• 4 Oct 2018 2:33 PM | C.


    Everyone loves benzodiazepines - they are like the chocolate bar in the prescription candy shop: a staple that almost everyone enjoys indulging in. I am no exception to that.  However, I have made a decision that the abuse potential of the benzodiazepines is too high for me, and that I must permanently restrict myself from them. 

    I was prescribed Xanax when I first went to college to help with social anxiety, panic attack disorder, and mild insomnia (which later got much, much worse). I made switches to both Ativan and Valium throughout my college career due to the quick build up of tolerance these drugs are prone to and the fact that I was using them extensively, to the point of excess. In short, they work incredibly well to eliminate the symptoms, but they don't eliminate the cause. In fact, they help to mask the cause by providing an escape from the symptoms.


    Class: Benzodiazepine
    Prescribed for: General Anxiety, Panic Attack disorder, Insomnia
    Mechanism: Allosteric GABA-A Modulator (benzodiazepine site)

    The "benzos" are an entire class of drugs that all share the common backbone structure above. A benzene ring is a flat, six-membered ring with resonating double bonds (shown above as a hexagon with a smaller circle inside, the smaller circle is to notate the double bonds). A diazepine ring is a seven-membered ring with two nitrogen atoms (shown above on the right side with two teal nitrogens). So a benzodiazepine is the combination of these functional groups.

    There are many different types of benzodiazepines that all have a similar function - the difference chemically has to do with the "R groups" (circled in red on the image). All of the benzodiazepines bind to the GABA-A receptors in the brain at the same spot as Ambient (Zolpidem)! It works in a similar manner - by increasing the effect of GABA in the brain. GABA is an inhibitory neurotransmitter, which means it decreases brain cell activity. When the benzodiazepines are on the GABA-A receptor and GABA binds, it is able to have a larger effect than it normally does.

    One of the most interesting facets of pharmacology is how two drugs can bind to the same place on the same receptor and cause very different effects. This is because proteins are very flexible, squishy molecules and when a drug binds to it, it changes the way this squishy molecule is shaped. This is called "induced fit." So two different molecules can bind to the same place, but change the shape slightly differently which leads to different therapeutic effects. Likewise, two different molecules can bind to different places, but change the shape the same and lead to the same effect! It's crazy.


    MY PERSONAL TAKE

    For many out there, the benzodiazepines are successful treatment for their anxiety-related problems. Where I differ from them is my innate vulnerability to substance abuse due to my neurodiversity and a lack of self-control when it comes to reducing or eliminating my self-awareness of my own emotional and physical pain. I am always anxious. For me, the anxiety is not the disorder that needs semi-regular intervention, it is always present. So it then becomes very, very difficult when presented with a prescribed drug that takes it away to monitor and control my usage. This is one of the reasons abortive medicines have such a strong addictive potential. I had a very negative experience where I semi-accidentally took too many benzodiazepines to try to end a panic attack that resulted in my then ex-girlfriend giving me an ultimatum about them. After we broke up, I considered resuming using them under stringent conditions, but have since come to the conclusion that it's not worth the risk of falling back into substance abuse. And as annoying as it is to accept that she was right about it, it's true.

    A random yet interesting fact about the benzodiazepines is that they will get rid of a "bad trip" when someone is activating their serotonin system with LSD. It is well known that benzodiazepines can eliminate the repetitive loop of a bad trip and allow the person to come out of that state. What's interesting about this to me is that it is a perfect matching of classical neuropharmacology. LSD activates the serotonin system, specifically the 5-HT2A Receptor, which is mainly excitatory. If someone takes too much LSD and is in a hyper-excited state, the benzodiazepine - which functions through GABA, an inhibitory molecule - corrects that effect. Most of the time with effects in the brain, it doesn't work like a simple addition problem, but in this one case it seems like it does!

  • 1 Oct 2018 2:37 PM | C.

    Cannabis is often referred to as a drug in a singular manner, but in reality there are hundreds of compounds in whole-plant derived Cannabis medications that can lead to different therapeutic effects (the way these different molecules interact for form specific effects is called the Entourage effect and will be covered in detail later).

    The medicinal properties of the Cannabis plant come from these chemicals that the plant produces: mainly cannabinoids and terpenoids. Since these chemicals are not involved in the primary processes of the plant (growth, development, or reproduction), they are called secondary metabolites. Some commonly-known secondary metabolites are menthol (found in mint) and capsaicin (found in chili peppers, make them spicy!).

    But there are also some drugs that were derived from secondary metabolites, as well. Aspirin's predecessor (salicylic acid) is a secondary metabolite from the willow plant. Likewise morphine is a secondary metabolite from the poppy plant!

    The two drugs in Cannabis that have been researched the most are D9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Back in the 1960's THC was purified and identified as the psychoactive component of Cannabis and was later used to identify the specific drug target that it interacts with in humans - the Endocannabinoid System (ECS). 

    Specifically, THC was found to interact with the Cannabinoid 1 (CB1) Receptor. But since then, there has been a lot of research surrounding the entire ECS. Before we go on to cover the system as whole, we'll take a step back and look at exactly what a receptor is and how it works in our bodies.

    For now, please ask any questions pertaining to THC and CBD as secondary metabolites! We will be covering their individual profiles separately after diving through the ECS basics!

  • 25 Sep 2018 2:19 PM | C.

    A drug is any chemical we take for a specific therapeutic action. But just how exactly do these chemicals cause these actions? Generally speaking, each drug has one target within the human body that it interacts with - this interaction between the drug and its target is what causes the therapeutic effects. So what are the things the drugs are working with? For over 90% of drugs, their targets are proteins within the body.

    When the word protein comes up, most people think of it in the context of nutrition. In nutrition, protein is a class of nutrients the body needs to intake in order to build muscle, maintain the immune system, and function properly. When you are eating nutritional protein, what you are eating on an atomic scale is millions and millions of individual protein molecules (a molecule is anything that is made up of more than one atom like water or a drug). These protein molecules perform chemical reactions that allow our bodies to execute actions. For example, networks of proteins are responsible for sight, hearing, digestion, and all thoughts.  When you snap your fingers, millions of proteins perform synchronized chemical reactions to allow you to do this! In fact, any time you do anything your body's proteins are busy at work. These proteins are all very different from each other; each one is designed with a specific "job" to do. Drugs interact with the proteins and preventing or changing how the proteins do their "job" is how drugs work

    Now there are two main types of protein molecules that drugs target called receptors and enzymes. 

    Receptors are proteins that can be turned on or off by a drug. You've probably heard of the serotonin receptors or dopamine receptors in the brain - these are receptors that are turned on by serotonin or dopamine, respectively. When a drug interacts with a receptor, it can turn it on or off. The receptor then tells the rest of the cell what to do. An example of a drug that targets a receptor is morphine. Morphine turns on the opioid receptor which then leads to decreased pain.

    Enzymes are proteins that perform chemical reactions. They usually are involved in either making something or breaking it apart. A drug typically will turn off an enzyme and prevent it from making its product. An example of a drug that targets an enzyme is Advil. Advil (ibuprofen) turns off the enzyme called COX (cyclo-oxegenase) which leads to reduced inflammation and reduced pain. 

    My entire dissertation was on one enzyme specifically in the endocannabinoid system. I'll be posting a lot about the specific drug targets that have been evaluated in the ECS later!

    That's it for now - if you have any questions related to drug targets, feel free to ask!

  • 22 Sep 2018 11:30 AM | C.

    Hello there! 

    I'm going to try something different in terms of the stereotypical educational blog. I'm going to post very short, brief, interchangeable sections in larger chapters here each month. They will build upon each other, but only slightly. Readers will be able to either read the information in the order I believe most useful, or skip around to what they find most interesting.

    I'm a pharmacologist - someone who has studied the interaction of drugs with the human body. Specifically, I studied drug discovery in the endocannabinoid system. Pharmacology is the study of drugs and I believe that understanding drug mechanisms and interactions is a critical piece of knowledge that is often undervalued in society.

    Over this next month I will be covering topics on this blog pertaining to the very bare-bones basics of Cannabis pharmacology. This initial chapter will serve as the absolute foundation for all the further material I will be covering. 

    Here are the sections to be covered:

    Section 1: How does a drug work? What is a drug target?

    Section 2: What drug(s) are in Cannabis? What is a secondary metabolite?

    Section 3: What is a receptor? What type of receptors are CB1 and CB2?

    Section 4: What does THC do to the CB1 and CB2 receptors? What does CBD do?

    Section 5: What do the CB1 and CB2 receptors do in the body in the absence of Cannabis?

    Section 6: What makes up the endocannabinoid system? Where is it in the human body?

    Section 7: What do we know about the endocannabinoid system so far?

    Section 8: Comprehensive review of covered concepts

    Next up is Chapter 2 which will focus on pharmacokinetics, dosing, and toxicity.

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