Initially, THC boosted brain metabolism and synaptic protein levels, indicative of heightened cognitive processes. Subsequently, it shifted towards reducing metabolic activities in the body akin to the effects seen with caloric restriction or intensive exercise, known for their anti-aging benefits.
Maybe I’m misreading the only plot that mentions dosing numbers anywhere. It looks like the largest dosing group is getting 3mg/kg/day. That’s a lot scaled up to a 100kg person (like 10x a normal gummy for example).
It was three different doses, 0.3, 1, and 3 mg/kg per day
It was also delivered via subcutaneous pump, which is usually done with a mind towards a gradual dosing rather than a single push of the total amount all at once.
The kind of pump listed in the article previously linked was an osmotic pump.
Here’s an excerpt from a different paper describing the various methods for substance delivery:
Osmotic pumps are internally implanted devices that use an osmotic displacement system to infuse a preloaded substance into an animal. Use of these pumps permits constant dosing without the need to handle an animal after the initial implant surgery. Extracellular fluid is absorbed at a constant rate by an osmotic salt layer immediately beneath the permeable outer membrane. As the osmotic layer absorbs fluid, it swells and puts pressure on an impermeable reservoir in the center of the pump. The reservoir then expels the loaded substance from the pump at a constant rate through a flow moderator. The outflow can pass directly into the tissue surrounding the pump, or a cannula can be attached to the pump to direct the flow into a blood vessel or specific tissue.
Osmotic pumps are cylindrical in shape and come in sizes small enough for mice. These devices are surgically implanted either subcutaneously or intraperitoneally. The flow rate is fixed, and the duration of action varies from 3 d to 6 wk, depending on the size of the pump and the delivery rate selected. Pumps cannot be refilled but can be implanted sequentially to prolong dosing.
I’m not up on the dosing levels in humans, So I I don’t have the ability to know offhand if 3mg/kg spread over the day is unusually high (pun partially intended) or not. There’s a section I can’t find easily (I’m actually dyslexic so it takes me a while to get through this kind of dense and complicated writing) where they mentioned having a higher dose as a point of comparison.
Thanks this is a lot of great detail on the dosing mechanism that I think is really interesting. I love reading up on the experimental details and the actually components used to make these experiments work.
300mg of orally ingested THC spread out over 24 hours is about equivalent to consuming 1 typical candy/gummy every hour for 24 hours of the day. A reasonable or average or normal person would be uncomfortably high at these dosages. I also imagine the bioavailability of oral ingestion is less than the dosing mechanism you described although I’m not sure (is that getting taken up through the lymphatic system? How does it differ from oral ingestion or injection into the bloodstream?).
Fascinating stuff, thanks for sharing your knowledge.
Osmotic pumps tend to be equivalent to a transdermal patch in how the substance spreads through the body, but bypasses the need to go through skin. So, faster initially, but otherwise the dose over time would be the same, assuming the transdermal patch was able to maintain dosage (they aren’t, there’s a drop-off).
And, just as you said, the entire dose is taken in without any degradation by digestion, or being bound in something.
What I have zero clue about is what difference it would make in terms of numbers. It is equivalent in speed of uptake to subQ or IM injection, which is essentially immediate, just with a slight curve at the very beginning, so tiny it won’t be noticeable to someone that experienced all those deliveries.
Vs IV, the initial release is slower with osmotic pumps, but the sustain of the pumps makes everything after that different.
Basically, the pump goes under the skin and leaks the substance into the intracellular fluids, to be taken up by capillaries into the bloodstream.