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Halflife 38 hours; How long after last dose is drug no longer considered "active"?

Marauder

Marauder

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Halflife 38 hours; How long after last dose is drug no longer considered "active"?

Taking the metabolites and their halflife out of the equation, approximately how long after my last dose of a drug that has a biological elimination half-life of 38 hours will this drug no longer be considered clinically active?

I may be asking the wrong question. The drug is an SSRI and by "no longer considered active" I mean when will this SSRI no longer bind to the serotonin transporter in such a way as to impact the SERT subjective effects of certain other drugs (MDAI, MDMA, etc.)

In practice this seems to be much more complicated. After being on an SSRI for a number of years, stopping for a few months after finishing withdrawal symptoms of said SSRI did not bring back any of the subjective effects associated with serotonin with MDMA, MDAI and methylone. MDMA and methylone felt like straight non interesting stimulants meaning I felt some dopa/norad effects but no serotonin effects. MDAI, not surprisingly, had no effects.

If anyone has experience or knows what the SSRIs may be doing to the brain of a rat after years of continued use, please chime in, even if only with a hunch. Danke.
 
The rule of thumb for elimination of drugs from the human body is, 7 half lives will bring the drug to less than 1% concentration.

If it's citalopram you're talking about .. which has a half life of about 38 hours... then the math says you should wait 11 days. This is usually "rounded up" to 2 weeks (14 days) and that's why you see the typical advice to discontinue SSRIs for 2 weeks before MDxx administration.

However, this math is only relevant for elimination of a single dose. If you've been on chronic SSRI therapy (e.g. taking them daily as prescribed for a while) you will probably need a much longer washout period of, I dunno, 2 or 3 months? Due to accumulation of the drug in fat deposits and the like.

Pretty much your only option is being patient. Attempts to force the SSRI out of your body are not going to do any good. Maybe try some serotonin agonists rather than releasers. (e.g. 2c-X versus MDxx).

Take your time, the drugs ain't going anywhere.
 
Half-life isn't the only factor here. Chronic SSRI use causes desensitization of 5-HT2A and other serotonin receptors, which will reduce the response to MDMA.
 
Some people say 5.5 half lives is the time it takes to "fully" clear a drug from the body. I'm not too sure why this is so because it correlates to approximately 2.2% of the original concentration remaining in the blood, which doesn't seem to be a very special number. As sekio said, with repeated dosing over time, the drug concentration in the blood will eventually reach a relatively stable concentration which would be much higher than the peak concentration achieved through a single dose, and as such you'd need to wait a much longer time. It'll also take some more time for receptors to sensitize as serotonin2A said, and I don't know if there is a predictable time frame of this happening. Your best bet is to wait a few months and try then.
 
The concept of half life seems to be quite complicated (don't understand why really, it's just like with the radioactive isotopes, or? But even many doctors and professionals think otherwise, that half life means how long a substance is effective and after 2x the value it will be excreted fully) ... but this explains why these fucking drug tests are so sensible for things consumed days ago sometimes.

If I think of memantine, which has a t 1/2 of 70-100h, now we take 85h x 5.5 = more than 19 days, and with chronic dosing this could even increase. Wow. Despite that, I always felt acute effects about 1 hour or so after ingestion and also a definite fading of effects after 2-3 days.
 
Yeah if you've been on those for a while you'll definitely need more than a few half-lives. Even if there's none of it in your body anymore, IIRC chronic SSRI administration does lead to a reduced SERT density which would mean a reduced serotonergic component to MDMA, much like one would get from rolling too often, of course without the psychological components of doing so...
 
dopamimetic said:
The concept of half life seems to be quite complicated (don't understand why really, it's just like with the radioactive isotopes, or? But even many doctors and professionals think otherwise, that half life means how long a substance is effective and after 2x the value it will be excreted fully) ... but this explains why these fucking drug tests are so sensible for things consumed days ago sometimes.

If I think of memantine, which has a t 1/2 of 70-100h, now we take 85h x 5.5 = more than 19 days, and with chronic dosing this could even increase. Wow. Despite that, I always felt acute effects about 1 hour or so after ingestion and also a definite fading of effects after 2-3 days.
Click to expand...

The basic concept of half-life is pretty much the same as for radioactive decay - the time it takes half of the drug to be excreted. Except human body is a little bit more complex than just that, so in reality drug excretion doesn't always follow exactly first-order kinetics. Besides, you have to also take changes in receptors et cetera into account. Do some doctors think that half-life means how long the drug is active? Well, that's just wrong by definition.

Now, 5 half-lives doesn't mean that you should feel the effects for that long. Again, changes in receptors and all kinds of things. I believe that with chronic use of substances with long half-lives you only really feel the effects for half a half-life or so.
 
Is this accurate (in terms of numbers, not subjective effects or taking into account metabolites, desensitization, etc.)

Code: 
# somefile.rb (sloppy Ruby code)
# 
dose = 20.0 # mg
halflife = 38 # hours
 
def timestamp(hours)
  days = hours / 24;
  if (days > 6)
    weeks = days / 7;
  end
  days = hours / 24;
  out = "#{days} days"  
  return weeks.nil? ? out : out + " (#{weeks} weeks)"
end

hours = 0
puts "dose #{dose} mg after #{hours} hrs " + timestamp(hours) #(#{hours / 24} days) " + weeks

considered_active = 0.01
while dose.to_f > considered_active do
  hours += halflife
  dose /= 2
  puts "dose #{dose} mg after #{hours} hrs " + timestamp(hours)
end

puts "dose #{dose} or 0.0 mg by cut off of #{considered_active} after #{hours} hrs " + timestamp(hours)


Sample output from dose 20.0mg & halflife 38hrs:

Code: 
#
#   dose 20.0 mg after 0 hrs 0 days
#   dose 10.0 mg after 38 hrs 1 days
#   dose 5.0 mg after 76 hrs 3 days
#   dose 2.5 mg after 114 hrs 4 days
#   dose 1.25 mg after 152 hrs 6 days
#   dose 0.625 mg after 190 hrs 7 days (1 weeks)
#   dose 0.3125 mg after 228 hrs 9 days (1 weeks)
#   dose 0.15625 mg after 266 hrs 11 days (1 weeks)
#   dose 0.078125 mg after 304 hrs 12 days (1 weeks)
#   dose 0.0390625 mg after 342 hrs 14 days (2 weeks)
#   dose 0.01953125 mg after 380 hrs 15 days (2 weeks)
#   dose 0.009765625 mg after 418 hrs 17 days (2 weeks)
#   dose 0.009765625 or 0.0 mg by cut off of 0.01 after 418 hrs 17 days (2 weeks)
#
 
Last edited:
Yeah that's correct. In fact you can approximate the blood concentrate of a single dose as follows: dose=initial dose*e^(-kt) where k=ln2/half life
 
Theoretically SSRI's should be producing long lasting changes in the number of serotonin receptors you have. Down regulation of the one's thought to cause depression play a major role in some of the drugs' you described effects. Its also possible that repeated binding to the serotonin transporters in your brain may have altered their structure and may need to be replaced by new ones. I know SERT is a G-Coupled protein receptor and not a voltage gated ion channel like the benzo receptor but its thought that the tolerance brought about by overuse or even regular use of benzos is due to the altering of binding site. Like someone else said, it might take a while, possibly years to feel the same effects. As sekio mentioned, you may want to see how some serotonin agonists work, as you might find less is more with them.

Also as a side not with drug half-lives you have to take into account bioavailability which ranges from person to person. Hell, some drugs they aren't even sure if they bioavailability is higher with food or not. As mentioned before it should be used as a rough estimate. Drugs like Prozac can/will stick around in you system for possibly months after a few doses.
 
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