Dexamphetamine – a restricted stimulant drug used to treat narcolepsy and Attention Deficient Hyperactivity Disorder (ADHD) – might not be as addictive as previously thought, new research from the University of Sydney suggests.

In a narrative review, published in Psychoactives, a team of researchers reviewed more than 1,700 papers to evaluate evidence underpinning dexamphetamine’s classification as a restricted drug. Surprisingly, the research team found only seven papers addressed dexamphetamine addiction directly, with only four possible individual cases of addiction detailed.

Senior author Dr Alison Poulton, Senior Lecturer in Paediatrics and Child Health at the Nepean Clinical School, said the study raises questions about the evidence underpinning its restriction by the Therapeutic Goods Administration (TGA) and the US Food and Drug Administration (FDA).

“After carrying out a comprehensive review of the available evidence, it’s surprising that we have only been able to find a handful of potential dexamphetamine addiction cases documented.

“Dexamphetamine is well-known as an effective drug in the treatment of ADHD and narcolepsy – but it is also known to have possible benefits in the treatment of other conditions including obesity, where it has the potential to be a lower-cost alternative to other drugs, such as semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro).

“It’s important that we apply scientific rigour in assessing the potential risks of pharmaceutical drugs, especially when they could have significant benefits for patients.”

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Methodology

The study was carried out by searching for relevant research on PubMed, Scopus and Embase using the keywords “dexamphetamine”, “addiction” and “dependence”. The research team looked at papers written in English, and the types of studies assessed included case reports, database audits, cohort studies, Randomised Control Trials (RCT) and systematic reviews.

History of dexamphetamine

Dexamphetamine was widely in use from the 1950s to treat conditions such as asthma, depression and a variety of psychiatric disorders, and was also found to be a useful drug for weight management.

However, in 1962 a paper published in the British Medical Journal presented evidence of dexamphetamine addiction, with psychosis and psychiatric disturbance reported in patients who had been hospitalised following large doses of the drug.

As a result, the FDA restricted the use of amphetamines, allowing them to be continued in the treatment of narcolepsy and ADHD but effectively banning them from being used in the treatment of depression, psychiatric conditions and obesity.

Next steps

To understand more about the addictive potential of dexamphetamine, the research team is carrying out a further study into the number of people being admitted to drug centres with addictions to the prescription stimulant.

Dr Poulton’s team is also carrying out a clinical trial using dexamphetamine to treat obesity. The trial will also assess whether the drug shows any addictive potential at the dosage prescribed.

First author Hazer Khalifa, a PhD candidate in the Faculty of Medicine and Health and researcher involved in the clinical trial, said: “Obesity is a major health problem that affects millions of people worldwide.

“If the clinical trial suggests that dexamphetamine can be used in the treatment of obesity without causing addiction, then it could be a significant inexpensive tool for clinicians to help people manage excess weight.”