In September 2021, the National Institute on Drug Abuse (NIDA) and the National Institutes of Health (NIH) released a report with a shocking headline:
Here’s how NIDA Director Nora Volkow, MD, describes this development in the overdose crisis in the U.S.:
“We are in the midst of an overdose crisis in the United States, and this tragic trajectory goes far beyond an opioid epidemic…public health approaches must be tailored to address methamphetamine use across the diverse communities at risk.”
Most people know about the opioid overdose crisis. Now in its third decade, the crisis has claimed the lives of over a million people, and the number is still growing. The crisis has occurred in three waves. The first wave began in the late 1990s, driven by an increase in opioid prescriptions for pain. The second wave started around 2007, driven by people who developed opioid use disorder (OUD) as a result of prescription medication, and turned to dangerous illicit opioids. The third wave started around 2013, driven by the increasing presence of fentanyl in drugs of misuse and disordered use.
We’re now in what experts call the fourth wave, which began around 2019.
This wave is driven by polysubstance misuse, the COVID-19 pandemic, and an increase in co-occurring mental health disorders. One of the primary substances involved in fatal overdose – one component of the poly aspect of this phase – is methamphetamine.
For people who have never heard of methamphetamine, it’s a powerful synthetic stimulant developed in laboratories in the early 20th century. It’s characterized by its extreme potency, which causes increased energy and feelings of euphoria. Compared to typical amphetamine, methamphetamine reaches the brain in larger amounts per dose, has a longer duration of action, and causes significantly greater harm to the central nervous system. In addition, drug traffickers often add fentanyl to methamphetamine to increase volume, which complicates the situation.
For details on how fentanyl contributes to the overdose crisis, please read this article on the blog section of our website:
For the purposes of this article, we’ll shift our focus to methamphetamine, and discuss a recent publication called “Bupropion and Naltrexone in Methamphetamine Use Disorder.”
Overdose Crisis Facts and Figures: The Addition of Methamphetamine Use Disorder
First, let’s get on the same page with regards to our awareness of the overdose crisis in the U.S. Data from the Centers for Disease Control (CDC) shows the following for the years 2019-2021:
- 2019: 67,697 overdose deaths
- 2020: 78,056 overdose deaths
- 2021: 107,622 overdose death
That’s the overall data. Those numbers are why the overdose crisis makes headlines: the situation is dire, and despite the best efforts of substance use disorder (SUD) treatment providers and local, state, and federal officials and policymakers, the numbers continue to increase every year. That’s why we write articles like these: we know treatment for SUD works, but we need to reach as many people as possible to give them the lifesaving support they need.
The data in the NIDA report on methamphetamine we cite above shows the following:
- In 2015: 5,526 people died of stimulant overdose
- In 2019: 15,489 people died of stimulant overdose
That’s an increase of 180 percent.
Over the same period, NIDA/NIH data shows:
- Methamphetamine increased by 43%
- Frequent methamphetamine use increased by 66%
- Combined methamphetamine and cocaine use increased by 60%
Further, NIDA/NIH data indicates alarming changes in methamphetamine use patterns:
- Prevalence rates quadrupled for people ages 18-23
- Rates tripled among women
- Rates doubled among straight men
- Prevalence increased most rapidly among Native Americans and African Americans
- Prevalence of intravenous injection increased
- Injection rates increased most significantly among gay men
These increased rates overall, and increased rates among vulnerable populations, creates significant concern among both treatment professionals and public health officials. While the crisis in opioid use, misuse, disordered use, and overdose led to a nationwide effort to mitigate the harm cause by the crisis, the response to the increase in methamphetamine use is in its nascent stages.
Working to Address Methamphetamine Misuse and Methamphetamine Addiction
Here’s how Dr. Emily Einstein, head of the Science Policy Branch at NIDA, describes our current predicament with regards to methamphetamine use, misuse, and methamphetamine -related overdose fatality:
“What makes these data even more devastating is that currently, there are no approved medications to treat methamphetamine use disorder. NIDA is working to develop new treatment approaches, including safe and effective medications urgently needed to slow the increase in methamphetamine use, overdoses, and related deaths.”
This is the precise reason the study we mention at the beginning of this article – Bupropion and Naltrexone in Methamphetamine Use Disorder – is important. The study seeks to identity “safe and effective medications” to address the role of methamphetamine in the ongoing overdose crisis.
Let’s take a look at how researchers conducted the study, and then discuss their results.
First, the why and how of the process.
The broad context of this study, and its clinical justification, is that medication-assisted treatment (MAT) is considered the gold-standard therapeutic approach for people who meet the clinical criteria for opioid use disorder (OUD).
MAT for OUD involves the medications buprenorphine, methadone, or naltrexone. This potential MAT therapy for methamphetamine use disorder involved two medications. One is in regular use, and the other is typically used as an antidepressant:
- This medication blocks the action of opioids in the brain. It’s used opioid use disorder, and also for alcohol use disorder. Its success in those contexts, and its actions in brain areas related to non-opioid addiction, make it a viable candidate for treating methamphetamine use disorder.
- This medication is an antidepressant that has properties similar to amphetamines. Previous research shows that it affects the two chemical messengers in the brain associated with addiction, norepinephrine and dopamine. Researchers theorize that it may reduce symptoms associated symptoms related to methamphetamine withdrawal, and therefore, reduce rates of relapse and/or continued methamphetamine misuse.
Researchers recruited 403 adults ages 18-65 with a stated desire to stop or reduce their methamphetamine use. Participants also met the following criteria:
- Diagnosed with moderate or severe stimulant use disorder (methamphetamine type)
- Reported methamphetamine use on at least 18 days in the month before the study began
- Tested positive for methamphetamine at least twice in the ten days before the study began
- Tested negative for opioids before the study began
Th research team randomly divided the participants into two groups: an experimental group and one placebo group. Scientists call this process randomization. In a randomized trial, neither researcher nor participants knows who is in which group.
Participants then entered the experimental phase of the study, which took place in two stages of six week each. During the study, researchers defined a positive response to the experimental treatment as:
- Three negative urine screens out of four at the end of stage one
- Three negative urine screens out of four at the end of stage two
- The ¾ metric was applied to both stages, rather than a 6/8 overall metric, because of the rerandomization after Stage 1
Here’s what happened during the experimental phase:
- Intramuscular injection of extended-release naltrexone or placebo once every 3 weeks
- Administration of extended-release oral bupropion tablets once a week
- Urine screens for presence of methamphetamine administered twice a week
After the first six weeks, study participants were rerandomized – that’s exactly what it sounds like – and then participated in the same process for another six weeks.
MAT for Methamphetamine Use Disorder: The Results
Fair warning: the results of this study show promise but were relatively underwhelming.
Here’s what happened during Stage 1:
- 16.5% of the experimental group showed a positive response
- 3.4% of the placebo group showed a positive response
- Overall effect, stage 1: 13.1%
And here’s what happened in Stage 2:
- 11.4% of the experimental group showed a positive response
- 1.8% of the placebo group showed a positive response
- Overall effect, stage 2: 9.6%
Based on these figures, researchers determined the overall treatment effect, after combining data from both stages, as follows:
- 13.6% of experimental group participants showed a positive response
- 2.5% of placebo group participants showed a positive response
The research team reported additional data. Among participants who provided all four samples in the last two weeks of each stage:
- 28.8% in the experimental group showed positive response
- 5.1% in the placebo group
- 16.2% in the experimental group showed positive response
- 1.3% in the placebo group
As we mention above, these results show that MAT with bupropion and naltrexone – in this context, dosage, and combination – show promise, but do not meet the threshold for positive response as seen in MAT for opioid use disorder (OUD) with buprenorphine, methadone, or naltrexone. Therefore, this study is not a game-changer. However, among participants who provided all four drug screen samples in the last four weeks of stage 1, close to 30 percent showed a positive treatment response.
Given the increase in fatal methamphetamine-related overdose identified since 2015, that result is encouraging. It’s reason to be optimistic and believe that effective MAT for methamphetamine use disorder is within reach. And for those participants for whom the treatment worked, that is a game-changing, life-changing – and for some – a lifesaving outcome.
Here’s how the study authors describe their findings:
“In persons with moderate or severe methamphetamine use disorder, treatment with the combination of extended-release injectable naltrexone and daily oral extended-release bupropion over a period of 12 weeks resulted in a higher response than placebo.”
That’s the way a research scientist says this therapeutic approach worked for some, but not for most. Our goal is to help as many people as possible move past the harmful cycles of methamphetamine addiction. We’ll keep a positive attitude and a close eye on this research. If and when this technique is ready, and these medications gain approval by the Food and Drug Administration (FDA) for use in this context, we’ll consider using them for our patients.
Until then, we hold out hope for the future, which itself is an essential component of treatment and recovery from any substance use disorder, including methamphetamine use disorder.