What’s the latest on stimulant replacement treatment?
Many people who are dependent on illicit opioids (such as heroin) have benefited from the Opioid Treatment Program (OTP), which allows them to be prescribed a ‘substitute’ opioid such as methadone or buprenorphine. A replacement program like that for people who use stimulants (such as methamphetamine) doesn’t exist. However, some promising research into possible stimulant replacement treatment is happening.
Maureen Steele, a Peer Worker who is currently helping design a trial exploring the use of psychedelics in the treatment of “methamphetamine use disorder”, told Users News: “the idea of treating meth use disorder by substituting/replacing meth for another drug is unfortunately not well studied. There are a few options that have been studied around the world, but none have been convincing enough so far to be included in the guidelines for clinicians.
“A review of research into pharmacological treatments for methamphetamine/ amphetamine dependence published in 2020 said no pharmacotherapy option yielded convincing results for the treatment of dependence.
“However, several drugs — including stimulant agonist treatments such as dexamphetamine and methylphenidate — did warrant further investigation in larger scale studies.
“Since 2020, Australian studies have been looking at prescribing lisdexamphetamine (lisdex) as a substitute for meth.
“The LiMA (lisdexamphetamine for the treatment of methamphetamine dependence) study is testing if a high dosage of lisdex over a period of multiple weeks is effective in reducing meth use, cravings and withdrawal symptoms. The results should be published soon.
“Another smaller trial is looking at using lisdex to help with managing withdrawals from meth. This trial is about seeing whether people can go into an inpatient withdrawal centre, stop using meth, be given high dose of lisdex, and then reduce the dose to nothing over the course of 5 days. The results have just been published, but because it was a small trial, more research will likely be needed before it is a widely available treatment.
“Unfortunately, because there is still a lack of published evidence, most doctors and psychiatrists are still unlikely to prescribe you lisdex or dexamphetamine (dex) — even though they are allowed to prescribe these to people with ADHD (attention-deficit/ hyperactivity disorder).”
Lisdex trial
Liam Acheson, Research Officer at St Vincent’s Hospital, Sydney, and a PhD candidate at the National Centre for Clinical Research on Emerging Drugs (NCCRED) was a lead researcher on the lisdex clinical trial, which was conducted in an inpatient withdrawal management unit at St. Vincent’s Hospital Sydney, Australia. He explained to Users News what it was about.
We are looking into how a stimulant medication called lisdexamphetamine (lisdex) could be used to help people withdraw from methamphetamine (meth).
‘Withdrawal’ is what happens when you stop or reduce use. When you’ve regularly used a high amount of a drug over a long period of time, you develop a tolerance—your body gets used to it and you need more and more to get the same effect. If you use less than your usual amount, your body and mind will start to crave it.
Withdrawal is awful. The first week or so of withdrawal is called the ‘acute’ phase, and it is when you will be feeling the negative symptoms in your body.
The easiest way to get rid of withdrawals is to start using again. Getting through that first intense week is a barrier that stops a lot of people from moving with their life and with their goals to reduce use or be abstinent.
Lisdex is very similar to meth — they’re both amphetamines — and our study hopes to show that by replacing meth with lisdex, it will help make those withdrawal symptoms more manageable.
Helping people get through the first week helps people get to where they want to go. It’s a harm reduction approach, rather than abstinence.
Some participants wanted to stop using entirely, and others wanted to just have break, or reduce their use so they could regain some control and change their use patterns. We were only including people who wanted to go through withdrawal. The goal of that withdrawal was up to them.
How did the trial work?
We had 10 people participate in our trial — we wanted more, but COVID forced us to only do a small trial. We had each participant come in during a different time of the year — they didn’t get to meet each other.
We had people come and stay fulltime for 5-7 days at St Vincent’s Hospital Gorman Unit, which is a medically supervised “in-patient” space for short stay withdrawal from alcohol and other drugs.
On day zero, the participant rocks ups between 9am-3pm. They generally would have used meth within the last 12 hours. When they wake up on day 1, we dose them in the morning, because lisdex lasts a while and we don’t want to keep them up all night. We start them on 250mg of lisdex.
The first dose is 3 times higher than the maximum approved dose you can give someone for ADHD. We are using a higher dose because our participants have a high tolerance.
On day 2, we give 200mg, and then each day we reduce the dose by 50mg until they get 50mg on day 5. Then on day 6 and 7 they get no dose, but are allowed to stay at our clinic, or just leave. Many people stayed so they could have more support to deal with the “rebound withdrawal” that happens when they stop using lisdex.
The aim is just to get them through the acute symptoms of the first 5 days. The aim is not to provide lisdex as a long-term replacement for meth. That approach is being trialed in another study called “LIMA”. My study’s approach may not end up being the perfect approach, but it is the approach we were able to run! And I also don’t believe one approach will work best for everyone — we will probably end up needing a variety of options for people to choose.
The results
The results were really promising.
Overall, people rated treatment highly. Withdrawal symptoms and cravings fell rapidly and remained low even after people were discharged.
The amount of “adverse events” reported was also lower than if people had withdrawn without the help of lisdex. We only recorded 17 adverse events and they were all minor side effects, such as headaches, upset tummy, and everyone got better without needing any extra support. No-one needed to leave the trial early, and no-one refused a dose. This shows that it is really safe.
Before I go on, remember: Not every client's goal was abstinence.
Some people had never experienced withdrawal before. Others had tried to stop, or stopped before, and had experienced withdrawal.
People described positive personal effects from lisdex, especially people who had previously tried to withdraw. Normally people crashed and burned and would sleep for 3 days. With lisdex, people had enough energy, focus and wellbeing to be able to do normal things during the day and still get a good long sleep at night. They were shocked how effective it was: they remarked about lack of cravings, how it make them feel normal, have an appetite, and be socially active. One person even said they were able to focus on reading a book for the best time in years!
The downside of having people stay in the facility was that some people missed home and missed family — though this time alone was also what some people wanted.
Follow up — How did participants go afterwards?
After discharge, we had follow up interviews with clients once per week for 3 weeks.
Of the 8 people who completed our follow up, 4 reported abstinence for the full follow up period. This was really amazing for some of them, who had not been able to achieve abstinence prior!
One really interesting finding was that 2 clients were abstinent during week 1, then used meth during week 2, but were abstinent in week 3. They both had goals to be abstinent, so they were proud of being able to not use, relapse and then stop again before it became regular.
The 2 people we didn’t follow up with left the unit before the end of treatment. They didn’t leave because of not being able to cope with withdrawal or lisdex. Rather, one had to go to court and the other had trauma from incarceration, and being in the withdrawal unit was retraumatising. These are important issues that future studies and treatments will need to adapt to.
1 person wanted to use the trial to take a break from meth so he could get back in control of his use and use lower doses in future.