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DMHA: Clarifying the Ambiguity of This Potent Stimulant
In 2013, a stimulant drink called Clearshot by E-Pharm was released and it was formulated by none other than infamous chemist Patrick Arnold. It contained an ambiguously named stimulant "2-aminoisoheptane" that no one had really heard of at this point.
Reviews for this product were very good, but for some reason it never really caught on to the masses.
Fast forward to 2016, when DMAA's legality was being investigated by the FDA and the courts. Companies began looking for a viable replacement. There was a slight buzz around a new stimulant that was very similar in structure to DMAA, but there was a lot of confusion about the actual name and structure of what was being called 2-aminoisoheptane or DMHA.
Let's break it down by parts:
Heptane means there are 7 total carbons in the molecule. The term iso means that there is a methyl group that branches out of the linear carbon chain. For isoheptane, that methyl group can be either on the 3rd, 4th, or 5th carbon in the chain of 6 carbons (6 carbons plus the 1 methyl group is 7 carbons for heptane). The only part we know for sure is that there is an amine group on carbon 2.
So, the most accurate name for the structure would be 2-amino-5-methylhexane or 5-methyl-2-hexanamine. But, that is not the molecule that is found in nature and what most companies are using. To add to the confusion even more, the actual molecule found in nature in Kigelia Africana fruit extract is 2-amino-6-methylheptane, or 2-aminoisooctane (because now there are 8 total carbons, not 7).
Somewhere along the way, DMHA was also coined for this compound, I believe by Bruce Kneller which stands for 1,5-dimethylhexanamine. This doesn't specifically tell you where the amine group is, but its catchy and marketable, especially as a DMAA replacement. This is usually the molecule found in your supplements.
There is also a 2-amino-5-methylheptane that is found in nature in the bark of the Juglans regia tree. However, due to cost, most companies use 2-amino-6-methylheptane in their products.
So, now that we are all talking about the same molecule, 2-amino-6-methylheptane or DMHA, what do we actually know about it? Well, it was investigated as a nasal decongestant (as was DMAA) in the 1950's. In fact, it was the active ingredient in the decongestant Eskays Oralator that contained 350mg of it!
There is not a lot of human data for DMHA, but there are some animal pharmacology papers. In a 1952 study in dogs, tested various octlyamines similar in structure to DMHA showed these compounds had a similar mechanism of action of amphetamine, but with less stimulation and cardiac activity.
As you can see when comparing structures of DMHA, DMAA and amphetamine, you'll notice that all the compounds have a polar amine group on carbon 2 and then have an extremely lipophilic (greasy) carbon chain/ring. This is known as amphiphilic (containing polar and nonpolar sections) which allow it to readily cross the blood-brain barrier.
DMHA also possesses a methyl group on the alpha carbon that stericly hinders monoamine oxidase, which should give it a similar half-life to DMAA or amphetamine (both half-lives are around 9-11hr). Also, based on its similar structure to DMAA, DMHA should act as a monoamine releasing agent (MRA) of catecholamines such as dopamine and norepinephrine.
An MRA is taken up by transcellular catecholamine channels and the primary location for action is the terminal nerve ends that extend from the sympathetic nervous system to organs like your heart, kidneys, and vasculature nerves. This is where MRAs cause a localized release of norepinephrine which subsequently increases heart rate and renal vasodilaion (via beta-1 adrenergic activity) and peripheral vasoconstriction (via alpha-1 adrenergic activity).
This explains the side effects normally felt when you take a very strong stimulant like DMAA or DMH. When DMHA binds to the trace amine associated receptor 1, it will temporarily prevent the reuptake of dopamine and norepinephrine into the presynaptic nerve.
By blocking their reuptake, catecholamines like dopamine and norepinephrine stay active longer in your body and produces the feelings of euphoria and wakefulness (from the dopamine and norepinephrine).
Sadly, as of 2017, there no real human data on DMHA exists which makes it hard to predict an accurate dose. One study in rats showed that the oral LD50 is 538mg/kg, which equates to 87mg/kg in humans.
Some websites recommend 1mg/kg as a "safe" starting dose, but this has not been substantiated. There's also no data to support if it can burn fat, elevate energy expenditure, raise body temperature, increase performance or have any exergonic benefits for athletes.
Reviews for this product were very good, but for some reason it never really caught on to the masses.
Fast forward to 2016, when DMAA's legality was being investigated by the FDA and the courts. Companies began looking for a viable replacement. There was a slight buzz around a new stimulant that was very similar in structure to DMAA, but there was a lot of confusion about the actual name and structure of what was being called 2-aminoisoheptane or DMHA.
DMHA - What's in a Name?
In chemistry, there is a very specific set of guidelines, the IUPAC System, for naming molecules so there is no ambiguity. The name 2-aminoisoheptane does not describe just one molecule, but multiple variations of that molecule.Let's break it down by parts:
Heptane means there are 7 total carbons in the molecule. The term iso means that there is a methyl group that branches out of the linear carbon chain. For isoheptane, that methyl group can be either on the 3rd, 4th, or 5th carbon in the chain of 6 carbons (6 carbons plus the 1 methyl group is 7 carbons for heptane). The only part we know for sure is that there is an amine group on carbon 2.
So, the most accurate name for the structure would be 2-amino-5-methylhexane or 5-methyl-2-hexanamine. But, that is not the molecule that is found in nature and what most companies are using. To add to the confusion even more, the actual molecule found in nature in Kigelia Africana fruit extract is 2-amino-6-methylheptane, or 2-aminoisooctane (because now there are 8 total carbons, not 7).
Somewhere along the way, DMHA was also coined for this compound, I believe by Bruce Kneller which stands for 1,5-dimethylhexanamine. This doesn't specifically tell you where the amine group is, but its catchy and marketable, especially as a DMAA replacement. This is usually the molecule found in your supplements.
There is also a 2-amino-5-methylheptane that is found in nature in the bark of the Juglans regia tree. However, due to cost, most companies use 2-amino-6-methylheptane in their products.
So, now that we are all talking about the same molecule, 2-amino-6-methylheptane or DMHA, what do we actually know about it? Well, it was investigated as a nasal decongestant (as was DMAA) in the 1950's. In fact, it was the active ingredient in the decongestant Eskays Oralator that contained 350mg of it!
There is not a lot of human data for DMHA, but there are some animal pharmacology papers. In a 1952 study in dogs, tested various octlyamines similar in structure to DMHA showed these compounds had a similar mechanism of action of amphetamine, but with less stimulation and cardiac activity.
As you can see when comparing structures of DMHA, DMAA and amphetamine, you'll notice that all the compounds have a polar amine group on carbon 2 and then have an extremely lipophilic (greasy) carbon chain/ring. This is known as amphiphilic (containing polar and nonpolar sections) which allow it to readily cross the blood-brain barrier.
DMHA also possesses a methyl group on the alpha carbon that stericly hinders monoamine oxidase, which should give it a similar half-life to DMAA or amphetamine (both half-lives are around 9-11hr). Also, based on its similar structure to DMAA, DMHA should act as a monoamine releasing agent (MRA) of catecholamines such as dopamine and norepinephrine.
An MRA is taken up by transcellular catecholamine channels and the primary location for action is the terminal nerve ends that extend from the sympathetic nervous system to organs like your heart, kidneys, and vasculature nerves. This is where MRAs cause a localized release of norepinephrine which subsequently increases heart rate and renal vasodilaion (via beta-1 adrenergic activity) and peripheral vasoconstriction (via alpha-1 adrenergic activity).
This explains the side effects normally felt when you take a very strong stimulant like DMAA or DMH. When DMHA binds to the trace amine associated receptor 1, it will temporarily prevent the reuptake of dopamine and norepinephrine into the presynaptic nerve.
By blocking their reuptake, catecholamines like dopamine and norepinephrine stay active longer in your body and produces the feelings of euphoria and wakefulness (from the dopamine and norepinephrine).
Sadly, as of 2017, there no real human data on DMHA exists which makes it hard to predict an accurate dose. One study in rats showed that the oral LD50 is 538mg/kg, which equates to 87mg/kg in humans.
Some websites recommend 1mg/kg as a "safe" starting dose, but this has not been substantiated. There's also no data to support if it can burn fat, elevate energy expenditure, raise body temperature, increase performance or have any exergonic benefits for athletes.
My thoughts on DMHA
I first played around with DMHA in 2015 after receiving a sample to develop a new product. To be honest, I didn't love 1,3-DMAA (now 1,4-DMAA is a different story), so I was skeptical to try it out.
I always err on the lower dose when it comes to trying new stimulants, as I've had too many bad experiences with high doses.
I first tried 50mg of DMHA by itself and didn't notice much. After some trial and error, 100-150mg seems to be the smaller dose, where it's not too strong but still very noticeable. I will add that DMHA does have a more evident euphoric feeling compared to DMAA, and I have had great workouts using DMHA with small amounts of caffeine and nootropic compounds like CDP choline and huprazine A.
Anecdotally, the cognitive enhancement was definitely observed when I used DMHA before a lift, or even to get work/reading done.
If you are a serious stim junkie and have used DMAA before, DMHA is for you. I recommend finding a product that uses at least 100mg, along with caffeine for a nice combination of focus and energy.