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The Entourage: One Of The Many Missing Pieces To The Puzzle


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  • 3 weeks later...
  • 3 months later...

I was tuned in and got a kick out of that. I appreciate it. 

 

I'm happy that this can pick back up. I just turned in a few samples and intend to post the results when I get them back. I'm hopeful that by establishing a more complete profile of a particular chemotype that more information will be revealed. 

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Abstract  

Persistent pains associated with inflammatory and neuropathic states are prevalent and debilitating diseases, which still remain without a safe and adequate treatment. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological properties and is considered to have anti-inflammatory action. Here, we assessed the effects and the underlying mechanisms of action of euphol in preventing inflammatory and neuropathic pain. Oral treatment with euphol (30 and 100 mg/kg) reduced carrageenan-induced mechanical hyperalgesia. Likewise, euphol given through the spinal and intracerebroventricular routes prevented mechanical hyperalgesia induced by carrageenan. Euphol consistently blocked the mechanical hyperalgesia induced by complete Freund's adjuvant, keratinocyte-derived chemokine, interleukin-1β, interleukin-6 and tumor necrosis factor-alpha associated with the suppression of myeloperoxidase activity in the mouse paw. Oral treatment with euphol was also effective in preventing the mechanical nociceptive response induced by ligation of the sciatic nerve and also significantly reduced the levels and mRNA of cytokines/chemokines in both paw and spinal cord tissues following i.pl. injection of complete Freund's adjuvant. In addition, the pre-treatment with either CB1R or CB2R antagonists, as well as the knockdown gene of the CB1R and CB2R, significantly reversed the antinociceptive effect of euphol. Interestingly, even in higher doses, euphol did not cause any relevant action in the central nervous system. Considering that few drugs are currently available for the treatment of chronic pain states, the present results provided evidence that euphol constitutes a promising molecule for the management of inflammatory and neuropathic pain states.

Highlights

► Euphol displays pronounced anti-inflammatory and antinociceptive properties. ► Euphol inhibit the activation and/or release of inflammatory mediators. ► Euphol has systemic, spinal and supraspinal antinociception actions. ► Euphol interact with cannabinoid system.

Euphol, a tetracyclic triterpene produces antinociceptive effects in inflammatory and neuropathic pain: The involvement of cannabinoid system
   
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i never thought "tumor necrosis" would be such a great term, but it is.

i want to put that on a tshirt or bumper sticker.

 

terpenes huh? 

 

Conifer wood, balm trees, citrus fruits, coriander, eucalyptus, lavender, lemon
grass, lilies, carnation, caraway, peppermint species, roses, rosemary, sage, thyme,
violet and many other plants or parts of those (roots, rhizomes, stems, leaves, blos-
soms, fruits, seed) are well known to smell pleasantly, to taste spicy, or to exhibit
specific pharmacological activities.

 

The biological and ecochemical functions of terpenes have not yet been fully inves-
tigated. Many plants produce volatile terpenes in order to attract specific insects for
pollination or otherwise to expel certain animals using these plants as food. Less
volatile but strongly bitter-tasting or toxic terpenes also protect some plants from
being eaten by animals (antifeedants). Last, but not least, terpenes play an impor-
tant role as signal compounds and growth regulators (phytohormones) of plants, as
shown by preliminary investigations.

 

terpenes and herbal medicine?

 

http://umm.edu/health/medical/altmed/herb/lemon-balm

 

Lemon balm (Melissa officinalis), a member of the mint family, is considered a calming herb. It was used as far back as the Middle Ages to reduce stress and anxiety, promote sleep, improve appetite, and ease pain and discomfort from indigestion (including gas and bloating, as well as colic). Even before the Middle Ages, lemon balm was steeped in wine to lift the spirits, help heal wounds, and treat venomous insect bites and stings. Today, lemon balm is often combined with other calming, soothing herbs, such as valerian, chamomile, and hops, to help promote relaxation. It is also used in creams to treat cold sores (oral herpes).

 

 

For example, in one study of people with minor sleep problems, 81% of those who took an herbal combination of valerian and lemon balm reported sleeping much better than those who took placebo.

 

In another double blind, placebo controlled study, 18 healthy volunteers received 2 separate single doses of a standardized lemon balm extract (300 mg and 600 mg) or placebo for 7 days. The 600 mg dose of lemon balm increased mood and significantly increased calmness and alertness.

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what terpenes are in lemon balm?

 

http://cdn.naturaldispensary.com/downloads/A_Research_Review_of_Lemon_Balm.pdf

 

ACTIVE CONSTITUENTS
Active constituents include, phenolic acids and flavonoids, including up to 6% rosmarinic acid,
coumaric, caffeic, luteolin-7-glucoside, rhamnazin, campesterol, catechins, chlorogenic-acid,
protocatechuic acid, 10-(Alpha)-cadinol, copaene, beta-sitosterol, succinic acid, thymol,
hexanoic acid, stachyose, and trans-ocimene.

Rosmarinic acid is a caffeic acid derivative found in several Labaitae family members and
credited with both antioxidant and immune modulating effects, as well euthyroid effects.
Rosmarinic acid works by several mechanisms of action to normalize hyperthyroidism, including
binding to thyroid stimulating autoantibodies and preventing them from binding to TSH
receptors.
The essential oil (0.02–0.37%) content is composed of monoterpenes, sesquiterpenes and
terpenoid components including citral, citronellal, eugenol, geraniol, nerol, linalool, farnesyl
acetate, humulene, ursolic, and pomolic acids.

Research on Melissa officinalis has shown that growing and harvesting techniques influence the
essential oil content of the plant and that the top third of the leafy plant has the highest
amount of volatile oil.

linalool, eugenol and humulene are found in cannabis and lemon balm.

 

wow, just searcing for individual terpenes finds lots of studies on each one as being anti-tumor anti-cancer anti-alzhiemers.

this is incredible the amount of info out there. just have to put it all together?

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Thanks for the info about lemon balm!

 

There's a book on terpenes that I've yet to get, but is used as one of Russo's primary references in 'The Entourage Effect':

 

http://www.amazon.com/Handbook-Essential-Oils-Technology-Applications/dp/1420063154%3FSubscriptionId%3DAKIAILSHYYTFIVPWUY6Q%26tag%3Dduckduckgo-z-20%26linkCode%3Dxm2%26camp%3D2025%26creative%3D165953%26creativeASIN%3D1420063154

 

There are a ton of variables to consider, and it's safe to say that there's a wide range of quality, in regards to essential oils. I've been using Aromatics International. They provide GC/MS on each batch of oil so you know exactly what you're getting. On their website you can search for oils by entering in the chemical constituents that you're looking for, which is really convenient.

 

http://www.aromaticsinternational.com/index.php?route=product/component 

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  • 4 weeks later...

I'd refrain from using a microwave oven when processing cannabis, its extracts, or distillations. A microwave will change the compounds from one of the highest vibrational frequencies, to one of the lowest. The energy emitted inside will change the nutritional value of water.The same results with food, but that's another thread. Health results from eating "dead" or low frequency items are no secret. 

 

This is the most comprehensive terpenoid thread I've seen, thank you for the share.

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I was trying to get that guy to give me a deal. I would have needed a bunch of extra ice cones to make it at all practical. He didn't budge. But there has been analysis of comparisons between microwave and normal steam distillation. 

 

Rather than trying to do a number of multiple runs with the microwave setup, I've opted to go with a traditional stainless steel setup instead.

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Oh it's on now! I'm stoked that this research can finally continue! I'm going to go about these one at a time. I've got quite a bit of homework to do.

 

Hindu Kush Review:

 

Method of consumption being reviewed: Smoked

 

The period of the day you use this strain the most: Day or Evening

 

List of some of the effects that I feel feel describe this strain:

 

Initially Anxious into Soothing/Relaxed, Well Rounded, Creative, Disorientating, Slightly Energetic, Euphoric, Focused, Happy, Hungry, Positive, Relief,  Talkative, Tingly, Therapeutic, Uplifted

 

List of aromas that I associate with this strain:

 

Earthy, Flowery, Skunky, Spicy/Herbal

 

The first cannabinoid and terpene profile I'd like to go over is a hindu kush chemotype. When we previously had this cut tested I was highly disappointed. This has been a long standing all around favorite of mine for a few years. The previous cannabinoid profile was limited. I think to CBD, THC, and CBN, and the acidic forms of those. The hk tested around 17% total, mainly delta9. Other strains tested at the same time that are vastly different, some of which also considered weaker, tested in this area as well. There was no way for me to account for any variance in effect. I viewed that type of testing as lacking any real meaning. I attributed the variance to the terpenes, but was it?

 

hindu_cannabinoid_chart.jpg

 

med_gallery_34991_1162_11484.jpeg
 
hindu_kush_terpene_content.jpg
 
med_gallery_34991_1162_51274.jpeg

 

As you can see it turns out that this HK is high in CBG. 

 

Non-psychotropic cannabinoid obtained in 1964 by Gaoni and
Mechoulam when they separated a hexane extract of hashish
on Florisil. It exerts anti-proliferative and antibacterial activity.
It is a potent TRPM8 antagonist [14], a TRPV1, TRPA1 and
cannabinoid agonist, and an anandamide reuptake inhibitor in
the low micromolar range [11,14].

 

CBG could be considered for clinical experimentation in IBD patients.

 

I'm gonna post this so I can view these tables more easily.

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CBG has a number of interesting characteristics:

 

It's a anandamide uptake inhibitor, so it can raise anandamide levels. 

 

It's a TRPA1 and TRPV1 agonist, and TRPM8 antagonist. I want to say that TRPV1 is the target or capsaicin (topicals). I'm not familiar with the other ones, but it looks like they might have similar functions.

 

The CB1, CB2, TRPA1, TRPV1 activation might suggest that this chemotype is good for topical applications. However, TRPV1 activation might also suggest that it's not good for a person who has seizures.

 

The implications in terms of CBG and IBD also seems to suggest that this would be a good chemtype for that treatment.

 

I haven't gotten a chance to go over the terpenes yet.

 

First up

alpha-terpenine (main terpene constituent in a number of 'mostly sativa strains')

 

α-Terpinene and its oxidation products were identified in all of the tea tree oil samples. Thus, from a technical perspective, α-terpinene is a true antioxidant since it autoxidizes rapidly compared with many other compounds, preventing these from degradation. However, as it easily autoxidizes to form allergens, its suitability can be questioned when used in products for topical applications, e.g., in tea tree oil but also in cosmetics and skin care products.

 

Maybe I spoke too soon on the topical front.

 

But
 

It is one of the components responsible for the antioxidant activity of tea tree oil. α-Terpinene is structurally similar to other monoterpenes, e.g., limonene, known to autoxidize on air exposure and form allergenic compounds.

 

So all monoterpenes do this? hmm That'll be something to dig a little deeper into later.

 

Looks like it may have some antibacterial properties, and antifungal.

 

Beta-caryophyllene is next highest. You're all familiar with that one. Full CB2 agonist, good for topicals (direct activation of CB2). I've been using balsam copaiba for my source. 

 

If all monoterpenes (many in cannabis) autoxidize on air to form allergenic compounds, this might be back in the running for topical applications.

 

Alpha and beta-pinene are next up. Alpha-pinene is another one I sourced (white pine), but never used it in the topicals because the fragrance of white pine is overbearing.

 

According to Russo alpha-pinene is anti-inflammatory, a bronchodilator (good for asthma), and and AChE inhibitor (aids memory).

 

I'll post more on them later.

 

Next up is beta-myrcene (high in some types of hops), which is believed to contribute to the 'couch lock' effect. According to Russo it's a sedative, a muscle relaxant, and a hypnotic. Its believed to work synergistically with THC to elicit analgesic effects. It also is believed to aid CBG in blocking hepatic carcinogens (cancer implication).

 

This post is getting long and I've lost one tonight as is. I think I'll post this and continue.

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I missed beta-ocimene. Never heard of it. It looks like it's compared to b-myrcene in a number of articles. 

 

This is describing possible pharmacological mechanism for beta-ocimene and beta-myrcene:

 

An important question in olfaction is for which odorants receptor neurones have evolved. In the present study, olfactory receptor neurones on the antennae of the tobacco budworm moth Heliothis virescens were screened for sensitivity to naturally occurring plant-produced volatiles by the use of gas chromatography linked to electrophysiology. Volatiles of host as well as non-host plants collected by headspace techniques were used for stimulating the neurones, sequentially via two columns, one polar and one nonpolar installed in parallel in the gas chromatograph. Three types of neurones presented in this paper responded to one, two or three compounds for which the retention times were determined in both column types. The chemical structures of the active components were determined on the basis of mass spectrometry linked to gas chromatography, indicating E-β-ocimene and β-myrcene as stimulants for neurone type 1, E,E-α-farnesene for neurone type 2 and homo-farnesene for neurone type 3. Re-testing authentic materials verified the identifications for the type 1 neurones. The results demonstrate a high specificity for the three types of neurones by strong responses to one or two structurally similar compounds out of hundreds present in a large variety of plants. The study exemplifies plant odour detection by narrowly tuned receptor neurones in a polyphagous moth species.

 

http://link.springer.com/article/10.1007/s003590000136

 

 

neurone type 1

 

Neurons in the nervous system exhibit an outstanding variety of morphological and physiological properties. However, close to threshold, this remarkable richness may be grouped succinctly into two basic types of excitability, often referred to as type I and type II. The dynamical traits of these two neuron types have been extensively characterized. It would be interesting, however, to understand the information-processing consequences of their dynamical properties. To that end, here we determine the differences between the stimulus features inducing firing in type I and in type II neurons. We work both with realistic conductance-based models and minimal normal forms. We conclude that type I neurons fire in response to scale-free depolarizing stimuli. Type II neurons, instead, are most efficiently driven by input stimuli containing both depolarizing and hyperpolarizing phases, with significant power in the frequency band corresponding to the intrinsic frequencies of the cell.

 

http://arxiv.org/abs/0801.3963

 

That's gonna take some time to decipher..

 

Here's something random but interesting (alpha-pinene/mango scent):
 

The value of spices is primarily based on their aroma
and flavor characteristics (Bandyopadhyay, 1993). The
popular name of C. amada in south Asian countries,
mango ginger, is due to its particular aroma of raw
mango. Various attempts have been made to identify
the volatile aroma components responsible for this characteristic
mango aroma. Gholap and Bandyopadhyay
(1984) tentatively identified three terpene hydrocarbons,
i.e. α-pinene, car-3-ene and cis-ocimene, and suggested
that the latter two compounds contribute to the characteristic
mango flavor, whereas α-pinene contributes to
the aroma. However, in another study, cis- and transhydroocimene,
ocimene and myrcene were determined
to be the major character-affecting compounds of C.
amada volatile oils, indicating that the aroma of mango

ginger comprises a mixture of character-affecting compounds
found in both raw mango and turmeric (Rao et al.,
1989). The chemical compounds responsible for the mango
aroma of mango ginger should be studied further.

 

http://onlinelibrary.wiley.com/doi/10.1002/ptr.2137/abstract

 

Next up is alpha-humulene. Looks like there's some anti-inflammatory characteristics. Anti-tumor activity.

 

We evaluated the effects of balsam fir oil and α-humulene on the cellular glutathione (GSH) content and on the production of reactive oxygen species (ROS). Balsam fir oil and α-humulene induced a dose- and time-dependent decrease in cellular GSH content and an increase in ROS production. These results suggest that GSH depletion and ROS production may be implicated in the cytotoxicity of α-humulene and balsam fir oil.

 

 

beta-caryophyllene potentiates the anticancer activity of alpha-humulene.

 

β-caryophyllene is a sesquiterpene widely distributed in essential oils of various plants. Several biological activities are attributed to β-caryophyllene, such as anti-inflammatory, antibiotic, antioxidant, anticarcinogenic and local anaesthetic activities. In this work, the potentiating effect of β-caryophyllene on the anticancer activity of α-humulene, isocaryophyllene and paclitaxel against MCF-7, DLD-1 and L-929 human tumour cell lines was evaluated. A non-cytotoxic concentration of β-caryophyllene significantly increased the anticancer activity of α-humulene and isocaryophyllene on MCF-7 cells: α-humulene or isocaryophyllene alone (32 μg mL−1) inhibited cell growth by about 50% and 69%, respectively, compared with 75% and 90% when combined with 10 μg mL−1 β-caryophyllene. Moreover, β-caryophyllene potentiated the anticancer activity of paclitaxel on MCF-7, DLD-1 and L-929 cell lines. The highest potentiating effect was obtained in DLD-1 cells treated with paclitaxel combined with 10 μg mL−1 β-caryophyllene, which increased the paclitaxel activity about 10-fold. The intracellular accumulation of paclitaxel-oregon green was evaluated in combination with concentrations of β-caryophyllene ranging from 2.5 to 40 μg mL−1. β-Caryophyllene (10 μg mL−1) significantly increased the intracellular accumulation of paclitaxel-oregon green (about 64% over controls). Moreover, β-caryophyllene induced intracellular accumulation of calcein but not verapamil, an inhibitor of P-glycoprotein and multidrug resistance related protein transporters, suggesting that β-caryophyllene promotes drug accumulation by a different mechanism of action. These results suggest that β-caryophyllene facilitates the passage of paclitaxel through the membrane and thus potentiates its anticancer activity.

 

http://onlinelibrary.wiley.com/doi/10.1211/jpp.59.12.0005/abstract

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CONCLUSIONS

The differential cytotoxicity of C. sylvestris against tumoral cells A-549, HeLa and HT-29 shows that the use of the plant against different types of cancers might present positive results, since the leaves essential oil presented low cytotoxicity against non tumoral cells (Vero cells and mice macrophages). Moreover, the tests realized using two sesquiterpens found in guaçatonga (β-caryophyllene and α-humulene) presented similar results to the ones verified for the plant essential oil, indicating that they might be responsible for the cytotoxic action verified. In fact, the sum up of β-caryophyllene and α-humulene fractions of C. sylvestris represents a high percentage of the essential oil total composition used in this study (around 22.8%), and it was possible to suppose that the cytotoxic effects against tumoral cells (A-549, HeLa and HT-29) observed in the action of C. sylvestris essential oil can be related to the presence of both substances on this plant's leaves. These sesquiterpens have already been described as cytotoxic components of other plant oils (Sibanda et al., 2004; Sylvestre et al., 2005; Hou et al., 2006; Sylvestre et al., 2006).

 

These results are important for the characterization of the cytotoxicity action of C. sylvestris, since most of the investigations related to the cytotoxic activity of guaçatonga are mainly associated to diterpens (casearins) isolated from alcoholic extracts of the plant (Morita et al., 1991; Carvalho et al., 1998; Beutler et al., 2000; Orberlies et al., 2002; Maistro et al., 2004; Mosaddick et al., 2004). The selective action of β-caryophyllene and α-humulene in the C. sylvestris essential oil against tumor cells associated to casearins isolated from alcoholic extracts might help in the explanation of the anticancer activity popularly associated to the plant.

 

However, in opposition to the studies of Basile et al., (1990) which verified that the C. sylvestris leaves alcoholic extracts caused low acute toxicity, we concluded that the use of solutions containing high content of essential oil from leaves of guaçatonga must be carried out carefully. In fact, from Table 3, it was possible to verify that all the tested erythrocytes were, in some degree, sensitive to the essential oil of C. sylvestris. The human and bovine erythrocytes were the most sensitive to the essential oil, indicating that, for the therapeutic use of the plant, it is necessary to observe the quantity of oil that reaches the bloodstream. Since the erythrocytes have presented the same sensitivity to both β-caryophyllene and α-humulene, we can attribute to the sesquiterpens, at least in part, the toxic effects observed.

 

http://www.scielo.br/scielo.php?pid=S0044-59672008000100012&script=sci_arttext

 

So beta-caryophyllene and alpha-humulene might both be good for cancer treatment. At least in small amounts. I wasn't aware of that about the potential hazards with beta-caryophyllene. Good to know. It's a cannabinoid found in dietary sources. I wonder how this dosing might correlate to levels achieved from consuming these compounds. The quantities in cannabis are very minimal and not likely of concern. But beta-caryophyllene could potentially be if a person was taking supplements of it. I'm surprised I haven't seen anything about that previously. I'll look into it some more later.  

 

Nobody wants to give up the goods on Sabinene. I can find articles in searches, but can't read them for free. Looks like possibly anti-inflammatory properties.

 

Then there's some limonene

 

According to Russo:

 

possible cannabinoid agonist

immune potentiator

antidepressant

antimutagenic

 

 

As we gain insight into the plant, I believe we'll gain insight into how best to use it. I think I'm gonna figure out a way right now.

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The entourage effect seems to be the phenomenon responsible for the fact that many experienced medical cannabis users can tell whether a given strain will work for them based on scent alone.

 

Many terpenes can readily cross the blood-brain barrier and elicit a response through olfactory senses. We know what smells "nice" to us, but I'd wager that beyond any subjective interpretation along those lines, or an association from past experience, would be as far as that could take you. I struggle to see how smelling the terpenes will provide insight into the cannabinoids. I like the smell of cannatonic #4. I can't place it. I think it smells like a power skunk I had back in the day. I enjoyed the power skunk, the cannatonic 4 isn't really my thing.  

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Many terpenes can readily cross the blood-brain barrier and elicit a response through olfactory senses. We know what smells "nice" to us, but I'd wager that beyond any subjective interpretation along those lines, or an association from past experience, would be as far as that could take you. I struggle to see how smelling the terpenes will provide insight into the cannabinoids. I like the smell of cannatonic #4. I can't place it. I think it smells like a power skunk I had back in the day. I enjoyed the power skunk, the cannatonic 4 isn't really my thing.

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