Review
Have prohibition policies made the wrong decision? A critical review of studies investigating the effects of DMAA

https://doi.org/10.1016/j.drugpo.2016.10.005Get rights and content

Abstract

In June 2012 DMAA (1,3-dimethylamylamine), an ephedrine-like vasoconstricting substance which had been included in many popular sports supplements, became a scheduled substance in Australia, following bans in several other countries. The underlying rationale for this ban was that DMAA use is unsafe. This paper aimed to critically review the available evidence on the acute and/or long-term harms of DMAA. Using five research databases (PubMed, Embase, ProQuest Health and Medical Complete, and Web of Science) and the key terms ‘methylhexaneamine’, ‘DMAA’, ‘dimethylamylamine’, ‘1,3-dimethylpentylamine’ and ‘2-amino-4-methylhexane’, 842 articles were identified once duplicates removed. Sixteen studies met the inclusion criteria and were included in the review. Of the included studies, eight were case studies, which reported on eight patients who presented to emergence departments. All were retrospective in their reporting. The patients displayed various outcomes; while the patients were presenting with serious problems, in most patients conditions subsided on cessation of supplement use. The remaining eight experimental studies were low powered, with a number of studies conducted by a single research group with industry ties, and broadly investigated the effects of DMAA on physiological outcomes. Mixed findings were apparent, although escalations of blood pressure were present on acute dosing, as well as decreases in measures of body weight and body fat. There is a shallow evidence base describing the adverse effects of DMAA and the dose above which such effects may occur. The scheduling of DMAA in many countries may now impede research efforts to determine whether there are safe doses at which DMAA can be consumed.

Introduction

DMAA (1,3-dymethylamylamine; methylhexaneamine) is a pharmaceutical derivative first introduced in 1948 as a nasal inhaler for the alleviation of irritation and inflammation of the mucous membrane inside the nose. Approval for the substance was withdrawn in the 1970s (Cohen, 2012), as its medical efficacy was brought into question. DMAA has more recently been used in a variety of popular sports supplements such as Jack3d® under the guise of being a naturally occurring substance. One study had suggested that DMAA was found in geranium oil (Ping, Jun, & Qing, 1996) however, recent studies have found little evidence for this suggestion (Lisi, Hasick, Kazlauskas, & Goebel, 2011). DMAA has been touted as ‘safe’; despite this, it has been banned in several countries as well as by the World Anti-Doping Agency (WADA) because of suggestions it could enhance performance as well as pose a health threat. To date, however, there has been little discussion regarding the evidence behind these policy decisions, nor of the quality of the evidence informing them.

DMAA is a stimulant which shares broad structural similarities with amphetamine. A review by Venhuis and de Kaste (2012) identified several animal studies from the 1940s and 1950s indicating that DMAA has similar effects as ephedrine and amphetamine, including an increase in arterial blood pressure, vasoconstriction, tachycardia, and bronchodialation. DMAA, under the name methylhexaneamine, was placed on WADA’s list of prohibited substances from 2010 (World Anti-Doping Agency, 2009) and has since caused controversy, with athletes from several countries testing positive for its presence. In 2010, nine Australian athletes tested positive, and at the time it was thought that this had occurred inadvertently due to the substance’s inclusion in many sports supplements (Australian Associated Press, 2010). DMAA has been implicated in causing more serious adverse health consequences. DMAA was identified in the toxicology reports of two United States Army soldiers who died in 2011 (Tritten, 2011). Further, a New Zealand man who ingested ‘party pills’ containing DMAA suffered from a cerebral haemorrhage (Gee, Jackson, & Easton, 2010).

DMAA was banned in Canada in 2011, and has since been banned or heavily restricted in other countries including New Zealand (banned in 2012) and the United States (illegal to market as a dietary supplement). Prior to 2012, DMAA was not a scheduled substance in Australia. In June 2012, the Advisory Committee on Medicines Scheduling proposed including DMAA in Schedule 9 (‘Prohibited Substances’) of the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP). Six pre-meeting submissions were received; of these, five were against the prohibition (Therapeutic Goods Association, 2012). The Therapeutic Goods Association (TGA) ultimately included DMAA in Appendix C of the SUSMP, noting that DMAA has no current accepted therapeutic use; a stimulant effect which can include psychoactive effects; that the substance was actively promoted as a ‘party drug’ as well as a sports supplement; and that a number of significant adverse events had been reported due to the use of DMAA (Therapeutic Goods Association, 2012). Given this decision, sports supplements that contained DMAA were also banned.

Anecdotal evidence and case studies aside, DMAA as a sports supplement has been promoted as ‘safe’; indeed, some of the submissions to the TGA suggested that there was no conclusive link between DMAA and negative health effects. DMAA was also marketed as a ‘legal high’ in New Zealand prior to its ban, and it is now considered a novel psychoactive substance. Given the variety of divergent information relating to this substance, the aim of this review was to search, synthesise, and critically review the literature surrounding the health effects of DMAA.

Section snippets

Method

A systematic search was undertaken to identify relevant articles. Key search terms ‘methylhexaneamine’, ‘DMAA’, ‘dimethylamylamine’, ‘1,3-dimethylpentylamine’ and ‘2-amino-4-methylhexane’ were applied using four research databases (PubMed, Embase, ProQuest Health and Medical Complete, and Web of Science). The searches were conducted in October 2015. The author reviewed titles and abstracts of articles published in English to identify studies which reported on the health effects of DMAA. The

Selection of studies

The search found 1462 articles results, of which 842 remained after duplicates were removed. Eight hundred and three articles were discarded based in title and abstract; 39 articles were identified for possible inclusion based on title and/or abstract and were read in full. A further 23 were discarded for not meeting the inclusion criteria. The flow diagram in Fig. 1 depicts the search strategy and the number of articles considered at each stage.

Description of the studies

A description of the studies are in Table 1 (case

Discussion

DMAA has been banned by the World Anti-Doping Agency and various national governments because of the potential for harm. This review sought to collate the available human evidence regarding the acute and chronic effects of DMAA, to examine whether this ban is evidence-based. The findings suggest that the volume of evidence available is not large, with only 16 studies meeting the inclusion criteria. Half of the included studies were case studies reporting on patients admitted to emergency

Conclusions

There is a limited evidence base describing the adverse effects of DMAA. The volume of evidence surrounding DMAA is small, with most experimental studies utilizing less rigorous designs. While the studies highlight that there are severe adverse effects which can be experienced, it is unclear how prevalent these are, and whether they are actually related to DMAA use. They also serve to show that all substances have the potential to cause harm. The scheduling of DMAA in many countries may now

Acknowledgements

The author would like to thank Drs Raimondo Bruno, Melissa Graham, and Fiona Andrews for comments on previous drafts. No funding was received for this study.
Conflict of interest

The author reports no conflict of interest. No funding was received for this study.

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