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Greenlighter
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- Nov 16, 2016
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Chapter 2: Rates and Tolerance
I recently received a lot of heat over my thread titled "An introduction to rates and potency" due to a widespread and common misunderstanding on drug pharmokinetics/pharmacology that is the motivation for this series of posts. The theme of these is that it really does all come down to rates my fellow chemists, hobbyists and psychonauts. Don't take my word for it, but I am qualified to make these statements with my work experience and education.
Tolerance:
Everyone who's been in the game long enough has experienced it. It loathes both in its capacity to make you an immovable mass of misery and its potentiation to perform otherwise immoral acts by personal standards (stealing, cheating, 'dirty' things to get high---I've been there too). I want to help you understand what tolerance really is and why the conventional wisdom is sometimes accurate and other times not so relateable to the situation you may be in currently.
Tolerance occurs when a substance is repeatedly administered into the body that has a net effect of raising certain levels of neurotransmitters, hormones, or physiological responses (through stimulation of nerve pathways) for a duration long enough that a necessary but sufficient threshold is met.
I argue that the threshold is represented by the rate of excretion of the susbtance from the body plus interindividual variation due to different biological factors inherent in human diversity. Once a high enough concentration has accumulated of an active compound or its biproducts in your bloodstream, you have effectively reached the point where the conventional 'half-life' measurement of "how long will I be high for" comes into reality.
Let this chapter's example be the age-old, "How long until I can pass my drug test?" for marijuana/weed/hash/oil/whatever (I assure you they'll all get you properly stoned). It is TRUE that a one time smoker can smoke and pass a drug test beginning at T + 24-48 hrs because the threshold for failing is high enough that the one time user can excrete enough of the byproducts of THC in 1-2 half lifes to be below the requirement. This is because they had no lingering THC from past use (or buildup). The everyday smoker faces a much more difficult task as he/she must prepare well in advance (in the area of 3-7+ half life durations) to allow the body to excrete enough of the substance to be below the threshold.
Why? Because the body is capped at a certain rate of excretion that may or may not be dependent on the individual and may or may not be influenced by drinking water and other folk remedies. *Any manipulative techniques around the natural rate of excretion will still converge to a maximum rate*, which may or may not be enough to allow the user to pass by the time of testing.
When buildup like this occurs, the body can no longer eliminate a sufficient amount of the toxins produced by the substance in just a few or even 1 half life. The result is that you are stuck in a state characterized by elevated levels of residual byproducts in the bloodstream (or the active compound itself) for hours, days, weeks, or even months longer than you originally planned.
Until the satisfactory amount of time has passed to allow for the body to remove the substance, any subsequent high will be characterized by generally lower reported satisfaction with the drug. This is what we refer to as tolerance. Because you have now created a shift in your personal baseline concentration of the drug, and the rate of absroption by the body is capped at some natural limit, you will not be able to achieve as great of a spike (change in concentration, rush, many synonyms) as you were before.
Know your rates!
I recently received a lot of heat over my thread titled "An introduction to rates and potency" due to a widespread and common misunderstanding on drug pharmokinetics/pharmacology that is the motivation for this series of posts. The theme of these is that it really does all come down to rates my fellow chemists, hobbyists and psychonauts. Don't take my word for it, but I am qualified to make these statements with my work experience and education.
Tolerance:
Everyone who's been in the game long enough has experienced it. It loathes both in its capacity to make you an immovable mass of misery and its potentiation to perform otherwise immoral acts by personal standards (stealing, cheating, 'dirty' things to get high---I've been there too). I want to help you understand what tolerance really is and why the conventional wisdom is sometimes accurate and other times not so relateable to the situation you may be in currently.
Tolerance occurs when a substance is repeatedly administered into the body that has a net effect of raising certain levels of neurotransmitters, hormones, or physiological responses (through stimulation of nerve pathways) for a duration long enough that a necessary but sufficient threshold is met.
I argue that the threshold is represented by the rate of excretion of the susbtance from the body plus interindividual variation due to different biological factors inherent in human diversity. Once a high enough concentration has accumulated of an active compound or its biproducts in your bloodstream, you have effectively reached the point where the conventional 'half-life' measurement of "how long will I be high for" comes into reality.
Let this chapter's example be the age-old, "How long until I can pass my drug test?" for marijuana/weed/hash/oil/whatever (I assure you they'll all get you properly stoned). It is TRUE that a one time smoker can smoke and pass a drug test beginning at T + 24-48 hrs because the threshold for failing is high enough that the one time user can excrete enough of the byproducts of THC in 1-2 half lifes to be below the requirement. This is because they had no lingering THC from past use (or buildup). The everyday smoker faces a much more difficult task as he/she must prepare well in advance (in the area of 3-7+ half life durations) to allow the body to excrete enough of the substance to be below the threshold.
Why? Because the body is capped at a certain rate of excretion that may or may not be dependent on the individual and may or may not be influenced by drinking water and other folk remedies. *Any manipulative techniques around the natural rate of excretion will still converge to a maximum rate*, which may or may not be enough to allow the user to pass by the time of testing.
When buildup like this occurs, the body can no longer eliminate a sufficient amount of the toxins produced by the substance in just a few or even 1 half life. The result is that you are stuck in a state characterized by elevated levels of residual byproducts in the bloodstream (or the active compound itself) for hours, days, weeks, or even months longer than you originally planned.
Until the satisfactory amount of time has passed to allow for the body to remove the substance, any subsequent high will be characterized by generally lower reported satisfaction with the drug. This is what we refer to as tolerance. Because you have now created a shift in your personal baseline concentration of the drug, and the rate of absroption by the body is capped at some natural limit, you will not be able to achieve as great of a spike (change in concentration, rush, many synonyms) as you were before.
Know your rates!
