Australasian Science: Australia's authority on science since 1938

The Dope on DMAA

By Ian Musgrave

DMAA is found in many weight loss and performance enhancement supplements, but it has now been classified by the TGA as a prohibited substance with no therapeutic potential.

The Therapeutic Goods Administration (TGA) has considered a proposal to list 1,3-dimethylamylamine (DMAA) as a schedule 9 compound. Schedule 9 compounds are prohibited substances which have no therapeutic potential, for example Heroin (although there is the possibility of therapeutic use for this drug).

The TGA has now made a ruling, announced today, and placed DMAA in appendix C of the scheduled drug list.

Well, that’s all very nice, but what is DMAA and why on Earth should I care

Well, it’s obvious you are not a body builder.

DMAA vs Amphetamine structure Ian Musgrave, visulaised in Jmol

DMAA is an aliphatic amine which looks a bit like amphetamine. Although it is a stimulant, it is not clear if DMAA actually works like amphetamine. DMAA was introduced as a nasal decongestant by Eli Lilly in 1948, but was withdrawn in the 1970’s.

DMAA was reintroduced as a natural supplement, based on it’s alleged presence in Geranium extracts. However, it turns out Geraniums have no DMAA in them, and all DMAA in supplements and pills would appear to be synthetic.

The sports and dietary supplement industry put it in various preparations for weight loss and performance enhancement. DMAA seems to be used most in pre-workout supplements, although recently DMAA has been in use as a party drug. The party drug use was a significant concern in the TGA’s deliberation.

The supplement users reacted with some incredulity (and a lot of stockpiling) to the impending ban on DMAA. DMAA is banned by most sporting bodies for use by athletes, but that is because it is a stimulant, and stimulants in general are banned by sporting bodies. Is DMAA really as bad as Heroin?

With the recent ruling, it appears the TGA thinks DMAA is as bad as Borage.

What, Borage, the herb?

Yes, borage (suspected hepatotoxicity).

Oh come on, it looks like amphetamine, it’s got to be bad surely

Merely looking like another compound is no guarantee that something will have the same properties as that compound, as drug companies have learnt to their cost, even small changes in structure can have big effects on how fast a substance breaks down, or activates biochemical pathways.

Data on the potency and mechanism of action of DMAA is hard to come by. You have to go wayback in time to find some of this data. For example The Dispensatory of the United States of America 1950 Edition, reports that DMAA’s systemic toxic effects in animals were “greater than that of ephedrine and less than that of amphetamine,” .

Experimental administration of DMAA to humans at levels consistent with supplement use, alone, or together with caffeine (which is in a lot of DMAA containing supplements), shows DMAA can cause a modest increase in blood pressure taken as a one off dose. If you take it for 10 days or more blood pressure appears to return to normal (doi: 10.4137/NMI.S8568, doi: 10.4137/NMI.S8885).

Outside of these controlled experiments DMAA has been associated with a number of adverse events, such as panic attacks, seizures, stress-induced cardiomyopathy, and is suspected to be involved in two deaths. While these reports are consistent with the known pharmacological effects of DMAA, causation has not been established in these cases, especially as DMAA is often consumed with high doses of caffeine, which has also been associated with similar adverse effects.

However, in New Zealand, consumption of DMAA as a party drug has been associated with a case of cerebral hemorrhage. It is almost certainly the use of DMAA as a party drug that has the TGA most worried.

What we also don’t know is how frequent these adverse events are (again, this assumes that DMAA is the only culprit in theses events, the caffeine may also contribute in the events associated with supplements).

Given the relatively few reported events and the widespread use of these supplements, we might suspect the frequency is low. But we also know that adverse events are under-reported, and the exact number (or even ball-park number) of users is unclear.

So the extent of physical harm caused by DMAA is uncertain, although probably less than for amphetamine if we go by emergency admissions. The addictive potential of DMAA is not known, but is also probably less than that of amphetamine.

Sounds like we should treat it like amphetamine

Well, if we are to consider it to be exactly the same as amphetamine, then the appropriate schedule would be schedule 8, not 9. However, it is extremely unlikely that DMAA is equivalent to amphetamine. This was the approach taken in today’s TGA ruling.

So what would be appropriate? Caffeine is used in a similar way in supplements, and in energy drinks is associated with a similar spectrum of harms to DMAA with at least one reported death, should the TGA have treated DMAA like caffeine?

Classification of any drug must balance benefits and harms. Making body-builders feel as if they have more energy is not much of a benefit when compared to even a small possibility of cardiomyopathy and other cardiovascular harms.

Ironically, it seems DMAA may not be much of a performance booster, at least, it doesn’t improve running performance. We have no empirical evidence other than testimonials that DMAA improves anything else, it may just be a placebo.

And the use of DMAA as a party drug, where very large amounts may be taken increasing the likely hood of serious cardiovascular harm or death, is the real worry. On the other hand, treating a mild stimulant as if it were as harmful as heroin was an overreaction.

So what is this appendix C classification?

It’s for drugs and chemicals that can be harmful but not so harmful as to warrant listing as schedule 9. This listing is acknowledges that DMAA is not as harmful as heroin, but still harmful enough to remove it from use.

I used the example of Borage before. Borage is a herb that was used as a herbal medicine, but it caused liver damage. Now it is illegal to make herbal medicines that contain Borage. On the other hand no none has ever been busted for having Borage growing in their backyard, whereas growing opium poppies would get you in trouble quick smart.

Body builders will be annoyed, but it is very hard to argue that making body builders feel like they have more energy outweighs preventing harmful DMAA use, cerebral hemorrhage is a terrible price to pay for a party drug buzz.

So what will bodybuilders do for stimulants now?

They already take bucket-loads of caffeine, it’s doubtful they need more.

Speaking of Caffeine, shall I fire up the espresso machine?

Certainly!

his article was originally published at The Conversation.