Continuing on....
Handbook of Cannabis
Chapter 16 Cannabinoid Pharmacokinetics and Disposition In Alternative Matrices
- Marilyn A. Huestis and Michael L. Smith
Pharmacokinetics
- absorption following diverse administrative pathways
- distribution throughout the body
- metabolism by tissues and organs
- elimination in the feces, urine, sweat, OF, and hair
- how these processes change over time
Cannabis plants contain over 100 different cannabinoids, incl. THC
THC is the primary psychoactive component
- THC may degrade when exposed to air, heat, or light
- Acid exposure degrades THC to CBN, which is only 10% as potent as Delta-9.
This was the first time I caught the “may degrade” suggesting that it doesn’t in the way we’ve been trained by stoner science to accept.
- THC contains no nitrogen
what’s the significance of this?
- THC has two chiral centers in
trans-configuration
Chiral centers are tetrahedral atoms (usually carbons) that have four different substituents. Each chiral center in a molecule will be either R or S. As noted above, molecules with a single chiral center are chiral. Molecules with more than one chiral center are usually chiral. The exception are meso-compounds.
- described by the dibenzopyran or delta 9 system
| ChEBI Name | dibenzopyran | | | | ChEBI ID | CHEBI:39203 | | | | Definition | Any organic heteropolycyclic compound based on a skeleton consisting of a pyran ring fused with two benzene rings. |
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16.2.1.1 Smoking
In 2005 Huestes described important aspects of cannabis administration through smoking
- bioavailability rate is 25% with wide variability
- smoked THC is rapidly absorbed from lungs
- reaches peak plasma concentrations prior to end of smoking
- Cmax in about 6 - 10 min
- Peak plasma THC concentrations only slightly lower after smoking compared to after intravenous (i.v.) administration
A mystery: why would peak plasma concentrations of smoking match those of i.v. administration? This suggests to me that the current method of testing is missing something significant.
- smoking 16 mg THC doses respective mean +/- SD plasma THC concentrations were
7.0 +/- 8.1 and 18.1 +/- 12.0 micrograms/L
- following 1 inhalation with mean (range) Cmax of 84.3 (range 50-129) and 162.2 micrograms/L (76-267)
- after inhalation
- mean THC concentrations are 60% at 15 min
- mean THC concentrations are 20% at 60 minutes
- at 2 hours they fell to <5 micrograms/L
- smoking allows patient to self-titrate to suit their own lifestyles and needs
During cannabis smoking
- THC metabolizes to equipotent 11-hydroxy-THC (11-OH-THC)
- THC also metabolizes to inactive 11-not-9-carboxy-THC (THCCOOH)
16.2.1.2 Oral Administration
THC is readily absorbed due to its high octanol/water coefficient
- estimated at 6000 to 9 million
Absorption is slower when ingested, with lower, delayed peak plasma concentrations
Influences to absorption
- dose
- route of administration
- vehicle of administration
- rates of absorption, metabolism, excretion
Relevant info
- about 6% bioavailability
- using sesame oil as a carrier improves bioavailability
OK, why sesame oil?
- plasma Cmax is 2 - 6 hours
- you can have two peak THC concentrations after ingestion (enterohepatic recirculation)
- 5 hours after ingesting 20 mg dose peak plasma THC concentrations 4.4 - 11 micrograms/L
* similar concentrations register after 10 mg Marinol
Consider that. Marinol, synthetic THC that’s not fondly accepted by patients pretty across the board, takes half the dose. It also lacks the synergistic components you get with cannabis.
Cannabinoids in the bloodstream: oral administration
(Goodwin et al. 2006)
Subjects of double-blind test received dose of either
* 14.8 mg of THC in hemp oil
* 7.5 mg dronabinol
Plasma THC and 11-OH-THC
never exceeded 6.1 micrograms/L
Cannabinoids were always
<0.5 micrograms/L
15.5 hr after last dose
THCCOOH concentrations
exceeded 1.0 micrograms/L
* 1.5 hr after first dose of dranabinol
* 4.5 hr after first dose of hemp oil
THCCOOH peaked as high as 43 micrograms/L
39.5 hrs after last dose THCCOOH
was always 1.0 micrograms/L or less
Cannabinoid concentrations were similar
for 7.5 mg dronabinol and 14.8 mg of hemp oil
(Schwilke et al. 2009)
Chronic daily cannabis consumers in a closed research unit
- given 20 mg THC administered every 4-8 hours in escalating daily doses (40-120mg)
- 7 day stay
Mean +/- SE free plasma readings
After admission, no drugs administered yet
At 19.5 hrs:
THC: 4.3 +/- 1.1
11-OH-THC: 1.3 +/- 0.5
THCCOOH: 34.0 +/- 8.4
During dosing 11-OH-THC and THCCOOH rose, but THC didn’t.
22.5 hrs after last dose:
THC: 3.8 +/- 0.5
11-OH-THC: 3.0 +/- 0.7
THCCOOH: 196.9 +/- 39.9
Plasma concentrations remained > 1 microgram/L for at least 1 day after smoking
- also after cessation of oral doses
* The argument is often made that plasma THC >1 microgram/L is evidence of recent cannabis use.
This study proved that contention wrong over a decade ago.
16.2.1.3 Rectal administration
(Huestis 2005)
Highest bioavailability of suppositories tested was THC-hemisuccinate (13.5%)
I’d like to know what formulations they used. Later gator. 
They felt this formulation maximized bioavailability and reduced first-pass hepatic THC metabolism.
Oral doses of 10-15 mg of Marinol (to treat spasticity)
THC peaked after 1-8 hrs at
2.1 - 16.9 micrograms/L
Look at that variability! 
After 2-8 hrs rectal doses of 2.5-5 mg THC hemisuccinate produced
1.1 - 4.1 micrograms/L
Rectal bioavailability was approximately twice that of oral administration.
to be continued.....
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And that doesn’t cover the digital ones. Lol! 
It took four edits to get that last post right. Lol!
