes. The body of human evidence is very limited in scope, with small sample sizes and short durations.
The alkylamine stimulant 1,3-dimethylamylamine is used nonmedically as an appetite suppressant and exercise performance enhancer despite adverse cardiovascular effects that have limited its legal status. No high-quality, adequately powered randomized controlled trials have been published that specifically and rigorously evaluate DMAA as a monotherapy for weight loss in humans. Evidence in this domain is limited to small studies using multi-ingredient supplements, anecdotal reports, and animal studies. No systematic reviews or meta-analyses exist for DMAA's use as an appetite suppressant. Evidence in this area must be characterized as preliminary and insufficient.
The alkylamine stimulant 1,3-dimethylamylamine is structurally similar to amphetamine. Given its dopamine transporter interactions (demonstrated in preclinical studies), DMAA is hypothesized to exert stimulant effects on mood and energy. There is scant research describing the mechanism of action of DMAA, making it difficult to gauge risks or therapeutic potential. No adequately controlled human clinical trials assessing cognitive performance outcomes for DMAA have been identified in the peer-reviewed literature. Any claims regarding cognitive enhancement are not supported by clinical evidence.
DMAA has been marketed in capsule and powder forms, often as a component of multi-ingredient pre-workout and weight-loss supplements. The following dosages have been reported in published scientific literature:
It should be noted that these dosages are reported descriptively from published studies and do not represent recommended or approved therapeutic doses. No regulatory agency has established a safe or effective dose of DMAA for any indication.
DMAA (1,3-dimethylamylamine) is an amphetamine derivative that has been marketed in sports performance and weight loss products. This substance narrows blood vessels and can cause cardiovascular problems such as shortness of breath, arrhythmias, tightening in the chest, and heart attack, as well as seizures and other neurological and psychological conditions.
The cardiovascular system has been the primary area of documented concern. Dietary supplements containing 1,3-DMAA have been linked in case reports to cardiac arrest and hypoxic-ischemic injury, acute cardiac failure due to extreme physical exertion, cerebral hemorrhage, hypertension, NSTEMI, exertional heat stroke, atrial fibrillation with rapid ventricular response, and necrotizing myopathy. This does not mean that 1,3-DMAA was the cause of these situations, as case reports are not meant to establish causation but to allow for the development of a hypothesis, which can then be tested.
DMAA elicits neurologic effects by binding to and regulating function of the dopamine transporter. Reported neurological adverse events in case reports include cerebral hemorrhage and seizures. Cohen points out the similarities between DMAA and amphetamines and discusses DMAA as a possible cause of several adverse effects such as hemorrhagic stroke, seizures and stress-induced cardiomyopathy reported in case studies.
DMAA is also associated with severe liver injury. Researchers linked the use of OxyElite Pro, a supplement containing DMAA, to at least 36 cases of hepatotoxicity.
Case reports have described rhabdomyolysis (muscle breakdown) and kidney failure in association with DMAA-containing supplements, though multi-ingredient formulas make definitive attribution difficult.
Since 2006 methylhexanamine has been sold extensively under many names as a stimulant or energy-boosting dietary supplement; its safety has been questioned as a number of adverse events and at least five deaths have been associated with methylhexanamine-containing supplements.
Three cases of cerebral hemorrhage in adults after the use of DMAA were described in a case series published in the Annals of Emergency Medicine.
Case reports were presented for two soldiers who were taking commercially available dietary supplements containing multiple ingredients including the sympathomimetic 1,3-dimethylamylamine (DMAA); both collapsed and died. A subsequent U.S. military safety panel report concluded that "DMAA did not play a significant role in the deaths of these four Service members." A similar conclusion came from a survey which included 712 soldiers diagnosed with cardiac dysrhythmia, heat injury, seizure, rhabdomyolysis, cerebral hemorrhage, acute kidney failure, or acute/subacute necrosis of the liver. The analysis found that, compared to 1,077 randomly selected controls, these soldiers were no more likely to have used DMAA. These conflicting findings illustrate the ongoing evidentiary uncertainty around DMAA causality in specific adverse events.
Reports indicate that use of dietary supplements containing 1,3-DMAA was associated with multiple self-reported adverse events, including tachycardia, tremors, dizziness, and numbness/tingling sensations.
DMAA, especially in combination with other stimulant ingredients such as caffeine, can be a health risk to consumers. Documented health incidents linked to the compound include heart attack, cardiac arrest, stroke, and brain hemorrhage. These risks are compounded when DMAA is consumed with other common stimulants like caffeine.
The Department of Defense (DoD) operates six forensic urine drug-testing laboratories that screen close to 5 million urine samples for amphetamines yearly. The DoD laboratories have observed a significant decrease in the confirmation rates for amphetamines because of specimens screening positive by two separate immunoassays and confirming negative by gas chromatography-mass spectrometry (GC-MS). Additional information obtained from an immunoassay vendor suggested that the anorectic compound dimethylamylamine (DMAA) may be the cause of these false-positive screens. DMAA was found in 92.3% of the false-positive amphetamine samples that were then confirmed to be negative by GC-MS.
DMAA is not a dietary ingredient, and DMAA-containing products marketed as dietary supplements are illegal and their marketing violates the law. In 2012, the FDA issued warning letters to manufacturers and distributors calling for cessation of DMAA sales and use within dietary supplement formulations, partly because required safety data supporting DMAA's use was lacking.
A number of adverse cardiovascular events led to safety evaluation and, eventually, banning by the US Food and Drug Administration. Regulatory agencies in Australia, Canada, and New Zealand have also banned the sale of DMAA.
Methylhexaneamine (DMAA), an amphetamine derivative banned by the World Anti-Doping Agency (WADA) in 2009, has caused more positive tests than any other stimulant. DMAA is classified as a stimulant and is banned by various sports organizations due to its amphetamine-like nature; it is prohibited in-competition by WADA under the category of "Non-Specified Stimulants."
Reports of adverse events associated with 1,3-DMAA use are cause for safety concerns, and the available data are insufficient to support the safety of 1,3-DMAA for use in foods generally. The FDA does not have any information to demonstrate that consuming DMAA is safe.
Due to persistent regulatory challenges and FDA enforcement actions, DMAA is virtually absent from major retail chains, established supplement stores, and reputable online platforms. Mainstream businesses removed the ingredient to avoid legal repercussions and consumer safety issues. This disappearance from legitimate commerce has pushed the sale of DMAA into a less regulated space. The substance can still be found through niche online vendors and in the "gray market" of the supplement industry.
Health conditions that Dimethylamylamine may help support.
Dimethylamylamine (DMAA; 1,3-dimethylamylamine) is a potent synthetic sympathomimetic stimulant used in thermogenic supplements for its adrenergic thermogenic and fat-mobilizing effects. It significantly increases energy expenditure and metabolic rate via norepinephrine-releasing activity. Banned by the FDA for dietary supplements due to serious cardiovascular adverse events.
Body systems that Dimethylamylamine may help support.
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