Imma Perfetto
Cosmos science journalist
Australian researchers have been awarded $2.2 million to trial a stimulant medication for the treatment of withdrawal in people with methamphetamine use disorder.
If proven effective, it could become the first approved treatment in the world for methamphetamine withdrawal.
The national clinical trial will assess the potential of Lisdexamfetamine, which is already prescribed to treat ADHD and binge eating disorder in Australia, to reduce the withdrawal symptoms associated with stopping methamphetamine use.
The funding has been awarded under the National Health and Medical Research Council’s (NHMRC) Clinical Trials and Cohort Studies grant scheme.
“Withdrawal is not the treatment or cure in itself, but it is that important stepping stone for other treatment options and supports longer term,” says Dr Krista Siefried, clinical research lead and deputy director of the National Centre for Clinical Research on Emerging Drugs (NCCRED), who is involved in the research.
As a psychostimulant, methamphetamine use can produce euphoria, increase activity, and decrease appetite. It is also highly addictive, and its use is associated with increased mortality, cardiovascular disease, poor mental health, and risk of blood-borne viral infection.
Siefried says Australia has the highest prevalence of methamphetamine dependence, at about 7 times the global average.
“One of the things that happens with regular methamphetamine use is that you develop a methamphetamine use disorder … and you can actually end up having a withdrawal syndrome.”
This means that people who have developed a tolerance to methamphetamine will experience withdrawal symptoms if they abruptly stop using it.
According to Siefried, up to 97% of people who regularly use methamphetamine experience these symptoms, which can include depression, sleep issues, lethargy, and cravings for methamphetamine.
“The first step in achieving abstinence is getting through this really uncomfortable, distressing period, which is most acute within the first 7 days of ceasing methamphetamine use,” she says.
“A poorly managed methamphetamine withdrawal can be a real obstacle to achieving your treatment goals, which could include abstinence from methamphetamine use or decreasing use.”
But in their 2020 review, Siefried and collaborators found there is currently no approved medication with demonstrated efficacy for improving methamphetamine withdrawal symptoms.
To identify a candidate medication, they looked to therapies commonly used to treat withdrawal for other drugs of dependence, such as nicotine for tobacco, buprenorphine for opioids and nabiximols for cannabis.
These are agonist therapies, which work by replacing the drug being abused with an agent that acts on the body in a similar way.
The team selected a candidate agonist, Lisdexamfetamine, for a 2021 pilot study published in the journal Drug and Alcohol Dependence.
Lisdexamfetamine is a prodrug – a compound with little or no pharmacological activity itself, but which converts inside the body into the active drug dexamphetamine. As a result, its concentration in the body takes longer to peak, and peaks at a lower concentration, than when administering dexamphetamine alone.
The open-label clinical trial involved 10 adults seeking inpatient treatment for methamphetamine withdrawal, 9 of whom were men.
“We started each of them on the first day of withdrawal on a high dose of Lisdexamfetamine, 250mg, and then we tapered by 50mg [each day] over 5 days,” says Siefried.
“We found that that was safe and feasible in this population. So, we are now seeking to do this as a randomised controlled trial, where we’ll compare it against a placebo tablet amongst a randomised population.”
With NHMRC funding the team is aiming to recruit 184 people at inpatient withdrawal centres around Australia. The study has been designed in partnership with addiction medicine specialists nationally and with consumer and First Nations input.
“If we can engage people and make these first 7 days easier, there’s the potential for a better opportunity to shift into longer term treatment solutions or options later,” says Siefried.
In an interview conducted during the pilot study, a participant said: “The initial days coming off [methamphetamine are so hard]. Coming off methamphetamines takes a toll on the brain and the body. So, those first five days I think are very crucial to longer-term sobriety.
“And, yeah, my experience so far has been great. It’s put me in a more positive mindset.”
