Thanks everyone, I appreciate the replies, but you may have gotten the wrong idea—I’m not short on personal experience (which is actually part of why I’m asking, but that’s a different story). For this question, I am specifically interested in smoked THC (well, ultimately I mean smoked cannabis—I refer to THC mainly for convenience’s sake, as it’s really the cannabinoid with the most research done into it). Anyways, I’m really wanting to get at the nitty-gritty of cannabinoid pharmacology/pharmcokinects—ultimately, whatever the interaction between the two may be in creating the
duration of an average high (I know that’s oddly specific, call it a pet project). I guess after recently reading that THC’s terminal half-life will (conservatively) vary anywhere from 25-35 hours, I was a bit thrown off. Basically, from what I think I’ve grown to understand, this is a result of its high liposolubility—the body absorbing most of it into fats and eliminating very slowly from there over time—and thus is no indicator of actual THC clearance rates in plasma.
I’ve looked into things a bit more and this seems to be the most worthwhile bit I’ve found so far:
http://drugstestingbook.com/cannabinoids/cannabinoid-pharmacokinetics/
The article is good and thorough, but there’s a lot of extraneous info—its primary focus is around drug tests and the like—which is not at all what I’m interested in. Key point, I wouldn’t recommend reading all/much of it, but to any others who are interesting, there’s some nice things to be gleaned. Anyways, here’s where it gets even more confusing:
The disposition of THC acid its metabolites after smoking a single placebo, 1.75% or 3.55% THC cigarette was followed in plasma over 7 days. THC was detected in the plasma immediately after the first cigarette puff (Figure 13-1). Mean ± SD THC concentrations of 7.0 ± 8.1 µg/L and 18.1 ± 12.0 µg/l were observed following the first inhalation of a low- (approximately 16 mg) or high- (Approximately 30 mg) dose cigarette, respectively. Concentrations increased rapidly, reaching mean peaks of 84.3 µg/L (range 50-129) and 162.2 mg/L (range 76-267) for the low- and high-dose cigarette, respectively. Peak concentrations occurred at 9.0 min, before initiation of the last puff sequence at 9.8 min.
Despite a computer-paced smoking procedure that controlled the number of puffs, length of inhalation, hold time, and time between puffs, there were large inter-subject differences in plasma THC concentrations because of differences in the depth of inhalation as participants titrated their THC dose (Figure 13-2). Mean THC concentrations were approximately 60% and 20% of peak concentrations 15 and 30 min post-smoking, respectively. Within 2 h, plasma THC concentrations were at or below 5µg/L. The time of detection of THC (GC/MS limit of quantification [LOQ] = 0.5 ug/L) varied from 3 to 12 h after the low-dose and from 6 to 27 h after the high-dose cannabis cigarette.
The quote is from the top of the page, along with a nice little chart. The chart basically shows a
massive drop off in plasma THC concentrations during only 10 or so minutes after smoking.
I’m not sure what this is meant to imply; some of it is metabolized to the also active 11-OH-THC (which is supposed to be roughly equipotent in theory?). From there, it doesn’t provide much insight into how long that’s staying in the system.
My pharmacology and such is all a bit rusty, but I was always of the impression that plasma levels of a given substance tend to more or less correlate directly with the levels of that given substance in the brain, synapse, etc (factoring in whatever blood/brain barrier issues may be at play—the main point being, serum levels go down=levels in the brain going down); is this untrue/oversimplified?
So clearly, a huge portion of the THC is rapidly absorbed into lipid-y tissues and such—but then, is this meant to imply that THC being slowly released from the body fat stores in general is in some way responsible for the effects after smoking? Or is there something to do with THC stored in actual fatty substances in the brain, and seeping out directly there? Further, not a ton of insight is given into 11-OH-THC pharmacokinetics—whether or not it’s absorbed/metabolized at a similar rate as THC itself, and thus, how much this is effecting things.
To be honest, I’m a bit lost.
Is there just something I’ve missed or misread here?
Right now the main facts I think I'm dealing with:
a. THC’s terminal half-life in the body is in the range of dozens of hours
b. despite the numinous other—active and inactive—cannabinoids in pot, THC itself is typically referenced as being the primary agent responsible for effects (whether this be from it’s metabolites (11-OH-THC) I haven’t found a clear answer, but it the effects of the metabolites (or at least what we know of them for sure) always seem downplayed. Clearly, at least THC on it’s own—while clearly not the only culprit—must at least do a fair amount of something (hence Marinol existing (as shitty as it might supposed to be)))
c. THC seems to rapidly leave the bloodstream after smoking, doing so at a rate that seems far too quick to line up with the typical cannabis-effects duration (2ish, maybe 3 hours for most people, but seriously, for some, this can be a lot longer…)
Sorry for the long post—I know this is all kind of vague/complicated, and I might be missing something really stupid. If there’s anything I’m seeing wrong, please, let me know (as you can see I haven’t posted before and so might be susceptible to error
).
Any light that could be shed on any of these questions would be a tremendous help.
Thanks everyone
