UPDATED: 10 May 2024
I wrote this so that we can understand the metabolic process better and the role that genetics plays, which then hopefully should lead to an increased awareness of the potential **harm** and benefits associated with **optimising the psychoactive effects** of the substances we enjoy.
* **It's all genetics, right ?**
Yes, it's obviously all down to our **genes**, which are the **"blueprints"** of the many and the various components they form or **express**, and this **degree of variation** is as **different** as our **individual** features and behaviours.
And that's because of **protein**, which is found throughout the body—in muscle, bone, skin, hair, and **virtually every** other body **part or tissue**. It makes up the **enzymes** that power the many **chemical reactions** and the **hemoglobin** that carries **oxygen** in the **blood**.
The **synthesis of a protein** is governed by the **information** in its **DNA**, which is **polymer** or a **long chain** of different sized molecules, and is not a protein nor a lipid nor a carbohydrate (which I *assume* is probably to keep it distinct from the catabolic process), with the help of messengers (**mRNA**) and translators (**tRNA**).
* **Why isn't absorption part of metabolism and why is it part of "tweaker's" lore ?**
Absorption **starts before** and is **independent** from/of metabolism, yet the two **influence eachother**, as anyone who's taken drugs on an empty stomach can attest.
Most drugs get metabolised in the **liver** and that means that they need to **get into the blood first**, and that happens by **absorption**, and the **degree** that it happens is measured by it's BA or **bioavailability**.
It's **degree** (mentioned above) is influenced by **what** and **when** you've **eaten** as that affects the **pH** or the **p**otential or measure of the concentration of **H**ydrogen ions of the stomach's natural digestive **hydro**chloric **acid** and this is some of the **lore** that "tweakers" share.
That being, a **basic** substance like **baking soda** or an **antacid** can significantly boost absorption of their **weak base stimulants** because a strong base can raise their **pH**, and that **increases** the **amount** of it's **lipid soluble molecules** mainly through the lipid-soluble **membranes found in the brain**.
In the case of amphetamine, the time it takes to be fully absorbed is as long as it feels 👍.
**IVDUs** 💉or Intravenous Drug Users are also preoccupied by not only the **💯% BA**, but by the **rush**, as the **absorption process is bypassed altogether** as the drug becomes **available** almost **immediately**.
This is considered to be another, often **highly risky** and more **extreme** form of addiction, but some drugs like Morphine, Dilaudid and Heroin have such a **low oral or snorted BA**, they encourage injection because it seems like a more practical and economical ROA or Route of Administration.
Then after being metabolised, they are then **eliminated** by the various organs, such as the kidneys, skin or bowels.
* **What is involved in the metabolic process ?**
Firstly, in your mind, you need to logically **separate** them into both **food and drugs**, despite being inextricably linked.
Secondly, you need to recognise that we all **metabolise at different rates** or speeds and to different **degrees**.
A few drugs **do not get metabolised**, like Lyrica and Gabapentin, because they are **not protein bound** and *maybe* because they work with the positively charged ionic (bioelectrical) molecules of **Calcium** (Ca+), which every nerve cell needs to communicate, but **is not synthesised in the body**.
**Drugs** get mainly metabolised in the **liver** whereas **foods** do so mainly in the **stomach and small intestines**.
The metabolic process is critical for these main reasons:
1. If what we ingest is a **nutrient** that has stored **energy**, like **food**, then we can use that energy (like from carbohydrates, fats and sugars) immediately by "burning it" as we **catabolise or break it down** by our **digestive acid and enzymes** to split up the proteins into amino acids and **glucose**, for example, otherwise we won't have enough fuel or **energy** that our organs and muscles need to keep us moving.
2. As well as doing the same with the nutrient's various groups, such as the **macro**nutrient carbohydrate and protein (complex amino acids) for example, and **convert them** into smaller and simple components, such as amino acids, for example, to keep us functioning in ways that are not so physical, such as thinking, learning, emoting etc.
3. We need to **anabolise rebuild or replete** our biochemical supplies either by using them directly or by **converting** the various and simple components into more **complex** ones such as our **DNA, proteins** (to build **muscle and neurotransmitters**, for example) and **lipids**, by **synthesising** them in all the different cells distributed all over our brain and body, and then **storing** what is left over into our fat cells.
* **How can we get more stoned and please explain the risks ?**
If we **don't metabolise the drug fast enough** then it will **stay** in our blood stream for **longer**, exert it's **effects** for **longer** and even **keep building up**, especially if it hasn't **finished being absorbed**.
This is when we feel **potentiation**, which is mostly good value for us, for obvious reasons like saving drugs and/or 💰, **however** it increase our **tolerance** and then be considered to be an **overdose**, which can easily become so ⚠️ **toxic**, that it can become **lethal** and kill us ☠️.
However, if the drug is **inert** or **not psychoactive** or **not a co-drug, pro-drug or a precursor** then we probably will be very disappointed 😞, and then we need to change our supplier or complain to the dealer.
The **anabolic** process, after **at least one** metabolic **pass** through mainly the **liver**, is processed by at least one or many of the **genetically expressed** group of **enzymes**, which are proteins or **biological catalysts** that speed up the process, of the **cytochrome** (water soluble protein) that is **encoded** by the **P450 genes**.
Many drugs and foods can **inhibit the function** of those CYP or **CY**tochrome **P**450 **enzymes** during metabolism, such as **grapefruit**, causing the phenomenon described in the opening paragraph, and is explored in great depth at
https://www.reddit.com/r/Drugs/s/1W6HifcUYd * **What are prodrugs and codrugs and why are they popular ?**
A **prodrug** is inactive and often **considered to be less abusable** due to it's longer onset and duration time and it's **route of absorption limitations**, than it's metabolites, and which **needs to be metabolised** into it's psychoactive metabolite(s), **before it exerts it's effects**.
A **codrug** or "mutual prodrug" consists of two synergistic drugs chemically linked together to a single molecule, in order to improve the drug delivery properties of one or both drugs, such as Captagon or Fenethylline, the drug that fuelled ISIS and the Middle East.
Prodrugs, like Codeine, LDX or Lisdexamphetamine (Vyvanse) or GBL, convert into, in the case of LDX, to both a 👍 psycho**active** and into a (psycho-?) **inactive** compound 🙁, such as lysine.
Prodrug metabolism can be unpredictable and complex such as **1,4 Butenediol** or "BDO", which requires a much-slower-than-it's metabolite's **two passes** through the liver, for example, from the inactive BDO > GBL > **active** GHB, yet crosses the BBB or Blood Brain Barrier faster than it's metabolites.
Yet, one of it's metabolites, GBL is **metabolised faster than it's metabolite**, GHB. When the neuro-inhibitor, **alcohol is combined** with it and/or any of it's metabolites, then **counter-intuitive outcomes** can be observed.
⚠️ The yield depends on how much of an **extensive metaboliser** you are, and in the case of Codeine, a higher than expected average yield of 4% of Morphine, can be dangerous and even lethal.
Take [this link](
https://www.reddit.com/r/Drugs/s/Hve306TfyW) should you wish to explore drug metabolism.
**References**
* Amphetamine: Uses, Interactions, Mechanism of Action - DrugBank
https://go.drugbank.com/drugs/DB00182 * Interaction between γ-Hydroxybutyric Acid and Ethanol: A Review from Toxicokinetic and Toxicodynamic Perspectives
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965651/
May 28, 2019, 07:15:12 AM
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