The movie limitless is famous for its depiction of a fictional drug that astoundingly improves the mental capacity of the user and allows them to drastically improve their quality of life. It appeals to a certain, potentially subconscious, excitement we have for future developments in technology, and how neuroscience and pharmacology could enhance our mental abilities.
Just to be clear, there is no drug available that even closely resembles the properties of the limitless drug, which is called NZT-48. However after rewatching this movie recently I’ve been fascinated by comparing this drug to commonly used nootropics, which are cognitive enhancing drugs or supplements, and seeing which one is the closest or most similar.
To determine this it’s important to elucidate the exact properties of NZT-48.
The first property is perfect recall.
The drug enhances a person’s recall memory to a point where they can recall every single memory from their lifetime without being overwhelmed. This characteristic MAY exist naturally, with people with eidetic memories (often know as photographic memory), particularly in children, however the key difference is these people often are overwhelmed as perfect recollection of bad or traumatic memories can lead to anxiety and depression, whereas in the movie NZT-48 allowed perfect recall to be selective to memories that improved the quality of life.
Next, Instant learning and analysis.
The drug allows you to gather knowledge and understand it rapidly, allowing you to make perfectly informed decisions, making it easy to succeed at any task faced. This also allows the person to learn a skill quickly, and master it not long after. In the movie this was investing.
Lastly, Multitasking.
The drug allows you to perform multiple tasks at the same time, with the performance of one not taking away from the quality of the other. Simply put you can perform multiple tasks at a high level at the same time.
There are other noticeable qualities such as an improvement in charasima and omnilingualism which means gaining fluency in multiple languages quickly, however these traits mostly bleed into the main three mentioned before, and as ill discuss later involve the same neurological processes and parts of the brain.
Examination of existing treatments
Recall Memory:
Drugs used in the treatment of Alzheimer’s disease are called Acetylcholinesterase inhibitors, and as you’d expect help treat memory deficits. These drugs prevent an enzyme called acetylcholinesterase from breaking down neurotransmitter Acetylcholine in the brain, leading to improved communication between nerve cells.
One of the drugs, Galantamine, does this as well as increases the cholinergic neurons to Acetylcholine, making it the most efficient. However this drug has severe side effects and is not well tolerated. In this regard Donepezil will be the most similar, and it has been shown to also improve REM sleep therefore leading to even more improvements of recall memory.
Other notable compounds include Nicotine, Alpha GPC, Caffeine, and Dexamphetamines.
Instant learning and analysis:
As you can imagine, the relevant cognitive function the drug needs to improve is concentration concentration, as well as some fringe benefits. As you probably can guess, the drug is going to be a stimulant which acts on the central nervous system to improve alertness and attention. There are 4 main drugs, Adderall (which is a dextroamphetamine and amphetamine mixture) or Dexedrine (which is just dextroamphetamine), Modafinil, and Methylphenidate (drug name Ritalin).
Without getting too in depth, Dextroamphetamines and Modafinil are considered the most potent in this regard, and commonly used recreationally to improve productivity and to learn new skills.
Let’s compare the two.
Direct vs. Indirect effects: Dextroamphetamine directly increases dopamine and norepinephrine (known as adrenaline) levels through multiple mechanisms, while modafinil primarily affects dopamine levels directly and influences serotonin indirectly. Modafinil may also influence Orexin which is involved in circadian patterns, to produce a wakeful feeling constantly throughout the day but this does not improve concentration rather it just prevents feelings of tiredness.
Because of this Dextroamphetamines like Dexedrine and pretty much Adderall too are the drugs that most closely mimic NZT-48’s instant learning and analysis effect. To pick between the two of them I did some research and found a nootropics data analysis, which surveyed ~2000 people in an enthusiastic nootropics community, to rank nootropics 1-10, with 10 being life changing.
Sure enough both compounds ranked as the top two, with Dexedrine a close top spot. Now it needs to be stated, when it comes to dosing stimulants there it is theorised, but at this point very well accepted a inverted U shaped curve of performance. Anyone with a prescription for ADHD stimulants can attest to this. This is something I noticed personally with my adderall prescription.
If dosage exceeds a certain point it can cause excitotoxicity which leads to apoptosis (which means death), overstimulation, anxiety and more. Its very common for jet fighters to use Dexedrine, and allegedly it used to be prescribed to jet fighters in some countries.
Finally, nootropics which enhance multitasking:
Multitasking is one of the more difficult things to understand, but essentially two main components of it are ‘executive functions’ and ‘working memory capacity’.
Funnily enough, both ADHD-stimulants and Modafinil are both well known to improve both aspects.
Methylphenidate was mentioned in a recent meta-analysis as a well studied improver of executive functions. Speculatively, I believe that Methylphenidate is not superior to Dextroamphetamines/Amphetamines in this regard, and they have just been specifically studied more in this regard. The reason I believe this is because Dextroamphetamines/Amphetamines have been shown to outperform Methylphenidate in the treatment of ADHD.
Overall the closest thing to the drug seen in Limitless is called Dexedrine. However I’d like to speculate that a tablet containing both Dexedrine and Donepezil (in lower dosages) would be the closest thing to the limitless drug, however no such drug exists. There are a few reasons for this, number one
Donepezil is also a sigma 1 agonist as well as an acetylcholinesterase inhibitor, meaning it will enhance the effect of amphetamines which means you will need less amphetamine to induce a similar effect which leads into … Number 2, by splitting the amount of dextroamphetamine you consume in half you reduce the excitotoxicity of neurons in your brain, AND ensures your neurons don’t down regulate your receptors, which means you develop less tolerance to the drug and decrease side effects.
EXTRA
Piracetam:
Piracetam has been examined in a number of clinical trials for the treatment of ADHD, with a 2008 clinical trial titled ‘Atomoxetine and piracetam in the treatment of attention deficit hyperactivity disorder in children’ concluding the combination of piracetam and atomoxetine (Strattera) was more effective than atomoxetine (Strattera) alone.
https://pubmed.ncbi.nlm.nih.gov/18833117/
Its important to note that Strattera and Amphetamines, although are both used to treat ADHD, are completely different compounds. But Piracetam is so important to mention when it comes to this topic because it seems to enhance many other compounds, particularly those which interact with the acetylcholine system.
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