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macckone
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[*] posted on 11-10-2021 at 08:36
CBD as a chemotherapy agent (split from CBD solubility in organic solvents)


https://www.nwsci.com/customer/docs/SKUDocs/RMR/Technical%20...

Pure cbd is used as a chemo agent with all of the usual problems associated with chemotherapy, nausea, vomiting, potential liver damage, etc. Canabinoids at high concentrations over an extended period of time even have their own specific illness:

https://www.cedars-sinai.org/health-library/diseases-and-con...

THC and CBD are relatively benign drugs but they are still drugs and can have side effects.
They still have a much better theraputic margin than many common drugs like ibuprofen and acetominophen (paracetamol)
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[*] posted on 11-10-2021 at 09:04


Quote: Originally posted by macckone  

Pure cbd is used as a chemo agent with all of the usual problems associated with chemotherapy, nausea, vomiting, potential liver damage, etc.

can you evince that?
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[*] posted on 12-10-2021 at 04:19


Quote: Originally posted by macckone  

Pure cbd is used as a chemo agent with all of the usual problems associated with chemotherapy


Really…

Quote: Originally posted by macckone  

THC and CBD are relatively benign drugs but they are still drugs and can have side effects.
They still have a much better theraputic margin than many common drugs like ibuprofen and acetominophen (paracetamol)


…as is quite typical for chemotherapeutic agents /s
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[*] posted on 12-10-2021 at 07:14


One link, there is a ton of information about CBD for chemotherapy but it is still in trials.
https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabi...

CBD has not been approved but at high doses it kills rapidly dividing cells, which is what chemo agents do. It causes nausea and vomiting as well as cell death in the intestinal lining. The trials are really promising for colon cancer which is of particular interest to me as colon cancer survivor. It is one of the most promising new chemotherapy agents for colon cancer out there.

The new phenomenon of the canabanoid syndrome seems to be somewhat akin to withdrawal.
Ie, long term high dose use does cause a change in the gut. But unless you are smoking the really strong stuff close to 24/7 you are unlikely to get it. I provided a link in the previous post.

stoichometric_steve, do not confuse smoking pot with drug level doses used for chemotherapy. CBD has other uses, ie epilepsy, where the safety margin is really good. THC is an anti-nausea medication for chemo. I still have some in the refrigerator, but at high doses it can literally have the opposite effect. You start mucking about with nerve receptors and weird shit happens. You are unlikely to OD on pot, but when you start taking edibles and actual time release medication it gets trickier.

The safety margin of paracetamol is one of the lowest of any drug on the market. And it is OTC. Take too much and you get severe liver damage. That is extremely well documented.
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[*] posted on 12-10-2021 at 09:20


You seem to be muddling two ideas of chemotherapy.
Yes CBD is used (experimentally) in the treatment of cancer and it's a chemical (rather then surgery or radiotherapy) so that makes it chemotherapy.

But it's not the same sort of chemical that causes "all of the usual problems associated with chemotherapy, nausea, vomiting, potential liver damage, etc." in the way that vincristine or Chlormethine does.
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[*] posted on 12-10-2021 at 09:48


Quote: Originally posted by macckone  
Canabinoids at high concentrations over an extended period of time even have their own specific illness:
https://www.cedars-sinai.org/health-library/diseases-and-con...


Very interesting. Big thanks for sharing that.
I have been on sick leave on 5 occasions (20 days total...) this year alone vomiting my guts every 10 minutes. I dont smoke as much as I used to, apparently less than described but this is nevertheless very interesting.
Thank you for sharing that, again.

[Edited on 12-10-2021 by Herr Haber]




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macckone
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[*] posted on 12-10-2021 at 10:09


It does cause nausea and vomiting and cell death of rapidly dividing cells. That is how chemotherapy works. It isn't magic. It is literally toxic to the type of cells found in colon cancer, while less toxic to other cells.

I don't know what the liver damage probability is, but it is listed as a side effect in the trial data. And there are animal studies showing liver damage.

Here is the info on the mouse study:

https://www.healthline.com/health-news/can-cbd-hurt-your-liv...

That study showed toxicity at 100mg/kg.

This article found toxicity at 61.5mg/kg.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928757/

There is definitely hepatotoxicity, meaning in some percentage of the population at therapeutic doses, it will cause liver damage because some people are more sensitive than others.

It is also documented to show nausea and vomiting in the sativex trials but those were not considered serious side effects. That may also have some relationship to the method of administration, spray to the back of the throat.
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[*] posted on 12-10-2021 at 10:31


Quote: Originally posted by macckone  

It is also documented to show nausea and vomiting in the sativex trials but those were not considered serious side effects.

Whereas nausea and vomiting areconsidered serious side effects of conventional cancer chemotherapy.
So, as I said, it's not the same thing.
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[*] posted on 12-10-2021 at 10:51


@macckone: I don't see why toxicity and therapeutic range are relevant for a discussion about solubility of said compound.

What are you trying to say? CBD is toxic? We shouldn't think light of it? I don't get it. Any drug is toxic, any drug has a specific therapeutic range. Any drug probably will cause vomiting.

[Edited on 12-10-2021 by Tsjerk]
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[*] posted on 12-10-2021 at 11:03


Quote: Originally posted by Tsjerk  
@macckone: I don't see why toxicity and therapeutic range are relevant for a discussion about solubility of said compound.
Indeed. macckone, you totally hijacked this thread. Time to split.



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S.C. Wack
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[*] posted on 12-10-2021 at 13:56


Quote: Originally posted by macckone  
https://www.nwsci.com/customer/docs/SKUDocs/RMR/Technical%20...

Pure cbd is used as a chemo agent with all of the usual problems associated with chemotherapy, nausea, vomiting, potential liver damage, etc. Canabinoids at high concentrations over an extended period of time even have their own specific illness:

https://www.cedars-sinai.org/health-library/diseases-and-con...

THC and CBD are relatively benign drugs but they are still drugs and can have side effects.
They still have a much better theraputic margin than many common drugs like ibuprofen and acetominophen (paracetamol)


Quote: Originally posted by macckone  
It does cause nausea and vomiting and cell death of rapidly dividing cells. That is how chemotherapy works. It isn't magic. It is literally toxic to the type of cells found in colon cancer, while less toxic to other cells.

I don't know what the liver damage probability is, but it is listed as a side effect in the trial data. And there are animal studies showing liver damage.

Here is the info on the mouse study:

https://www.healthline.com/health-news/can-cbd-hurt-your-liv...

That study showed toxicity at 100mg/kg.

This article found toxicity at 61.5mg/kg.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928757/

There is definitely hepatotoxicity, meaning in some percentage of the population at therapeutic doses, it will cause liver damage because some people are more sensitive than others.

It is also documented to show nausea and vomiting in the sativex trials but those were not considered serious side effects. That may also have some relationship to the method of administration, spray to the back of the throat.


Sativex is not CBD, and hyperemesis syndrome is presumably not caused by CBD, since you imply that it is.

It's a complete surprise that you of all people are cherry-picking erroneous citations instead of the actual reference, and are citing studies where the dosage is a bit unreasonable, as though such doses are comparable to acetaminophen use. To wit:

"In the sub-acute phase, the eight-week-old mice delivered orally daily doses of 0; 61.5; 184.5; or 615 mg/kg for 10 days. 75% of the mice instantly died at the 61.5 mg/kg dose"

is bullshit in no less than three different ways, as we shall see, as though evidence was needed of the post-truth nature of these times...

This is not to say that the cited Little Rock (Arkansas) U folk don't have an agenda, one can see right away...BTW their main focus is on giving mice the equivalent of 55 g of CBD (not including impurity and solvent weight) a day for 10 days, after finding that a single dose of 221 g was too much:

"Mice at 738 mg/kg and 2460 mg/kg groups developed a sub-lethargic condition which presented as decreased appetite and slow response to exogenous stimuli at 4–5 h after CBD administration. This was still evident in mice receiving the 2460 mg/kg dose at the 24 h time-point...

Shortly after the second gavage with CBD, overt toxicity manifested as profound lethargy, loss of appetite, and body weight loss was observed in 33% of animals (2 out of 6) in the 615 mg/kg group. Two more mice developed similar symptoms after the third gavage. Thus, the remaining four animals were terminated at the end of day 3 (6 h after the third CBD dose). The remaining mice in the 61.5 mg/kg and 184.5 mg/kg cohorts were gavaged as scheduled for 10 days and exhibited no visible signs of toxicity."


55, 66, and 221 g of CBD [whisper][along with 1600, 1900, and 6450 mg THC (effective dose: 5 mg)][/whisper] causes THC-like effects!!! ***STOP THE PRESSES***

[whisper]"Single administration of lower doses (246 mg/kg and 738 mg/kg CBD) caused only increases in liver-to-body weight ratios among the generally liver-focused toxicological responses measured...No measurable toxicological responses associated with liver injury were observed in mice gavaged with CBD at 184.5 mg/kg [daily, the equivalent of 16.6 g/d][/whisper]...In conclusion, the results of these studies demonstrate that, despite the beneficial effects of CBD in the treatment of certain therapy-resistant seizures, it poses a risk for liver injury."

"To our knowledge, the magnitude of such a response has not been observed in previous studies"

Can't come up with a reason why, except that everyone but them are ignorant...so, we should ban every drug that I can't safely take 55 g of daily (plus sesame oil and 40 g of other impurities including 3.6 g which is nearly identical molecularly, but not pharmacologically)?




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[*] posted on 12-10-2021 at 14:17


That are some impressive doses :) what is that? 1000x normal dose? I really don't know anything about cannabinoids. In that range table salt would become lethal.

But really, when you see receptor mediated drugs going into the promille range you have to start wondering whether the effects you are seeing are receptor mediated.
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[*] posted on 12-10-2021 at 15:34


SC Wack,
sativex is a combo of THC and CBD.
It is for epilepsy not chemotherapy.
And yes it caused nausea and vomiting.

The therapeutic dose varies depending on application.
Taking sativex, it is a combo drug of THC and CBD which is 2.5mg per actuation of cbd.
In trials they used 6 actuations serveral times a day and got nausea and vomiting.
Again it was not considered a 'severe side effect' and could be because of the way it is administered but it was more than placebo.
Now that is for epilepsy not chemo.

For epidiolex the dosage is higher and the official website lists the potential side effects:
https://ir.gwpharm.com/news-releases/news-release-details/ep...

EPIDIOLEX may cause liver problems. Your doctor may order blood tests to check your liver before you start taking EPIDIOLEX and during treatment. In some cases, EPIDIOLEX treatment may need to be stopped. Call your doctor right away if you start to have any of these signs and symptoms of liver problems during treatment with EPIDIOLEX:

loss of appetite, nausea, vomiting
fever, feeling unwell, unusual tiredness
yellowing of the skin or the whites of the eyes (jaundice)
itching
unusual darkening of the urine
right upper stomach area pain or discomfort

It is up to 20mg/kg for resistant epilepsy according to the studies.

Devinsky O., Cross J.H., Wright S. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N. Eng. J. Med. 2017;377:699–700. doi: 10.1056/NEJMoa1611618.

Thiele E.A., Marsh E.D., French J.A., Mazurkiewicz-Beldzinska M., Benbadis S.R., Joshi C., Lyons P.D., Taylor A., Roberts C., Sommerville K., et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2018;391:1085–1096. doi: 10.1016/S0140-6736(18)30136-3.

The instantly died at 61.5mg/kg is incorrect, according the the original study.
They put the . in the wrong place, the original is 615mg/kg.
And yes that is a lot of anything to be eating.
Yes I should have dug down to the original study.

Original study:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539990/

The original question I was responding to is why you don't see crystalline CBD sold.
Taking a couple of grams at a time is not going to end well.

For a 50kg person, 20mg/kg is 1000mg or 1gram. Which is the same amount of drug as paracetamol. The safety profile is not that different but it is better than paracetamol.

It is perfectly possible to compound it into pill form instead of 'oil' which is an impure extract.
I believe the Epidiolex is purified using vacuum distillation, but they don't describe how it is made on the website.

So in conclusion even the people that are making money selling epidiolex acknowledge that very high doses can lead to liver issues. And the list of side effects for the drug is pretty consistent with other drugs.

Note that the chemotherapy levels are even higher.
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[*] posted on 12-10-2021 at 17:24


Quote: Originally posted by macckone  
SC Wack,
sativex is a combo of THC and CBD.
It is for epilepsy not chemotherapy.
And yes it caused nausea and vomiting.


In other words, it's not CBD.
It's for MS not epilepsy.
And no it does not cause nausea and vomiting.

Quote: Originally posted by macckone  
For epidiolex the dosage is higher and the official website lists the potential side effects:


Is hyperemesis syndrome on there? "Between January 15, 2014 and January 15, 2015, one clinical trial of CBD enrolled 214 patients (aged 1–30 years) with severe, intractable, childhood-onset, treatment-resistant epilepsy, who were receiving stable doses of antiepileptic drugs before study entry. Oral CBD doses (open label study) of 2–5 mg/kg/day (Epidiolex®, GW Pharma) were up-titrated until intolerance or to a maximum dose of 25 mg/kg or 50 mg/kg/day (dependent on study location and protocol). The adverse events experienced in greater than 10% of the 162 patients in the safety and tolerability analysis were (in order of decreasing frequency) somnolence, decreased appetite, diarrhea, fatigue and convulsion. Serious adverse events occurred in 48 patients (30%), including one sudden unexpected death in epilepsy regarded as unrelated to study drug, and 20 (*12%) patients had severe adverse events possibly related to CBD use, the most common of which was status epilepticus."

How does one explain the FDA approval of Marinol for chemotherapy-related nausea? Not to cause it, but to get rid of it? Not to mention AIDS nausea etc etc.

Quote: Originally posted by macckone  
The instantly died at 61.5mg/kg is incorrect, according the the original study.
They put the . in the wrong place, the original is 615mg/kg.


They didn't die at any dose, instantly or otherwise...they were KILLED (in an unspoken manner).




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[*] posted on 13-10-2021 at 06:27


sativex does include nausea and vomiting as uncommon side effects.

hyperemesis is still being investigated but it is similar to side effects listed for marinol.

Having taken marinol for nausea, I can confirm that if you do not take it as prescribed it can cause nausea on its own. Having stoned people self medicate can lead to people taking pills because they forgot they take pills that cause people to forget they took pills. That is anecdotal but my oncologist confirmed that happens and do not do that.

Here are the side effects of marinol:
Side Effects

Dizziness, drowsiness, confusion, feeling "high", an exaggerated sense of well-being, lightheadedness, nausea, vomiting, or stomach/abdominal pain may occur as your body adjusts to the medication. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.
https://www.webmd.com/drugs/2/drug-9308/marinol-oral/details
side effects list are on the second page.

The stomach/abdominal pain is very similar to the reported syndrome.
Paradoxical effects in medications are not at all uncommon.

If you look at the original paper, they do say that animals died during the gavage.
Possibly as a result of inhaling liquid. I don't think it is relevant to the potential for liver damage which is listed as a side effect of the pure CBD medication.

Part of any analysis of a medication is determining what levels cause damage.
Even water will kill you if you take too much. In the water case, the mechanisms are well understood. In THC and CBD, the potential problems are still being discovered. THC does not appear to cause liver damage, CBD does. THC doesn't kill cancer cells, CBD does. It is interesting that taking CBD for epilepsy can cause dangerous episodes in some patients.
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[*] posted on 13-10-2021 at 14:43


Quote: Originally posted by macckone  
If you look at the original paper, they do say that animals died during the gavage.


Have you ever taken a drug and later realized that for a few hours, you were honest?

BTW from "Cannabidiol Adverse Effects and Toxicity" Curr Neuropharmacol. 2019 Oct; 17(10): 974–989

In humans receiving the drug for the treatment of epilepsies and psychiatric disorders, the most common AEs included tiredness, diarrhea, nausea, and hepatotoxicity. Overall, the incidence of these occurrences is low and, in comparison with other drugs employed for the treatment of these diseases, CBD has a better side effect profile.

No one will be taking any massive doses of CBD unless they grow it on a large scale. It's not cheap.

PS CBD is more bioavailable in mice than humans, making the above dosing even more insane.

For the treatment of cancers, it's probably best to inject cannabinoids natural or otherwise (although all unnatural unprescribed "cannabinoids" psychoactive or not are highly illegal in many cities/counties/states) as close to the affected area as possible, in some acceptable solvent.

[Edited on 13-10-2021 by S.C. Wack]




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macckone
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[*] posted on 14-10-2021 at 07:39


SC Wack,

We already established CBD has a good safety profile way back in the thread.

Way back in my first post:

"THC and CBD are relatively benign drugs but they are still drugs and can have side effects.
They still have a much better theraputic margin than many common drugs like ibuprofen and acetominophen (paracetamol)"

The chemotherapy doses are 'massive', ie. higher than for epilepsy, which does include 'massive' doses, ie 1000mg.

Chemotherapy is usually (but not always) an adjunct therapy after the tumor is removed to kill metastatic cells elsewhere. So injecting it 'close to the affected area' isn't really a thing outside of inoperable tumors. Having been through this personally (anecdotal but still relevant), anything that reduces side effects is going to be good for patients. Coding during treatment is not pleasant.

As for cost, CBD powder is $1450/kg and comes out to $1.45 a dose at 1000mg. Compared to something like oxaliplatin that is really cheap.

Crude CBD oil is about a pound per plant, that is somewhere around 10% CBD. Which is about 40g or so of pure CBD per plant. So no, you don't have to have a large scale operation to get a lot of CBD. A home grow operation in colorado allows 6 plants per adult. That comes out to 240g per adult of pure CBD. That is right at the limit of what a single adult can consume in relative safety. If you tried smoking that much weed, you wouldn't be doing much else.

Keeping in mind that a strain like harlequin is producing CBD:THC in a 5:2 ratio and there is a lot of crud in crude CBD oil.
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[*] posted on 14-10-2021 at 15:48


I do wonder what treatment options are available for your cancer...everything you type is pathological disrepresentation.

What little CBD usage in human cancer there has been so far has actually involved injecting CBD into the area. BTW there are no cancer-related human clinical trials of CBD in the USA at this time. There is "A Long-term Safety Study to Assess the Potential for Chronic Liver Injury in Participants Treated With Epidiolex (Cannabidiol) Oral Solution"

PS if someone unlicensed to do so grows 6 <0.3% THC Cannabis plants indoors around here for any reason and anyone else finds out about it, they'll end up sentenced to 5-10 years in prison, or more if they say that it's for someone else. If there's children, they won't be seen again for a long time. A gun of any sort could turn the case federal (even bullets can get federal sentencing nowadays). Throw in An Extraction Lab!!!

(avg 6-plant indoor = 300-600 g total, x 10% / 100 d = 300-600 mg/d)

(kilos can actually be bought for less but I'm not talking about buying kilos)




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[*] posted on 14-10-2021 at 19:51


Quote: Originally posted by Tsjerk  
That are some impressive doses :) what is that? 1000x normal dose? I really don't know anything about cannabinoids. In that range table salt would become lethal.

Studies demonstrating effects of CBD in controlling tumors typically use incredibly high doses by the standards of a smoker. 300-600 mg seems common, where a typical CBD edible offers about 20 mg.

I've read a few of these studies and the gist that I've gotten is that very-high-dose CBD does produce some measurable amount of tumor control, but it doesn't generally eradicate tumors. Where it is promising is in the ability to extend life for patients where standard regimens have failed and the patient may not be able to tolerate other treatments; it works by a novel mechanism and evades the resistance that tumors build up to common antiproliferative agents. But it's more of a time-out than a Hail Mary.

The figure of merit for an antitumor medication is the differential cell toxicity, i.e. the toxic level for normal cells divided by the toxic level for tumor cells. While the therapeutic ratio for CBD in managing anxiety etc is very high, at cancer-relevant doses it becomes much lower.

For really promising cancer treatments, see e.g. halomon or bromopyruvate.

Sorry, I didn't really read the whole thread, but I've turned the hourglass plenty of times reading about cannabidiol and cancer. (I have recently been treated for cancer.)




[Edited on 04-20-1969 by clearly_not_atara]
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[*] posted on 14-10-2021 at 23:49


You can either say
"THC and CBD are relatively benign drugs"
Or you can say
"Pure cbd is used as a chemo agent with all of the usual problems associated with chemotherapy".

But you can't say both.
Because the usual problems with chemotherapy drugs make them anything but "benign".
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[*] posted on 15-10-2021 at 07:02


Unionized,

Dose is everything. That is why I included the word "RELATIVELY".

At 60mg a day they are benign.
Compared to something like oxaliplatin (FOLFOX treatment) at 85mg/week, they are relatively benign.
when taken pure in chemo quantities 1000+mg a day, they are like every other chemotherapy.
They also have better safety profiles, ie. THC will not kill you as far as anyone has been able to determine.
And CBD has a better safety profile than paracetamol for liver damage but not for nausea and vomiting.

SC Wack,

FOLFOX is the standard treatment for colon cancer (leucovorin, fluorouracil and oxaliplatin).
I can no longer have that treatment if I have a recurrence and the last half of my treatment was xeloda which is less effective but doesn't put me into cardiac and pulmonary arrest.
I was on a bunch of adjuvenant therapy with the xeloda and I got a ton of marinol generics during both phases.
Puking your guts out for over a year is not fun. And I mean that literally, you vomit up stomach lining.
The vomiting also destroys the enamel on your teeth too.
There are no currently licensed trials, of CBD only products for chemo. There was an off-label trial of sativex but the dose of THC was too high to get the CBD concentrations needed. It did prove effective in pain and nausea relief at lower doses than what was proposed as tumor suppression. I don't know if that every got fda approval as a 'use'.

clearly_not_atara,

Sorry about your bout with cancer. It sucks.
My only experience with halomon is living near the coast with red tide.
Breathing it sucks.


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[*] posted on 15-10-2021 at 12:34


Quote: Originally posted by macckone  
Unionized,

Dose is everything.



No, Therapeutic Index is everything.
And carcinolytics usually have really bad TI whereas CBD has a much better one.

as you say "THC will not kill you as far as anyone has been able to determine."
Well arsenic trioxide or cisplatin or whatever certainly will.
That really is a distinction.

Obviously, enough of anything, even water, will kill you.
I'm unaware of any data on human CBD lethality in a well controlled situation.
But there's quite good data on monkeys.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052834/

They survived doses up to 300 mg/kg/day for 90 days equivalent to a total of nearly 2000 grams in a human. (No, I don't mean milligrams)


There were toxic effects that those doses, but no fatalities

That much acetaminophen would certainly kill you.


[Edited on 15-10-21 by unionised]
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macckone
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[*] posted on 16-10-2021 at 10:54


You clearly did not read that link thoroughly. The monkey study determined an ld50 of something a little over 210mg/kg and it was 9 days not 90
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S.C. Wack
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[*] posted on 16-10-2021 at 13:59


Everything is clear all right.

From the abstract:
"Ninety-day oral treatment with CBD (30-300 mg/kg) had little effect but liver and kidney weights rose 13-56% above controls without morphologic changes."



[Edited on 17-10-2021 by S.C. Wack]




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macckone
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[*] posted on 16-10-2021 at 14:35


In 1981, Rosenkrantz and Hayden investigated acute cannabinoid toxicity in rhesus monkeys following 150, 200, 225, 250, or 300 mg/kg intravenous (IV) CBD for 9 days [61]. The LD50 was 212 mg/kg CBD. Tremors were observed at all doses and CNS inhibition (depression, sedation, and prostration) was evident within 30 min

https://scholar.google.com/scholar_lookup?journal=Toxicol.+A...


[Edited on 16-10-2021 by macckone]
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