Pharmacies of the Future: Chemical Lego Towers

Chemists and engineers are in the process of making on-demand production of pharmaceuticals less of an idea from a movie, and potentially a viable option for situations where medicines may not be easily accessible.

Imagine taking a vacation to an isolated rainforest resort.  You explored your adventurous side, hiking through the lush vegetation with a knowledgeable tour. Less than 10 minutes after arriving back at the hotel, an uncontrollable itch began on your forearms. It traveled up your arms, across your chest, and began rising up your neck. Was it from a bug or a plant you encountered during the hike? At this point, you are unconcerned about the cause, and just want a solution. The closest drug store is hours away; when booking the trip, it seemed like a great idea to pick the most isolated resort for your dream vacation. Even if the drug store was closer, it was not a guarantee that they would even have anything to help you. In the US, there were over 200 instances of drugs shortages from the years 2011-2014. There was no telling how difficult it would be to get medicine to this remote location.

You head to the front desk of the hotel, hoping they have something to give you for relief. They lead you down the hall and into a small room. There are a few chairs and an appliance that is similar in size and shape to a refrigerator. The employee enters a few commands into a keyboard and the machine starts working. In fifteen minutes, the employee hands you two tablets- diphenhydramine hydrochloride, more commonly known as Benadryl®.  

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Diphenhydramine, better known by the brand name Benadryl, is one of the four medications that can be synthesized by the original compact, reconfigurable pharmaceutical production system.

While this scenario is not plausible in the current day, it will be in the near future. In a 2016 Science article, researchers from around the world introduced a refrigerator-sized machine that could make four common medicines. More recently, a 2nd generation prototype was released; the new model is 25% smaller and contains enhanced features necessary for the synthesis of four additional drugs that meet US Pharmacopeia standards. This is possible by technology known as flow chemistry. Flow chemistry is a development where chemicals are pumped through tiny tubes. When two tubes merge, a reaction between the two chemicals occurs, resulting in a new molecule. Compared to traditional chemical reactions (stirring two chemicals together in a flask), flow reactions are generally safer and happen faster.

In this new machine, there are different “synthesis modules,” or small boxes that contain the equipment to do a single chemical reaction. Much like an assembly line to build a car, pharmaceutical molecules are made by starting with something very simple, and pieces are added on and manipulated until it is something useful. In the case of pharmaceuticals, the assembly line consists of molecules and reactions. The modules, or boxes, can be rearranged to do the chemical reactions in the order needed to make the desired medicine. To make a different medicine, the modules must simply be rearranged. Researchers can use the original prototype to make Benadryl, Lidocaine (local anesthetic), Valium (anti-anxiety), and Prozac (anti-depressant), using different combinations of the exact same modules. As of July 2018, the FDA reported that both diazepam (Valium) and lidocaine were currently in a shortage, due to manufacturing delays.

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On demand pharmaceutical production would allow access to medicines in rural locations and war zones.

The future of this technology would allow anyone to use it. A user could simply input the medicine they want, and computers would rearrange the modules and use the correct starting chemicals, and in about 15 minutes, you could receive the desired medicine. This technology has vast applications. It could help alleviate the aforementioned drug shortages. Additionally, it could allow access to medicine in locations where it may be difficult to ship to, including rural locations or war zones, often places that need medicines most. In these places, delivery may be difficult, and some medicines go bad quickly. With this technology, it would not be necessary to store medicines that could go bad; it could simply be made as soon as it is needed. This could also prevent waste from medicines that are not used before they go out of date. These developments could revolutionize the pharmaceutical industry and I look forward to seeing the good that these technology advances can lead to. 

Peer edited by Nicholas Martinez

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A Stimulating Treatment for Drug Addiction

Drug addiction is notoriously difficult to treat. Limited treatment options are available for those suffering from addiction, including behavioral therapy, rehabilitation programs, and medication. However, current drug addiction medications are only approved to treat opioid, tobacco, or alcohol abuse, leaving out many other drugs of abuse,such as cocaine or methamphetamine.

Yet even when patients successfully complete rehab or stick to a medication plan, there is still a risk of relapse. This can often be due to the emergence of drug cravings. For instance, a former alcoholic may see a sign for a bar they used to frequent. That sign can induce feelings of craving for alcohol, even long after the user quits or abstains from drinking. Strong cravings could lead to a relapse and a resumption of the cycle of addiction.  

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No pharmaceutical treatments are currently available for cocaine addiction.

However, a recent discovery may change the way we approach drug addiction treatment. Italian researchers, working alongside the National Institute on Drug Abuse (NIDA), were able to reduce drug cravings and usage in cocaine addicts for the first time using a technique called transcranial magnetic stimulation (TMS).

Long-term use of drugs change how brain cells communicate to each other. Think of a drug addict’s brain cells as speaking in gibberish, or unable to speak at all. Important messages aren’t being sent correctly, which contributes to the negative effects of addiction.

In a TMS procedure, researchers place a figure-8-shaped magnetic coil on the patient’s head. When turned on, the coil can send electrical signals into the brain. Importantly, brain cells communicate using electricity, and the “messages” between cells depend on the strength and frequency of these signals. Researchers found that the electrical signals from TMS help change the way brain cells “speak” to each other, getting rid of the gibberish and making cells communicate normally.

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TMS uses a magnetic coil to send electric signals into the brain.

In the case of drug addicts, the electrical signals from the magnetic coil are focused at a brain region called the dorsolateral prefrontal cortex (dlPFC). This is a part of the brain that handles decision making and cognitive ability, and is affected by drugs of abuse. For instance, drug addicts demonstrate lower dlPFC activity compared to non-addicted individuals during cognitive tasks.

Knowing how important this brain region is, researchers performed a study where they stimulated the dlPFC of drug addicts using TMS. They had cocaine addicts undergo either the TMS procedure or take medication (as a control group). They found that the cocaine users who experienced TMS had less cocaine cravings than their control counterparts. Further, the TMS group had more cocaine-free urine samples compared to the control group.

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The dorsolateral prefrontal cortex is affected by drug addiction.

Other studies support these results, focusing specifically on the prefrontal cortex, which appears to be a “sweet spot” for treating drug addiction. For instance, an earlier study found that daily TMS sessions, focused more broadly at the left prefrontal cortex, reduced cocaine craving. A later study honing in on the left dlPFC found similar reduction of craving in cocaine users.

Interestingly, the Italian TMS study was based on a rodent experiment with a very similar design. In this study, researchers allowed rats to develop a cocaine addiction and then stimulated a brain region analogous to the human dlPFC. Amazingly, the rats decreased cocaine seeking behaviors, much like their human counterparts in the TMS study. When this brain region was inhibited, or “turned off”, the rats increased their cocaine seeking.

Despite their promise, these TMS studies are just the beginning. Researchers are still a long way from developing a cure or reliable treatment for drug addiction. Like any new drug or treatment, it will be many years before TMS could be accepted as standard care for drug addicts. However, TMS has been successfully used to help patients in other ways. For instance, it has been used to help treat depression and is often used to help doctors identify damage from strokes, brain injuries, and neurodegenerative diseases. TMS holds a lot of promise and is on the cusp of being a successful drug addiction treatment. It’s only a matter of time before this stimulating idea becomes reality.

Peer edited by Robert Lee and Julia DiFiore.

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