SweetSue's Class Notes

[Tennessee Tim]

I too , went back to butter years ago at home. I do try to eat less animal fat and butter,because of calories, just as I try to reduce my sugar intake, for that reason And others. I increase my cannabis intake when I find myself worrying about food or anything else, too much!

 

[SweetSue]

Someday I intend to add that book to my library in a physical copy.

I pulled out Michael Backes’ Cannabis Pharmacy today, and was not surprised to find nothing on the treatment of COPD.

Uwe came through for me.

Reference

• SweetSue
• Apr 2, 2019

Just what I was looking for

• SweetSue
• Apr 2, 2019

 

[SweetSue]

Those are truly "class notes."

My wife reads the label on everything she buys...she's good to me like that .

You should see my notebooks. And that doesn’t cover the digital ones. Lol!

Wives are handy to have, aren’t they?

I too , went back to butter years ago at home. I do try to eat less animal fat and butter,because of calories, just as I try to reduce my sugar intake, for that reason And others. I increase my cannabis intake when I find myself worrying about food or anything else, too much!

The research I’ve been looking at suggests you’d do well to increase the consumption of butter from the milk of grass-fed cows Tim. The low-fat diet idea is a flawed construct with no scientific data to back it up. Trans fats are dangerous as hell. Healthy fats help the body maintain homeostasis.

 

[Tennessee Tim]

You should see my notebooks. And that doesn’t cover the digital ones. Lol!

Wives are handy to have, aren’t they?



The research I’ve been looking at suggests you’d do well to increase the consumption of butter from the milk of grass-fed cows Tim. The low-fat diet idea is a flawed construct with no scientific data to back it up. Trans fats are dangerous as hell. Healthy fats help the body maintain homeostasis.

You should see my notebooks. And that doesn’t cover the digital ones. Lol!

Wives are handy to have, aren’t they?



The research I’ve been looking at suggests you’d do well to increase the consumption of butter from the milk of grass-fed cows Tim. The low-fat diet idea is a flawed construct with no scientific data to back it up. Trans fats are dangerous as hell. Healthy fats help the body maintain homeostasis.

Agreed, Sue! I only limit fat to reduce caloric intake. My diet is rich in whole milk, butter, cheese, and animal flesh with fat! Much of my such intake is home produced or local if possible. Having been an organic gardener for decades (40 years) and raising my own chickens, turkeys, goats , sheep, pigs and cows, until a few years ago when I could not take care of it all anymore! I have been a holdover from another era as compared to my friends.

 

[SweetSue]

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.

A good start....

 

[SweetSue]

Chemical Structure and analysis of Phytocannabinoids


Chemistry and Analysis
of Phytocannabinoids
and Other Cannabis Constituents
Rudolf Brenneisen

 

[InTheShed]

Acid exposure degrades THC to CBN, which is only 10% as potent as Delta-9

Do they explain how they define "potent"?

 

[SweetSue]

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.

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)

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.

To be cont.....

 

[Tennessee Tim]

sesame oil? I wonder what other oils were tested? I have plenty of sesame oil! But have never used it with Cannabis!

 

[SweetSue]

sesame oil? I wonder what other oils were tested? I have plenty of sesame oil! But have never used it with Cannabis!

It may simply be that it’s a better medium-chain fatty acid. Over at Magnus’s topicals study hall they looked at a variety of oils and sesame wasn’t one they chose. I’d figure there was a good reason for that.

Cooking for edibles may present a different reason to choose sesame. When I get a moment I’ll look further and see if I can determine why they found cause to mention it here.

 

[SweetSue]

Smoking @beez0404 Hawaiian Mayan Gold this morning. Can’t type worth shit. It took four edits to get that last post right. Lol!

 

[SweetSue]

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.

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

• SweetSue
• Apr 3, 2019

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
​

cannabinoids in the bloodstream

• SweetSue
• Apr 3, 2019

(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.....

 

[SweetSue]

From The role of the endocannabinoid system in the brain-gut axis

In the ganglia that control visceral sensation, the gene encoding CB1 (CNR1) is regulated epigenetically under conditions of chronic stress— this finding might provide a mechanism that links stress with visceral pain.


The ECS is also involved centrally in the manifestation of stress, and endocannabinoid signaling reduces the activity of hypothalamic–pituitary–adrenal pathways via actions in specific brain regions—notably the prefrontal cortex, amygdala, and hypothalamus.

 

[SweetSue]

Reformatting so we can understand it easier.

16.2.1.4 Sublingual and dermal administration

Cannabis sativa plant extracts containing different cannabinoids with different effects are available or being developed as pharmacotherapies (see section 16.6).

These preparations are administered by the sublingual route to

* reduce toxicity associated with smoked cannabis, and
* to reduce first-pass metabolism.

Extract efficacy is being evaluated for analgesia, migraine relief, and spasticity among other indications.

Low (5.4 mg THC and 5.0 mg CBD) and high (16.2 mg THC and 15.0 mg CBD) oromucosal Sativex® (GW Pharma, Salisbury, England)

was compared to

5 and 15 mg synthetic oral THC in a

randomized, controlled, double-blind study in nine occasional cannabis smokers

(Karschner et al. 2011a, 2011b).

CBD, THC, 11-hydroxy-THC, and THCCOOH were quantified in plasma

by two-dimensional gas chromatography mass spectrometry (2D-GCMS).

There were significant differences (p <0.05) in the plasma THC Cmax and areas under the curve (AUC) from 0–10.5 h postdose for all analytes between low and high doses for both medications.

Read that again... “...significant differences... both medications.”

Similar absorption occurred with mean ± SE relative bioavailabilities of

92.6 ± 13.1% for 5 and 15 mg oral THC and

98.8 ± 11.0% for low- and high-dose Sativex®, respectively.

This study demonstrated similar bioavailabilities for Sativex® and oral THC.

In addition, there were no significant differences in THC effects with or without equivalent CBD

and no significant pharmacokinetic interactions between THC and CBD at the administered doses and 1:1 THC:CBD ratio.


”In addition, there were no significant differences in THC effects with or without equivalent CBD

and no significant pharmacokinetic interactions between THC and CBD at the administered doses and 1:1 THC:CBD ratios.”

 

[SweetSue]

16.2.2 Distribution

THC concentrations decrease rapidly after smoking due to
*distribution into tissues,
*hepatic metabolism, and
* urinary and fecal excretion.

THC is highly lipophilic and rapidly taken up by highly perfused tissues, such as lung, heart, brain, and liver.

It is estimated that 2–22 mg THC is necessary to produce pharmacological effects in humans (Huestis 2005).

I wonder if this estimation has since been revised somewhere. We now have evidence of pharmacological effects in humans with micro doses of 1mg.

Assuming 10–25% smoked THC bioavailability, 0.2–4.4 mg THC is the required smoked dose, with about 1% or 2–44 micrograms THC in brain at peak concentration.

Equilibration between blood and tissue THC occurred approximately 6 h after an i.v. THC dose.

When 200 micrograms/kg intrajugular THC was administered to pigs, blood terminal half-life was 10.6 h and volume of distribution (Vd) 32 L/kg, much larger than found in humans (Brunet et al. 2006).

The authors observed that the pig had a higher percentage of body fat which may contribute to the larger Vd but believed the model yielded valuable data to assist in interpretation of human cannabinoid results.

THC concentrations 0.5 h after 200 micrograms/kg intrajugular THC were
* blood 24,
*kidney 272,
*heart 178,
* lung 1888,
*muscle 55,
*spleen 34,
*fat 91,
*liver 155,
*brain 49,
*bile 0.4, and
*vitreous humor 1.2 micrograms/kg.

THC was eliminated fastest from liver and was unmeasureable after 6 h (<5 micrograms/kg).

THC concentrations decreased more slowly in brain than blood, but at 6 h were only 9% of those at 0.5 h.

Fat had the highest THC retention, with detection beyond 24 h. 11-OH- THC was only found in liver, and

THCCOOH was less than or equal to 5 micrograms/kg in most tissues.

 

[SweetSue]

16.2.2 Distribution

THC concentrations decrease rapidly after smoking due to
*distribution into tissues,
*hepatic metabolism, and
* urinary and fecal excretion.

THC is highly lipophilic and rapidly taken up by highly perfused tissues, such as lung, heart, brain, and liver.

It is estimated that 2–22 mg THC is necessary to produce pharmacological effects in humans (Huestis 2005).

I wonder if this estimation has since been revised somewhere. We now have evidence of pharmacological effects in humans with micro doses of 1mg.

Assuming 10–25% smoked THC bioavailability, 0.2–4.4 mg THC is the required smoked dose, with about 1% or 2–44 micrograms THC in brain at peak concentration.

Equilibration between blood and tissue THC occurred approximately 6 h after an i.v. THC dose.

When 200 micrograms/kg intrajugular THC was administered to pigs, blood terminal half-life was 10.6 h and volume of distribution (Vd) 32 L/kg, much larger than found in humans (Brunet et al. 2006).

The authors observed that the pig had a higher percentage of body fat which may contribute to the larger Vd but believed the model yielded valuable data to assist in interpretation of human cannabinoid results.

THC concentrations 0.5 h after 200 micrograms/kg intrajugular THC were
* blood 24,
*kidney 272,
*heart 178,
* lung 1888,
*muscle 55,
*spleen 34,
*fat 91,
*liver 155,
*brain 49,
*bile 0.4, and
*vitreous humor 1.2 micrograms/kg.

THC was eliminated fastest from liver and was unmeasureable after 6 h (<5 micrograms/kg).

THC concentrations decreased more slowly in brain than blood, but at 6 h were only 9% of those at 0.5 h.

Fat had the highest THC retention, with detection beyond 24 h. 11-OH- THC was only found in liver, and

THCCOOH was less than or equal to 5 micrograms/kg in most tissues.

The authors observed that the pig had a higher percentage of body fat which may contribute to the larger Vd but believed the model yielded valuable data to assist in interpretation of human cannabinoid results.

THC concentrations 0.5 h after 200 micrograms/kg intrajugular THC were
* blood 24,
*kidney 272,
*heart 178,
* lung 1888,
*muscle 55,
*spleen 34,
*fat 91,
*liver 155,
*brain 49,
*bile 0.4, and
*vitreous humor 1.2 micrograms/kg.

I realize this is pig data, not human, but isn’t it interesting how much more went to the lungs? Look how low blood levels were too. We keep hearing how low blood plasma levels are. Maybe it’s because the cannabinoids are being picked up all along the way.

 

[SweetSue]

I wanna know what really goes on when we administer cannabis in all its many forms. We’re still only guessing. There’s got to be more recent info. Time to get back to Prof of Pot.

 

[Tennessee Tim]

sounds like i have been dosing the wrong end! but like I been saying, the thc is active in treating pain,with or without cbd. The whole enchilada for me, but plenty of thc!

 

[SweetSue]

sounds like i have been dosing the wrong end! but like I been saying, the thc is active in treating pain,with or without cbd. The whole enchilada for me, but plenty of thc!

They treat pain in different ways, and they always work best together. THC makes you not care so much about the pain, it makes it a distant bother instead of in your face.

CBD gets busy doing something about getting rid of future pain by soothing inflammatory response.

Together, even in small ratios, they do so much more than on their own.

I find it interesting that both THCA and B-caryophyllene will do the same things CBD does but in different ways.

Geez.... I love learning this stuff.

 

[Tennessee Tim]

They treat pain in different ways, and they always work best together. THC makes you not care so much about the pain, it makes it a distant bother instead of in your face.

CBD gets busy doing something about getting rid of future pain by soothing inflammatory response.

Together, even in small ratios, they do so much more than on their own.

I find it interesting that both THCA and B-caryophyllene will do the same things CBD does but in different ways.

Geez.... I love learning this stuff.

They treat pain in different ways, and they always work best together. THC makes you not care so much about the pain, it makes it a distant bother instead of in your face.

CBD gets busy doing something about getting rid of future pain by soothing inflammatory response.

Together, even in small ratios, they do so much more than on their own.

I find it interesting that both THCA and B-caryophyllene will do the same things CBD does but in different ways.

Geez.... I love learning this stuff.

Ahh! The herbalist life for me!