Developed to allow soldiers to continue fighting without sleeping; now mostly used for treating ADHD, amphetamines run the gamut from methamphetamines (potent, addictive), to non-methylated amphetamines (e.g. ADHD meds such as Adderall, Vyvanse, etc), as well as drugs generally considered quite different, like MDMA (“Ecstasy”).

Let’s do a quick recap on how this class of drugs work:

• How it works: it raises dopamine (motivation, excitement) and noradrenaline (alertness, focus); with these, it creates a state of “flow”, and also suppresses hunger, fatigue, and distractions.
• How it lasts: effects last 4–14 hours, longer than cocaine or most other stimulants.
• How it’s used: ADHD is the main reason people take it; off-label and illegal use is common in competitive fields and among college students for performance—especially amongst medical students who not only study famously long hours, but are also most likely to turn to medications to ease their problems.
• How it goes wrong: in the short term, problems can include hyperfocusing on the wrong tasks, anxiety, panic, irritability, dehydration, and insomnia, as well as crashes in mood and energy afterward. In the long term, regular use can result in tolerance (i.e., a higher dose is needed for the same effect), and it can can make users feel unable to function without it. There are some possible severe side effects, namely psychosis (hallucinations, paranoia, potential schizophrenia), and cardiovascular damage (high blood pressure, heart strain, strokes, heart attacks), but these are incredibly unlikely in someone with ADHD (where the medication was merely raising neurotransmitters to “normal” levels), still very unlikely in occasional use in someone with a “normal” brain, and most likely to cause problems in someone predisposed to psychosis, mania, etc.

So, what’s this about a common antidepressant standing in for such?

From methamphetamines to mirtazapine

Meth dependence affects millions of people, and carries serious risks like paranoia, suicidality, cardiovascular disease, stroke, injury, and early death.

Now, there are currently no approved medications specifically for methamphetamine use disorder, so treatment presently relies on counselling, rehab, and other CBT approaches that simply don’t work very well for what is, after all, a physiological problem.

Some notes about mirtazapine: it’s a long-established antidepressant that is cheap, widely available, and already familiar to doctors (and, happily, off-patent). It’s a presynaptic alpha₂-adrenoreceptor antagonist, which increases central noradrenergic and serotonergic neurotransmission. That’s a lot of big words, so to translate it from sciencese a bit: it’s an “upper“, and each of those things have an indirect effect on the dopaminergic system. Yes, the same dopaminergic system that methamphetamines act directly upon.

We wrote about mirtazapine here: Norepinephrine vs Alzheimer’s Disease ← because mirtazapine is one kind of selective noradrenaline* reuptake inhibitor (SNRI)

*noradrenaline is the international name for what is called norepinephrine in the US

We also wrote about it here, too: How Much Weight Gain Do Antidepressants Cause? ← the short answer is “probably none”

Recently (published a few days ago, at time of writing), researchers (Dr. Rebecca McKetin et al.) did a large randomized, double-blind, placebo-controlled trial (the “Tina Trial”), which tested 30mg of mirtazapine daily over 12 weeks, in 339 adults with moderate to severe meth dependence.

The result, in few words, was that those taking mirtazapine reduced their meth use by 7 days out of 28.

Notably, the reduction occurred regardless of whether participants had depression, because of how the drug acts on addiction-related brain pathways, aside from just improving mood.

You can read the trial protocol here: A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial

…and the recent study results, here: Mirtazapine for Methamphetamine Use Disorder: A Randomized Clinical Trial

Want to learn more?

You might also like:

Wakefulness, Cognitive Enhancement, AND Improved Mood? ← this is about modafinil, which a) is usually prescribed for sleep disorders, though it enjoys widespread gray market off-label use, and b) works directly on the same systems as amphetamines, but purely as a reuptake inhibitor, giving it a much better safety profile, since it is less about increasing your neurotransmitter levels as high as possible, and more about not letting them sink beneath a certain level.

Take care!