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The "Entourage Effect"

Mafioso

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Is it real, or mostly just hippy babble? Assuming quality and other variables have been removed, does each strain posses a unique enough blend to create a experience that is notably different than another, assuming quality and other variables have been removed?

Based on my own anecdotal evidence, I have always been skeptical of these claims. I know that doesn't prove anything, but it always seemed more than plausible to me that the wide range of experiences can mostly be attributed to individual physiology and psychology. Mostly the individual's neurochemistry and how one thinks and reacts to this.. if that makes sense.

People point to studies done on individual isolated terpenes and assume that because that is the function it has when isolated terpenes are inhaled, that it must play the same role when smoke, eaten, or vaporized and combined with other terpenes and cannabinoids. Some even take it a step further and assume that they will even have synergistic effects on one another, but I have yet to see evidence of this beyond CBD and THC's interaction, which when looking at how THC lowers the threshold for CBD to be effective, it could be said the two are synergistic in at least one way.

Without evidence, I can not make claim either way, but it appears that most arguments for the entourage effect seem to make an appeal to anecdotal evidence, and all seem arguments seem to appeal to ignorance or complexity. The most honest answers seem to be along the lines of "we aren't totally sure yet".

Does anyone with experience in neuroscience or pharmacology have any insight? I want to be open to whatever the truth might be, but the more I hear bad arguments for something the more I am inclined to believe the opposite, which isn't necessarily true either. I know it's not all entirely intuitive either, as the relationships can become very complex. It just seems to me that much of what people believe to be the entourage effect is really just placebo.
 

emkee_reinvented

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Very curious about it to but sorry to say I have not done any experimenting with entourage effects. Did Mango/ mycrene and Absinth tea without noticable effects. But the combination below is said to boost the high up a few nodges.

"with Rosewood, Clary Sage and Mastic for drastically boosting your Cannabis. The effect of your Cannabis is enhanced (boosted) in a way you have never experienced before. The feeling comes faster, stronger, more intense and lasts longer then without.
Taste/Scent: Sweet, Pine Cedar, Woodsy.
Ingredients: Rosewood, Clary Sage, Mastic.
May Be Useful For: Boosting the effects already present in your Cannabis*"
 

AlphaMethylPhenyl

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It's real. There is a synergism in the cannabinoids, as well as with the terpenes. Some have similar mechanisms of action. In a rough analogy, think of two downers with different mechanisms but both increasing GABA levels (which I don't recommend, but just for the sake of analogy).

So CBC and CBG can both be effective against pain, but I doubt they work in the exact same manner. This is an example.

THC and CBD are the only appropriately-analyzed cannabinoids, and yet still haven't been tested much. There are estimates of 60 to over 100 cannabinoids in the plant. Welcome to part of the future of psychiatry and medicine.

Think too of the past two decades or so during which THC levels have been maximized at the expense of CBD and other chemicals in the plant. Otherwise, CBD would cancel out this large propensity for psychosis, and both THC and CBD would both raise mood in a less hallucinogenic manner, as they are known for raising mood.

The terpenes haven't been analyzed much, either. The financial incentive isn't there. But they're important, nonetheless.
 

G_Chem

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I have been “testing” this for the past 15yrs and now with recreational access I’ve been able to take the time to really get to know certain strains. Yes this indeed not bullshit..

I will say that the differences in effects are often exaggerated but nonetheless the differences are there.

For instance.. Forbidden Fruit has become a staple for me as the perfect stoning night time smoke. If I don’t have this strain my sleep will go to shit for a few days even with plenty of other strains available.

I can tell if a strain is high in THCV just by the high an terpene profile.

I’ve been able to really put some of this to the test and it’s held up fairly well. For instance, I found that high quality AK-47 is amazing for headaches by accident when I had one and it was completely relieved for a few hours from a few hits.

My dad also suffers from bad headaches so without saying a word I gave him some one night. The next day he came to me and was ecstatic at how well it had cured his headache the night before.

AK-47 is interesting though and further shows the variation because the analgesic effect feels all in the head and nowhere else. Othervstrains have much more bodily analgesic effect.

I myself smoke all day every day, only one hit at a time out of a one hitter. I usually buy a half oz or oz of a strain and have 4-5 on me or more at any given time. Just to give perspective.. This allows me the time and variation of strains to find what works best for me and when.

I’ve found this “entourage effect” is applicable to just about every psychoactive substance found in nature. Different cacti have different effects, same with mushrooms, DMT plant sources, you name it..

-GC

Oh also I have experimented with pure 99.9% THCA as well as isolated terpenes with only a small amount of cannabinoids left in it. (It was a strain similar to Blueberry.) The isolated terps actually got me really high and gave the body stone, munchies and many of the things I associate with cannabis high. The pure THCA just gave the “feel good” mental part of that makes any sense.

-GC
 

Mafioso

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I don't mean to be rude, but I'm really not looking for more anecdotal reports and unsubstantiated claims.
two downers with different mechanisms but both increasing GABA
I know you said rough analogy, but this to me seems like flawed logic, or at the least an oversimplification. I understand what may be possible, I am asking how. Two opioids doesn't necessarily have synergistic effects, or at least not intuitively.(i.e. buprenorphine).
THC and CBD are the only appropriately-analyzed cannabinoids, and yet still haven't been tested much
This seems like bit of a contradiction itself, but if it is true that they are the only cannabinoids that have been studied enough, then how can you make any claims about any cannabinoids other than those 2? I'm not familiar with the work myself, but I have been told that cannabis in general has been studied pretty extensively in other countries. Israel gets mentioned a lot.

Think too of the past two decades or so during which THC levels have been maximized at the expense of CBD and other chemicals in the plant.
This is mostly a myth as well, as not all breeders select for the same traits as each other or even the same traits for every variety. Also, not all breeders are commercialized and there is a huge craft and hobby market. Not to mention the explosion of high CBD strains from the current and on going hemp rush, which literally breeds the opposite(high cbd and low thc). Also, with the advancement in extracts this argument is pretty much entirely void, as we can isolate cannabinoids fairly well now and we are only getting better.

CBD would cancel out this large propensity for psychosis,
Citation? I know there is at least one study that shows reduced risk of psychosis but it to say it cancels out would be an overstatement. I believe the mechanism is CBD's mild CB(1/2? not sure) antagonism but I don't have a source for that, so I can't say for certain. EDIT:CBD & CB1&2 <-relevant but not conclusive or about psychosis.

THC and CBD would both raise mood in a less hallucinogenic manner, as they are known for raising mood.
This is a confusing statement to me, as it seems to imply that to presence of one changes the function of the other. I would like to see the citation on this, as I don't think it's entirely true. Reduced risk of psychosis isn't necessarily a less hallucinogenic. But maybe I am being too analytical of your statement, as some interpretation can be said to be true.

The financial incentive isn't there
Not true at all... take a look at the massive amounts of terpene companies marketing terpene blends specifically to cannabis business and consumers.(i.e. True Terpenes, Floraplex Terpenes, and the literal thousands of other companies that are selling terpenes at an insanely high mark-up).

So CBC and CBG can both be effective against pain, but I doubt they work in the exact same manner.
Source? How can any claims about effectiveness be made without considering dose? You wouldn't' say 1-2 picograms of advil is effective against pain. Even in strains that contain high levels of these, they are still relatively minute amounts. Also, your point about the THC being selectively bred out is moot when considering that cannabinoids are essentially different isomers of each other and can be created in a lab. CBD can be isomerized to THC, and much much more.

Again, I'm not trying to be rude or attack you, but I am really trying to put to bed a lot of these myths that are being perpetuated as truth. If cannabinoids or cannabis in any form is ever to fully transition into the medical world, these things will need to be considered.

Mango/ mycrene and Absinth tea without noticable effects. But the combination below is said to boost the high up a few nodges
The mango/myrcene is the sort of myth I'm wanting to put to rest. If it were true, then eating fruits and salads would all have similar modulations. I'm not really looking for a way to get higher anyways, I want to understand what is going on here. We have no way of telling if that way actually works, so even if it does it doesn't do a whole lot for furthering the understanding. Mostly just more anecdotal claims to add to the pile.

Yes this indeed not bullshit..
So you say, but you also say the effects are often exaggerated. How do you know it is not placebo you experience, or the result of other factors?

can tell if a strain is high in THCV just by the high an terpene profile.
I'm not sure how you can do that, as the machines that do test for potency are highly sensitive and need to be carefully calibrated. Considering how low most strains are in THCV, you must be extremely sensitive and have a good way at detecting errors...? And can you explain the relation between THCV and the terpene profile?

If I don’t have this strain my sleep will go to shit for a few days even with plenty of other strains available.
There isn't really one strain on the market that posses any traits so unique that it can be said no other strain has it. Many strains are closely related, just different phenos. That's not to mention how often strains get mislabeled and intentionally renamed. Considering how similar most strains are in chemical composition, and how many strains have profiles that are not that different from the one you mention, I don't understand how it can be giving you such drastically different experiences. Unless of course the placebo/nocebo are taken into account.

I have experimented with pure 99.9% THCA as well as isolated terpenes with only a small amount of cannabinoids
You saw the lab results of 99.9% pure? Or that's what you were told/it said on the label?
“feel good”
This term is so subjective that it, and ones like it, could explain a large portion of the variance in reported experience. I'm looking to understand by what mechanism these things give us that "feel good".

I appreciate the responses, I really do, but I am wanting to have a scientific discussion as much as possible and with all the anecdotal claims flying around we really don't need a thread that compiles more of them. I'm looking to either prove or disprove these claims, not make more of them. I've been involved in the medical marijuana industry in CA for the last decade, and am very well versed and familiar with most all of them. The thing that I've noted that is prevalent among these claims is the lack of evidence. If there is a study cited, it is often taken out of context.

I suppose I should have led with this article, but here is one that does a better job of summarizing the situation.
Entourage Effect Scientifically Valid
"Haney says she has only seen evidence against the entourage effect. In recent studies (including Haney’s own) directly comparing the effects of plant marijuana with oral THC formulations such as Marinol and Syndros, the results suggest there is little—if any—difference between them."

Also:
Absence of Entourage Effect
"None of the six of the most common terpenoids in Cannabis directly activated CB1 or CB2, or modulated the signalling of the phytocannabinoid agonist Δ9-THC. These results suggest that if a phytocannabinoid-terpenoid entourage effect exists, it is not at the CB1 or CB2 receptor level."

I will update with relevant studies as I read through them. I currently have about 15 tabs open.
(Updated 10:31 PCT )
 
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AlphaMethylPhenyl

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Sorry for the tricky presentation. Not intended.

I don't mean to be rude, but I'm really not looking for more anecdotal reports and unsubstantiated claims.
I don't proffer such claims.

I know you said rough analogy, but this to me seems like flawed logic, or at the least an appeal to ignorance. I understand what may be possible, I am asking how. Two opioids doesn't necessarily have synergistic effects, or at least not intuitively.(i.e. buprenorphine)
No when I talk of synergism it isn't by the same mechanism, as stated. A GABA PAM and a GABA POM more specifically would abide by what I stated in terms of synergism.

This seems like bit of a contradiction itself, but if it is true that they are the only cannabinoids that have been studied enough, then how can you make any claims about any cannabinoids other than those 2? I'm not familiar with the work myself, but I have been told that cannabis in general has been studied pretty extensively in other countries. Israel gets mentioned a lot.
No, cannabis hasn't been studied much at all. Recently, it has been more so, but it had all of the red tape of Schedule I status basically everywhere for so long. Preliminary studies on CBC and CBG show painkilling effects.

This is mostly a myth as well, as not all breeders select for the same traits as each other or even the same traits for every variety. Also, not all breeders are commercialized and there is a huge craft and hobby market. Not to mention the explosion of high CBD strains from the current and on going hemp rush, which literally breeds the opposite(high cbd and low thc).
Common knowledge that things are mostly as I say, beside the relatively recent mainstream attention of CBD.

Citation?
I see a database in your future.

They are both known to be anxiogenic in case studies as well, including the beloved CBD.
Most anything *can* cause anxiety, but CBD? No, not believable.

Not true at all... take a look at the massive amounts of terpene companies marketing terpene blends specifically to cannabis business and consumers.(i.e. True Terpenes, Floraplex Terpenes, and the literal thousands of other companies that are selling terpenes at an insanely high mark-up).
Marketing them isn't the same as well-done, recent, double-blind, randomized, controlled experiments on mechanisms and medical potential.

Source? How can any claims about effectiveness be made without considering dose? You wouldn't' say 1-2 picograms of advil is effective against pain. Even in strains that contain high levels of these, they are still relatively minute amounts. Also, your point about the THC being selectively bred out is moot when considering that cannabinoids are essentially different isomers of each other and can be created in a lab. CBD can be isomerized to THC, and much much more.
And yet otherwise CBG/CBC can be worked with to raise the amount made by the plant, as can THC/CBD levels be after clever breeding.

Bred out? I was (at least trying to talk) about THC levels being raised way high up in the last few decades.

Again, I'm not trying to be rude or attack you, but I am really trying to put to bed a lot of these myths that are being perpetuated as truth. If cannabinoids or cannabis in any form is ever to fully transition into the medical world, these things will need to be considered.
No need to apologize.
 

G_Chem

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I’ve placebo’ed myself before. Placebo is 100% possible that’s why the strain needs to be tried many times, over many days, to better understand it.

The time which I placebo’ed myself I was given what I thought was zolpidem from my mother, completely confident they were legit. First night 90% effects, almost identical. Second night 30% effects, very confused on the tolerance but pushed it off. Third night, maybr 5%. It was then that I decided to check the tablets to find they were something else, completely inactive.

I believe you can get placebo’ed for awhile but the true effects will eventually shine.

As for the exaggerated claims, that is mainly dependent on who your talking to and what effects are being talked about. That answer is a big “it depends.” Not all are exaggerated, some are.. We’d need to get specific to talk more on the subject. Some people believe cannabis is a panacea, I’m not one of those but it’s miracle nonetheless.

As for the 99.9% pure THCA... With the crazy amount of regulation and competition on the emerging cannabis industry, most don’t fuck around as getting caught in a lie is the end of your business.

I will admit percentages for flower can be easily altered or wrong based on multiple factors but with extracts that is rarely the case. This substance was a clear crystalline substance purchased in one of the most reputable shops in the country.

By “feel good” I meant it felt very much like it was effecting the dopamine portion of my brain. It was fairly stimulating and tasted odd from memory. Gentle in a way though too, like it was missing something.

One thing I noticed too, I get feeling really shitty when I stop use of certain cannabis products. Like if I eat cannabis edibles for a few days then stop, I’ll have zero sleep, nausea, and generally feeling ill as a rebound/withdrawal effect. The pure THCA didn’t effect me in this way, just mild irritation during cessation.

I know you want “scientific studies” but your not gonna get many if any. I’ve looked around and all I’ve found is the same anecdotal information I’m spewing at you now. There just scratching the surface on the other cannabinoids let alone studying terpenes and their interactions to any great deal. Right now much of what we have to go on is people’s experience and we should never discard that as worthless.

Regarding THCV, yes I can feel it. Reason being, it can give me headaches if I smoke too much of it. I like strains that contain it but it has a slight edge to it that builds if I overuse. There seems to be a terpene profile that lots of THCV strains have, likely because they all come from the same South African lineage. Durban Poison being kinda the basis for the smell. I suppose there’s other things that could be happening with this instance though, such as a particular terpene being common amongst all the same strains as well which has said effects.

One final word on the subject.. I’ve noticed that when I smoke cannabis that has low to no terpene profile due to one of many reasons, the effect is very one dimensional. It all gives me a much similar high. It’s not til I start messing out with high quality terpene heavy buds do I notice the nuances.

I look forward to seeing all these studies your waiting on.

Edit- I should note I have tested many weird strange substances on myself over the years. Done some bioassays on fairly exotic materials. I’m willing to accept my ability to differentiate is probably a bit better than your average.

-GC
 
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Mafioso

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AMP, I'm not sure how I can take any of your claims seriously. Your rebuttals are pretty much just "your wrong, I am right", you provide no source or reasoning. I point out how can you make claims about the efficacy of specific cannabinoids while also stating that it is understudied? Instead of admitting to overstepping in your claims, you return with more unsubstantiated claims about preliminary trials. At what doses though? Assuming what you say is true, we still don't know if the amount typically found are even enough for a threshold dose.
I keep asking for sources because all that I see only state things like "potential" and "pre-clinical studies", so someone who talks about professionalism in the mental health field, I would think you'd understand the relevancy of my point about making such frivolous claims.

And I may have overstated my point about CBD being anxiogenic. I can not find any reference on it being anxiogenic, I was repeating the words of Dr. Drew from this podcast. Again, I question how you can state it is understudied while also making any claims. Seems like perpetuating the ignorance to favor your argument. The nice thing about science is it that you don't have to believe it for it to be true. Many anxiolytics have anxiogenic side effects.

Most are quick to assume the supposed positives, but are in disbelief at possible negatives.
Low doses of widely consumed cannabinoids (cannabidiol and cannabidivarin) cause DNA damage and chromosomal aberrations in human-derived cells
 
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Mafioso

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"Common knowledge that things are mostly as I say, beside the relatively recent mainstream attention of CBD"
Sorry, but this is just pure arrogance. You are repeating myths perpetuated by articles like hightimes. Common "knowledge" = common beliefs, and depending on what circle you are standing in, they may not be common at all. If you had any point to your argument you would put it forward rather than just trying to assert you are right.

" But cannabis breeders (often working illegally in the past) have long been crossing plants to develop distinctive strains that purportedly do different things, and breeders are using genetics to make that process more precise and efficient. “We have a huge set of cannabis genomic data that will, hopefully, allow us to ID genetic markers associated with chemical results and certain patient outcomes,” Holmes says. “We’re just getting started.” "

Spend some time on ICMag.com or Future4200.com and you will see that things are far from as you say, at least about "the past two decades or so during which THC levels have been maximized at the expense of CBD and other chemicals in the plant". That sounds like something you'd find on the headlines of FOXNews or CNN. You don't have to spend much time in the scene to notice that there is a huge obsesssion with terpenes, CBD, and cannabinoids other than THC. High THC concentrates that are devoid of other compounds are generally stigmatized, as the prevalence of the entourage myth is so strong.
 
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Hylight

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the "entourage effect"
Seven leaves
with hazes in
the sea of
green blazes.
 

Mafioso

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I’ve placebo’ed myself before. Placebo is 100% possible that’s why the strain needs to be tried many times, over many days, to better understand it.
That isn't really how placebo works. Without double blind testing it is pretty much impossible to rule it out.

Placebo is basically physiological effects(real or perceived) generated by psychological means. A good example is when testing depression drugs, a certain number of patients will report improvements even though they were only given a sugar pill in place of the real drug.

This article here does a great job of explaining it better than I did. It compares 2 groups of pain patients, one group given painkiller, the other given acupuncture. A third report serious side effects, and surprisingly more people in the acupuncture group report improvement. However, "The study wasn’t aimed at comparing two treatments. It was designed to compare two fakes."

As for the 99.9% pure THCA... With the crazy amount of regulation and competition on the emerging cannabis industry, most don’t fuck around as getting caught in a lie is the end of your business.
Lab in california caught falisfying results
From a chemistry perspective, 99.9% sounds like a made up number. I guess they could have got 99.9xx% back from the lab, but it's pretty fishy. I've seen a multiple lab results show over 100% cannabinoids, so obviously there is something going on there. I don't really care to get into that conversation here. Regardless of the accuracy of those numbers on the label, you can't verify them yourself unless you send them in for testing or have access to a HPLC or GC.


purchased in one of the most reputable shops in the country
Appeal to authority, but assuming it is true, it is still anecdotal and set up in a way where placebo/nocebo will be strong. It's pretty much impossible not to have an expectation when taking any drug.

I get what you are saying, and I don't disagree with it entirely, but what you describe isn't science it's just experimenting.
 
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Mafioso

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I added some links to my post earlier. One is an article from Scientific American that, in my opinion, does a pretty good job of summarizing the current situation. The second is a study done by biorxiv, entitled "Absence of entourage: Terpenoids commonly found in Cannabis sativa do not modulate the functional activity of Δ9-THC at human CB1and CB2 receptors".

I suppose I should clarify some semantics as well. I am coming from a purely skeptical position in reference to the "Entourage Effect". I am completely open to the idea and possibility that that is an interaction between certain compounds in cannabis, however, far too many unsubstantiated claims are made based on this possibility. If you want to make a claim in favor, please provide evidence not speculation. And be specific about your claims. I know this might seem pedantic, but it seems necessary with the abundance of anecdotal claims. I have my own, which contradict others, so clearly we need a better standard of evidence.

I'd rather stick to debating the facts rather than each other, and if we do get to a point where we have established all the known facts while still being unable to determine exactly what/why is possible, then I'd gladly conclude to agree we don't know and more research is needed. I'm not against anecdotal or even speculation, but I'm looking to unblur the lines first.

Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis
"Severity of psychotic symptoms was directly correlated with inhibition error frequency and inversely with inhibition efficiency under the influence of delta-9-THC. Delta-9-THC attenuated left inferior frontal activation which was inversely correlated with the frequency of inhibition errors and severity of psychotic symptoms and positively with inhibition efficiency under its influence. These results provide experimental evidence that impairments in cognitive processes involved in the inhibitory control of thoughts and actions and inferior frontal function under the influence of cannabis may have a role in the emergence of transient psychotic symptoms under its influence"

So, based on this study, it appears that D9THC and psychosis are related to the level of impairment it causes to the inhibitory control process.

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders
"In addition to its low and variable oral bioavailability in humans [135], it causes bell-shaped dose-response curves and, judging from the studies with laboratory animals, possesses a narrow therapeutic dose range."
This quote highlights the importance of considering dose when talking about the efficacy of a drug, CBD in this case. Really, all claims would be dependent upon dose as even water and oxygen become toxic at high enough levels. Below threshold dose, the major effect will be the placebo.

There does seem to be quite a bit of evidence for the "entourage/synergistic effect" of CBD and THC:
Cannabis with high cannabidiol content is associated with fewer psychotic experiences.
"We found a significant inverse relationship (F(1,1877) : 14.577, p<0.001) between cannabidiol content and self-reported positive symptoms, but not with negative symptoms or depression. The estimated effect size of cannabidiol content was small." "Although the observed effects are subtle, using high cannabidiol content cannabis was associated with significantly lower degrees of psychotic symptoms providing further support for the antipsychotic potential of cannabidiol"

CBD-rich extracts seem to present a better therapeutic profile than purified CBD, at least in this population of patients with refractory epilepsy
"This meta-analysis paper describes the analysis of observational clinical studies on the treatment of refractory epilepsy with cannabidiol (CBD)-based products. Beyond attempting to establish the safety and efficacy of such products, we also investigated if there is enough evidence to assume any difference in efficacy between CBD-rich extracts compared to purified CBD products. " "The categorical data of a total of 670 patients were analyzed by Fischer test. The average daily dose ranged between 1 and 50 mg/kg, with treatment length from 3 to 12 months (mean 6.2 months). Two thirds of patients reported improvement in the frequency of seizures (399/622, 64% ). There were more reports of improvement from patients treated with CBD-rich extracts (318/447, 71% ) than patients treated with purified CBD (81/223, 36% ), with statistical significance (p < 0.0001)" "...when the standard clinical threshold of a "50% reduction or more in the frequency of seizures" was applied, only 39% of the individuals were considered "responders,"..." "Patients treated with CBD-rich extracts reported lower average dose (6.1 mg/kg/day) than those using purified CBD (27.1 mg/kg/day). The reports of mild (109/285 vs. 291/346, p < 0.0001) and severe (23/285 vs. 77/346, p < 0.0001) adverse effects were more frequent in products containing purified CBD than in CBD-rich extracts. "

This study has provided the first evidence that cannabidiol can display CB2 receptor inverse agonism, an action that appears to be responsible for its antagonism of CP55940 at the human CB2 receptor
"We have shown previously that cannabidiol can enhance electrically evoked contractions of the mouse vas deferens, suggestive of inverse agonism. We have also shown that cannabidiol can antagonize cannabinoid receptor agonists in this tissue with a greater potency than we would expect from its poor affinity for cannabinoid receptors." "The ability of cannabidiol to behave as a CB2 receptor inverse agonist may contribute to its documented anti-inflammatory properties."

Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol
" In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses." "It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD. We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions."

Cannabis-based medicines--GW pharmaceuticals: high CBD, high THC, medicinal cannabis--GW pharmaceuticals, THC:CBD.
"includes investigations in the relief of pain of neurological origin and defects of neurological function in the following indications: multiple sclerosis (MS), spinal cord injury, peripheral nerve injury, central nervous system damage, neuroinvasive cancer, dystonias, cerebral vascular accident and spina bifida, as well as for the relief of pain and inflammation in rheumatoid arthritis and also pain relief in brachial plexus injury." " GW stated in its 2002 Annual Report that it was currently conducting five phase III trials of its cannabis derivatives, including a double-blind, placebo-controlled trial with a sublingual spray containing High THC in more than 100 patients with cancer pain in the UK. Also included is a phase III trial of THC:CBD (narrow ratio) being conducted in patients with severe pain due to brachial plexus injury, as are two more phase III trials of THC:CBD (narrow ratio) targeting spasticity and bladder dysfunction in multiple sclerosis patients."

The fact that GW Pharm was already studying this in the UK back in 2002 leads me to believe it isn't as mysterious as some might propose, as it has been studied for decades despite its illicit status. Also, being that they were already focused in on THC and CBD in combo to treat pain seems to suggest that it is mostly CBD and THC responsible for pain relief. It doesn't rule out the potential of others, as their focus could be for logistic reasons as THC and CBD are the most prevalent.




More evidence suggesting it is still too early to make claims about cannabinoids beyond THC and CBD:
Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures
"the exact mode of action of major phytocannabinoids has to be elucidated, but both, receptor and non-receptor mediated effects are discussed. Focusing on the often presumed structure–affinity-relationship, Ki values of phytocannabinoids cannabidiol (CBD), cannabidivarin (CBDV), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN), THC acid (THCA) and THC to human CB1 and CB2 receptors were detected by using competitive inhibition between radioligand [3H]CP-55,940 and the phytocannabinoids." "Most of the phytocannabinoids did not affect the number of dopaminergic neurons in primary cultures, whereas propidium iodide and resazurin formation assays revealed cytotoxic properties of CBN, CBDV and CBG." "THC showed positive effects on N18TG2 cell viability at a concentration of 10 μM, whereas CBC and THCA also displayed slightly positive activities. These findings are neither linked to structural characteristics nor to the receptor binding affinity therewith pointing to another mechanism than a receptor mediated one."

OK, that's enough for today. I will continue tomorrow.
 
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Mafioso

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Thank you, SJP.

I didn't get to any research today. I want to review this study and also take a closer look at GW Pharm's Sativex in hopes of gaining some insight on the efficacy of CBD with and without the presence of THC. I have seen a lot of claims about the average male needing around 500mg dose of CBD isolate for it to be effective, where as the threshold dose is lowered to something like 20mg with both CBD and THC. At least one of the studies in my last post also pointed to this fact.

Also, while speaking with a chemist who works with cannabinoids, I learned that it is theoretically possible to synthesize any cannabinoid, and many known synthesis for cannabis based cannabinoids from common terpenes are already available to the public. That is to say, forego legalities, it would be relatively simple to study. One might not even need to grow any cannabis plants with the right chemist on board.

But for now, I will stick to reviewing what has already been published on the subject.
 

Mafioso

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More evidence against the entourage effect, or at least terpenes role in it.
"we investigated potential changes in the chemical and biological proprieties of BC after exposure to C. sativa smoke (CSS). Our results showed that the BC exposed to CSS underwent 98.8% degradation and suffered loss of its antiradical activity."
BC being the terpene beta-carotene.
 

w01fg4ng

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Terpenes are also synergistic when paired with complimentary foods.
 

w01fg4ng

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Personal experience.

It's a harmony of tastiness and pleasure in every meal.
 

Mafioso

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ah, anecdote. so no evidence whatsoever, not even a suggestion at the potential mechanisms… just more perpetuation of unsubstantiated claims....

this is exactly what I'd like to keep out of this thread. Thank you for that.
 

AlphaMethylPhenyl

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Easy enough to do a trial. Take pure CBD or pure THC and compare the effects to CBD hemp or marijuana. If you look at the mechanisms of the phytocannabinoids and terpenes you'll find that they overlap, which unless they work in exactly the same manner, will mean that there is synergy (given that the whole plant doesn't feel or produce the effects of CBD and/or THC).
 
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