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


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(Update 3/12/14)

 

Many of you are well aware of the importance of the role of terpenes, flavonoids,  and nonpsychoactive cannabinoids in terms of the effects and therapeutic benefits of cannabis. Strains with similar content and ratios of THC/CBD/CBN can have wildly different effects. Why is that? Well, some of the main constituents in cannabis are the nonpsychoactive cannabinoids, as well as terpenes and flavonoids. As researchers like Russo have so plainly pointed out (and a history of anecdotal experiences confirms), they matter. Understanding what the constituents in cannabis are, and what they do is a missing piece to the puzzle. I believe that we can begin to investigate this piece to the puzzle in MI with the tools currently at our disposal. We need to start talking more directly about terpene profiles in addition to cannabinoid profiles. This will help in terms of therapeutic value, breeding, and doing away with the inadequate indica/sativa nomenclature. It seems like there's much to be learned and gained from a better understanding terpene and cannabinoid ratios.      

 

While I applaud the efforts of the testing services in MI, I hope that in time we see their services evolve into offering more complete cannabis profiles. (edit: Labs in MI are now quantifying terpenes!) This is currently a hurdle in my own attempts at maximizing therapeutic and breeding potential. Thankfully, we have access to a body of knowledge in relation to terpenes. I'd like to discuss some of that knowledge in this thread.

 

When I started this thread we didn't have the ability to quantify terpenes in MI. That is no longer the case. That means rather than the 'entourage effect' being an aspect of cannabis that is easy to identify subjectively, while being a sort of unattainable novelty in terms of systematic application, that systematic application is now attainable. The time to begin to apply knowledge about the differing effects of varying cannabinoid and terpene ratios is at hand. Any patient in MI so inclined is now able to take this craft from one based on feel and art, to one that couples that art to science, or at least quasi-science.


 

This thread is dedicated to that pursuit. I'm posting cannabinoid and terpene ratios of strains I'm working with. I'm also including reviews on these strains from my patients in regards to the effectiveness of each strain with their treatment. I'd like for us to begin to examine the specific differences and commonalities between strains. Talk about what implications the particular cannabinoids and terpenes have in relation to therapeutic value. Determine the differences between sativa and indica hybrids, and what exactly what it is about that one strain that you seem to like so much.


 

A little further down this page there's a list of the terpene content from 17 different 'mostly sativa' and 'mostly indica' strains. With just those 17 examples patterns already begin to emerge that might allow us to begin to understand the difference between these varieties. We can also quantify over twice as many as they were in that study. Instead of having to discuss strains in terms of indica or sativa, wouldn't it be great to be able to further differentiate by asking is that sativa high in α-terpinolene, α-pinene, or elemene (and knowing the difference)? What's the myrcene content in that indica? Etc..


 

Some other areas of interest include levying more control via the growing process to impact the content and ratios of desired cannabinoids. Procuring CBC and CBG rich extracts. Most importantly learning how each specific cannabinoid and terpene might relate to cannabis based therapies, and how to predict to increase the efficacy of our treatments through this understanding.


 

I'm posting profiles for all of the strains that I can, but my efforts alone might not be enough. What I'd like to see is other patients and caregivers beginning to share profiles and reviews for their strains as well. If you're not comfortable posting it, you can send it to me privately, and I'll post it for you. I'm also willing to analyze your profile in the same way I'm attempting to do with mine. If we can identify patterns with the 17 profiles listed below, what patterns might we identify with 100 profiles?

 

There will be some discussion about local and systemic administration of terpenes found in a number of natural forms including essential oils in this thread. Attempts will be made to understand the potential dangers and benefits of these compounds (alone and in concert). It would not surprise me if many of these compounds have their own adverse effects, and may even be carcinogens at higher levels. Any information in this thread, particularly from me, is not to be taken as professional advice. You should always consult with your physician before incorporating any new variable to your health and wellness regiment.

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Here are some important papers covering the 'entourage effect':

Russo EB (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, 163: 1344-1364.

 

Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, a-pinene, linalool, b-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human diets that have been designated Generally Recognized as Safe by the US Food and Drug Administration and other regulatory agencies. Terpenoids are quite potent, and affect animal and even human behaviour when inhaled from ambient air at serum levels in the single digits. They display unique therapeutic effects that may contribute meaningfully to the entourage effects of cannabis-based medicinal extracts. Particular focus will be placed on phytocannabinoid-terpenoid interactions that could produce synergy with respect to treatment of pain, inflammation, depression, anxiety, addiction, epilepsy, cancer, fungal and bacterial infections (including methicillin-resistant Staphylococcus aureus).

 

(These descriptions below are from Taming THC, but I wasn't able to post that many quotes.)
 

THC is a partial agonist at CB1 and cannabinoid receptor 2 (CB2) analogous to AEA, and underlying many of its activities as a psychoactive agent, analgesic, muscle relaxant and antispasmodic.  Additionally, it is a bronchodilator, neuroprotective antioxidant, antipruritic agent in cholestatic jaundice and has 20 times the antiinflammatory power of aspirin and twice that of hydrocortisone.

CBD has proven extremely versatile pharmacologically displaying the unusual ability to antagonize CB1 at a low nM level in the presence of THC, despite having little binding affinity, and supporting its modulatory effect on THC-associated adverse events such as anxiety, tachycardia, hunger and sedation in rats and humans.  CBD is an analgesic, is a neuroprotective antioxidant more potent than ascorbate or tocopherol, without COX inhibition, acts as a TRPV1 agonist analogous to capsaicin but without noxious effect, while also inhibiting uptake of AEA and weakly inhibiting its hydrolysis.  CBD is an antagonist on GPR55, and also on GPR18, possibly supporting a therapeutic role in disorders of cell migration, notably endometriosis.  CBD is anticonvulsant, anti-nausea, cytotoxic in breast cancer and many other cell lines while being cyto-preservative for normal cells, antagonizes tumour necrosis factor-alpha (TNF-a) in a rodent model of rheumatoid arthritis, enhances adenosine receptor A2A signalling via inhibition of an adenosine transporter, and prevents prion accumulation and neuronal toxicity.  A CBD extract showed greater anti-hyperalgesia over pure compound in a rat model with decreased allodynia, improved thermal perception and nerve growth factor levels and decreased oxidative damage.  CBD also displayed powerful activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 0.5 & 2 mg/mL-1.  In 2005, it was demonstrated that CBD has agonistic activity at 5-hydroxytryptamine (5-HT)1A at 16 mM, and that despite the high concentration, may underlie its anti-anxiety activity, reduction of stroke risk, anti-nausea effects and ability to affect improvement in cognition in a mouse model of hepatic encephalopathy.  A recent study has demonstrated that CBD 30 mg/kg-1 i.p. reduced immobility time in the forced swim test compared to imipramine, an effect blocked by pre-treatment with the 5-HT1A antagonist WAY100635, supporting a prospective role for CBD as an antidepressant.  CBD also inhibits synthesis of lipids in sebocytes, and produces apoptosis at higher doses in a model of acne (vide infra).  One example of CBD antagonism to THC would be the recent observation of lymphopenia in rats (CBD 5 mg/kg-1) mediated by possible CB2 inverse agonism, an effect not reported in humans even at doses of pure CBD up to 800 mg, possibly due to marked interspecies differences in CB2 sequences and signal transduction.  CBD proved to be a critical factor in the ability of nabiximols oromucosal extract in successfully treating intractable cancer pain patients unresponsive to opioids (30% reduction in pain from baseline), as a high-THC extract devoid of CBD failed to distinguish from placebo.  This may represent true synergy if the THC & CBD combination were shown to provide a larger effect than a summation of those from the compounds separately.


CBC has anti-inflammatory and analgesic activity, its ability to reduce THC intoxication in mice, antibiotic and antifungal effects, and observed cytotoxicity in cancer cell lines. A CBC-extract displayed pronounced antidepressant effect in rodent models. Additionally, CBC was comparable to mustard oil in stimulating TRPA1- mediated Ca++ in human embryonic kidney 293 cells (50 & 60 nM). CBC recently proved to be a strong AEA uptake inhibitor. CBC production is normally maximal, earlier in the plant's life cycle. An innovative technique employing cold water extraction of immature leaf matter from selectively bred cannabis chemotypes yields a high-CBC & enriched trichome preparations.


CBG, the parent phytocannabinoid compound, has a relatively weak partial agonistic effect at CB1 (Ki 440 nM) and CB2 (Ki 337 nM). Older work supports gamma aminobutyric acid (GABA) uptake inhibition greater than THC or CBD that could suggest muscle relaxant properties. Analgesic and anti-erythemic effects and the ability to block lipooxygenase were said to surpass those of THC. CBG demonstrated modest antifungal effects. More recently, it proved to be an effective cytotoxic in high dosage on human epithelioid carcinoma, is the next most effective phytocannabinoid against breast cancer after CBD, is an antidepressant in the rodent tail suspension model and is a mildly anti-hypertensive agent. Additionally, CBG inhibits keratinocyte proliferation suggesting utility in psoriasis, it is a relatively potent TRPM8 antagonist for possible application in prostate cancer and detrusor over-activity and bladder pain. It is a strong AEA uptake inhibitor and a powerful agent against MRSA. Finally, CBG behaves as a potent a-2 adrenorecep-tor agonist, supporting analgesic effects previously noted, and moderate 5-HT1A antagonist suggesting antidepressant properties. Normally, CBG appears as a relatively low concentration intermediate in the plant, but recent breeding work has yielded cannabis chemotypes lacking in downstream enzymes that express 100% of their phytocannabinoid content as CBG.


THCV is a propyl analogue of THC, and can modulate intoxication of the latter, displaying 25% of its potency in early testing. A recrudescence of interest accrues to this compound, which is a CB1 antagonist at lower doses, but is a CB1 agonist at higher doses. THCV produces weight loss, decreased body fat and serum leptin concentrations with increased energy expenditure in obese mice. THCV also demonstrates prominent anticonvulsant properties in rodent cerebellum and pyriform cortex. THCV appears as a fractional component of many southern African cannabis chemotypes, although plants highly predominant in this agent have been produced. THCV recently demonstrated a CB2-based ability to suppress carageenan-induced hyperalgesia and inflammation, and both phases of formalin-induced pain behaviour via CB1 and CB2 in mice.


CBDV, the propyl analogue of CBD, was first isolated in 1969, but formerly received little investigation. Pure CBDV inhibits diacylglycerol lipase [50% inhibitory concentration (IC50) 16.6 mM] and might decrease activity of its product, the endocannabinoid, 2-AG. It is also anticonvulsant in rodent hippocampal brain slices, comparable to phenobarbitone and felbamate.


CBN is a non-enzymatic oxidative by-product of THC, more prominent in aged cannabis samples. It has a lower affinity for CB1 (Ki 211.2 nM) and CB2 (Ki 126.4 nM); and was judged inactive when tested alone in human volunteers, but produced greater sedation combined with THC. CBN demonstrated anticonvulsant, anti-inflammatory (Evans, 1991) and potent effects against MRSA (MIC 1 mg & mL-1). CBN is a TRPV2 (high threshold thermosensor) agonist (EC 77.7 mM) of possible interest in treatment of burns. Like CBG, it inhibits keratinocyte proliferation, independently of cannabinoid receptor effects. CBN stimulates the recruitment of quiescent mesenchymal stem cells in marrow (10 mM), suggesting promotion of bone formation (Scutt and Williamson, 2007) and inhibits breast cancer resistance protein, albeit at a very high concentration (IC50 145 mM).


Terpenoids are pharmacologically versatile: they are lipophilic, interact with cell membranes, neuronal and muscle ion channels, neurotransmitter receptors, G-protein coupled (odorant) receptors, second messenger systems and enzymes (Bowles, 2003; Buchbauer, 2010). All the terpenoids discussed herein are Generally Recognized as Safe, as attested by the US Food and Drug Administration as food additives, or by the Food and Extract Manufacturers Association and other world regulatory bodies. Germane is the observation (Adams and Taylor, 2010)(p. 193), ‘With a high degree of confidence one may presume that EOs derived from food are likely to be safe’.

 

 

Are cannabis terpenoids actually relevant to the effects of cannabis? Terpenoid components in concentrations above 0.05% are considered pharmacological interest (Adams and Taylor, 2010).



D-limonene, common to the lemon and other citrus EOs, is the second most widely distributed terpenoid in nature, and is the precursor to other monoterpenoids through species-specific synthetic schemes.  Unfortunately, these pathways have not yet been investigated in cannabis. The ubiquity of limonene serves, perhaps, as a demonstration of convergent evolution that supports an important ecological role for this monoterpene.  Studies with varying methodology and dosing in citrus oils in mice suggest it to be a powerful anxiolytic agent, with one EO increasing serotonin in the prefrontal cortex, and dopamine (DA) in hippocampus mediated via 5-HT1A. Compelling confirmatory evidence in humans was provided in a clinical study, in which hospitalized depressed patients were exposed to citrus fragrance in ambient air, with subsequent normalization of Hamilton Depression Scores, successful discontinuation of antidepressant medication in 9/12 patients and serum evidence of immune stimulation (CD4/8 ratio normalization). Limonene also produces apoptosis of breast cancer cells, and was employed at high doses in Phase II RCTs. Subsequent investigation in cancer treatment has centred on its immediate hepatic metabolite, perillic acid, which demonstrates anti-stress effects in rat brain. A patent has been submitted, claiming that limonene effectively treats gastro-oesophageal reflux. Citrus EOs containing limonene proved effective against dermatophytes, and citrus EOs with terpenoid profiles resembling those in cannabis demonstrated strong radical scavenging properties. As noted above,limonene is highly bioavailable, and rapidly metabolized, but with indications of accumulation and retention in adipose tissues (e.g. brain). It is highly non-toxic (estimated human lethal dose 0.5-5 g/kg-1) and non-sensitizing.


Myrcene is another common monoterpenoid in cannabis with myriad activities: diminishing inflammation via prostaglandin E-2 (PGE-2), and blocking hepatic carcinogenesis by aflatoxin. Interestingly, myrcene is analgesic in mice, but this action can be blocked by naloxone, perhaps via the a-2 adrenoreceptor. It is nonmutagenic in the Ames test. Myrcene is a recognized sedative as part of hops preparations (Humulus lupulus), employed to aid sleep in Germany. Furthermore, myrcene acted as a muscle relaxant in mice, and potentiated barbiturate sleep time at high doses. Together, these data would support the hypothesis that myrcene is a prominent sedative terpenoid in cannabis, and combined with THC, may produce the 'couch-lock' phenomenon of certain chemotypes that is alternatively decried or appreciated by recreational cannabis consumers.


a-Pinene is a bicyclic monoterpene, and the most widely encountered terpenoid in nature. It appears in conifers and innumerable plant EOs, with an insect-repellent role. It is anti-inflammatory via PGE-1, and is a bronchodilator in humans at low exposure levels. Pinene is a major component of Sideritis spp. and Salvia spp. EOs, both with prominent activity against MRSA (vide infra). Beyond this, it seems to be a broadspectrum antibiotic. a-Pinene forms the biosynthetic base for CB2 ligands, such as HU-308. Perhaps most compelling, however, is its activity as an acetylcholinesterase inhibitor aiding memory, with an observed IC50 of 0.44 mM. This feature could counteract short-termnmemory deficits induced by THC intoxication (vide infra).


D-Linalool is a monoterpenoid alcohol, common to lavender (Lavandula angustifolia), whose psychotropic anxiolytic activity has been reviewed in detail. Interestingly, linalyl acetate, the other primary terpenoid in lavender, hydrolyses to linalool in gastric secretions.  Linalool proved sedating to mouse activity on inhalation. In traditional aromatherapy, linalool is the likely suspect in the remarkable therapeutic capabilities of lavender EO to alleviate skin burns without scarring.  Pertinent to this, the local anaesthetic effects of linalool are equal to those of procaine and menthol.  Another explanation would be its ability to produce hot-plate analgesia in mice that was reduced by administration of an adenosine A2A antagonist.  It is also anti-nociceptive at high doses in mice via ionotropic glutamate receptors.  Linalool demonstrated anticonvulsant and antiglutamatergic activity, and reduced seizures as part of Ocimum basilicum EO after exposure to pentylenetetrazole, picrotoxin and strychnine.  Furthermore, linalool decreased K+-stimulated glutamate release and uptake in mouse synaptosomes.  These effects were summarized; Overall, it seems reasonable to argue that the modulation of glutamate and GABA neurotransmitter systems are likely to be the critical mechanism responsible for the sedative, anxiolytic and anticonvulsant properties of linalool and EOs containing linalool in significant proportions.  Linalool also proved to be a powerful anti-leishmanial agent, and as a presumed lavender EO component, decreased morphine opioid usage after inhalation versus placebo in gastric banding in morbidly obese surgical patients.


b-Caryophyllene is generally the most common sesquiterpenoid encountered in cannabis, wherein its evolutionary function may be due to its ability to attract insect predatory green lacewings, while simultaneously inhibiting insect herbivory.  It is frequently the predominant terpenoid overall in cannabis extracts, particularly if they have been processed under heat for decarboxylation.  Caryophyllene is common to black pepper (Piper nigrum) and Copaiba balsam (Copaifera officinalis).  It is anti-inflammatory via PGE-1, comparable in potency to the toxic phenylbutazone, and an EO containing it was on par with etodolac and indomethacin.  In contrast to the latter agents, however, caryophyllene was a gastric cytoprotective, much as had been claimed in the past in treating duodenal ulcers in the UK with cannabis extract.  Caryophyllene may have contributed to antimalarial effects as an EO component.  Perhaps the greatest revelation regarding caryophyllene has been its demonstration as a selective full agonist at CB2 (100 nM), the first proven phytocannabinoid beyond the cannabis genus.  Subsequent work has demonstrated that this dietary component produced antiinflammatory analgesic activity at the lowest dose of 5 mg/kg-1 in wild-type, but not CB2 knockout mice.  Given the lack of attributed psychoactivity of CB2 agonists, caryophyllene offers great promise as a therapeutic compound, whether systemically, or in dermatological applications such as contact dermatitis. Sensitization reactions are quite rare, and probably due to oxidized product.


Nerolidol is a sesquiterpene alcohol with sedative properties, present as a low-level component in orange and other citrus peels. It diminished experimentally induced formation of colon adenomas in rats. It was an effective agent for enhancing skin penetration of 5-fluorouracil. This could be a helpful property in treating fungal growth, where it is also an inhibitor. It seems to have anti-protozoal parasite control benefits, as a potent antimalarial and anti-leishmanial agent. Nerolidol is nontoxic and non-sensitizing.


Caryophyllene oxide is a sesquiterpenoid oxide common to lemon balm (Melissa officinalis), and to the eucalyptus, Melaleuca stypheloides, whose EO contains 43.8%. In the plant, it serves as an insecticidal/anti-feedant and as broad-spectrum antifungal in plant deficiencies. Analogously, the latter properties may prove therapeutic, as caryophyllene oxide demonstrated antifungal efficacy in a model of clinical onychomycosis comparable to ciclopiroxalamine and sulconazole, with an 8% concentration affecting eradication in 15 days. Caryophyllene oxide is non-toxic and non-sensitizing.  This agent also demonstrates anti-platelet aggregation properties in vitro. Caryophyllene oxide has the distinction of being the component responsible for cannabis identification by drug-sniffing dogs.


Phytol is a diterpene, present in cannabis extracts, as a breakdown product of chlorophyll and tocopherol. Phytol prevented vitamin A-induced teratogenesis by inhibiting conversion of retinol to a harmful metabolite, all-trans-retinoic acid. Phytol increased GABA expression via inhibition of succinic semialdehyde dehydrogenase, one of its degradative enzymes. Thus, the presence of phytol could account for the alleged relaxing effect of wild lettuce (Lactuca sativa), or green tea (Camellia sinensis), despite the latters caffeine content.


Gardner F (2011). Terpenoids, 'minor' cannabinoids contribute to 'entourage effect' of Cannabis-based medicines. O'Shaugnessy's, Autumn 2011. (Short easy to read article.)


Russo EB and McPartland JM (2003). Cannabis is more than simply & Delta-9-tetrahydrocannabinol. Psychopharmacology, 165: 431-432.

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Though I didn't have much luck with this approach, you might be able to identify terpenes in strains through the association of aromas from other sources. Here's a chart that I found:

 

Basic Terpene Chart

 

Similiar to basil, lemon grass, or peppermint, cannabis emanates its own unique fragrance, consisting of hydrocarbons found in the plant's resin. These hydrocarbons are a group of compounds known as terpenoids. They offer a unique and efficient way of anticipating how a strain will affect a patient, because of how they intereact with active cannabinoids like tetrahyrocannabinol (THC). Use this Basic Terpenoid Chart to familiarize yourself with the fragrances of those terpenes most often found in medicinal cannabis.

 

Myrcene: citrus, clove, earthy, fruity, green, vegetative, mango

 

Limonene: citrus (orange, tangerine, lemon, and grapefruit), Rosemary, juniper, peppermint

 

Caryophyllene: spicy, sweet, woody, clove, camphor, pepper

 

Pinene: alpha: pine needles, rosemary, beta: dill, parsley, rosemary, basil, yarrow, rose, hops

 

Terpineol: floral; lilac, citrus, apple/ orange blossoms, lime

 

Borneol: menthol, camphor, pine, woody

 

Delta 3-Carene: sweet, pine, cedar, woodsy, rosemary

 

Linalool: floral (spring flowers), lilly, citrus and candied spice.

 

Pulegone: mint, camphor, rosemary, candied

 

Eucalyptol (aka 1.8 Cineole): spicy; camphor, refreshing, rosemary

 

Farnesol: floral; muguet, lilly, tuberose, rose, musk, acacia, lemon grass;delicate, mild, sweet

 

Nerolidol: woody (like fresh tree bark), floral, green, waxy, citrus

 

Humulene vietnamese coriander, hops, woody, clove

 

In the field of aromatherapy, terpenoids have been administered for their therapeutic value. Recent findings have concluded that terpenoids actually change how the body metabolizes cannabinoids like tetrahydrocannabinol (THC). Understanding how to properly identify a terpenoid will enhance your knowledge of cannabis, and enable you to select a strain based on what it is intended to treat.

 

From:

http://www.istraingu...m/terpenoid.php

 

 

 

terpenes2.jpg

 

http://www.medicaljane.com/2013/04/13/terpenes-terpenoids-what-are-they-what-do-they-do/

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Here's an awesome thesis on terpenes (partially available):

 

Terpenes in Medicine

https://openaccess.leidenuniv.nl/bitstream/handle/1887/20608/04.pdf?sequence=10

 

Other potential protein targets of terpenoids are the transient receptor potential channels (TRP) also known as vanilloid or capsaicin receptors... The TRP vanilloid-3 (TRPV3) is known to be involved in skin inflammation and peripheral nerve injuries. Camphor and cineol not only activate the TRPV3 but desensitize the receptor after long term exposure which may explain their mechanism as topical analgesics (Sherkheli et al., 2009). Sesquiterpene dialdehyes which are pungent ingredients in certain spices also activate vanilloid receptors (Szallasi et al., 1998)... Interestingly the dietary sesquiterpenoid, β-caryophyllene is a potent and selective CB2 receptor agonist with anti-inflammatory properties. Many herbs and spices including cannabis, cinnamon, and black pepper contain significant amounts of β-caryophyllene (Gertsch, 2008).

 

 

Monoterpenoids such as limonene and its main metabolite in humans, perillyl alcohol exhibit antitumor activities (Figure 9). Other monoterpenoid alcohols such as geraniol, linalool, carveol prevent tumor formation in chemically induced tumor animal models. Many essential oils have also been tested for cytotoxic and antitumor properties (Buchbauer, 2010).


 

The antimicrobial effects of many spices containing terpenoids suggest that cultural preferences for certain flavors may have developed throughout history due to health promoting or food preservation benefits (Goff and Klee, 2006).


 

In contrast with other senses, olfactory information can bypass the thalamus and directly link with areas of the brain involved in emotion and memory such as the amygdala, frontal cortex, hypothalamus, and hippocampus (Kandal et al., 2000). Furthermore due to their lipophilic nature terpenoids are able to pass the blood brain barrier (BBB) and interact directly with the brain. Both mechanisms are important because odorous terpenoids can have a direct pharmacological action in the brain, such as interaction with a neural receptor, and a psychological component through the olfactory system (Heuberger, 2010).


 

Thesis outline and goals

 

Throughout this discussion a number of issues become apparent with regards to complications in the development of terpenoids and plants containing them as drugs. One major issue is that plants and products derived from them such as essential oils or extracts are often of variable or unknown chemical composition. Another issue concerns administration forms of volatile terpenoids. Often protocols for administering essential oils vary between studies and controlled dosing is difficult. Finally for many terpenoids the mechanisms of action and structure activity relationships are still unknown. Therefore the major goals of this thesis are:

1. Investigate vaporization as an administration form for volatile terpenoids in various medicinal plants.
2. Determine if plants can be standardized to produce reproducible levels of active components in order to improve clinical research.
3. Isolate and study the biological activity of medically interesting sesquiterpenoids and diterpenoids.

 

In chapter 2 a device designed to administer plant volatile compounds called a vaporizer was investigated. Some common terpenoid producing plants with medicinal properties were selected and tested in the device. The essential oil content and terpenoid content of the vapor was analyzed with GC and GC-MS.

 

In chapter 3, cannabis was used as a model plant to test the vaporizer in more detail, compare it with cannabis smoke, and test whether any components in the smoke or vapor altered the CB1 binding of THC in-vitro. In order to determine if plants producing terpenoids can be standardized for their chemical content cannabis was again chosen as a model plant.

 

In chapter 4 a number of cannabis varieties grown in multiple batches under the same environmental conditions were analyzed with GC-FID and GC-MS. Multivariant data analysis was used to chemically classify the varieties. The reproducibility of the chemical profiles was determined.

 

 

 

The second chapter of Terpenes in Medicine begins to discuss and explore reproducible administration of essential oils with a vaporizer. This takes eating a mango to the next level. It's potentially a way to increase therapeutic value and potentially gain the ability to shift the effects of cannabis that is otherwise lacking in terpenes that are beneficial to you.

 

Potential therapeutic effects of inhaled essential oils include antimicrobial, antiviral, anti-carcinogenic, sedative, analgesic, anxiolytic, and anti-inflammatory effects (Edris, 2007).

 

  Although some clinical trials have been performed on essential oils administered in an aromatherapy setting, most have weak experimental designs and thus the effectiveness of such approaches is questionable (Yim et al., 2009; Cooke and Ernst, 2000).

 

Some variation between the constituents in the essential oil and the vapor was noted, but it was determined that a Volcano was capable of reproducibility.

 

 

Chapter 3 of Terpenes in Medicine:

 

This is an interesting study performed by Bedrocan (the only licensed provider of medicinal cannabis in the Netherlands). This study is almost worthy of it's own thread. They evaluate vapor vs smoked cannabis, and investigate the effects that terpenes have on CB1 binding. They don't recognize any difference in CB1 binding with the addition of terpenes, and they suggest a mechanism other than CB1 agonism for their effects.  

 

The information in regards to the differences between the constituents in smoke versus vapor is interesting. It seems to suggest that individuals that seek to increase their intake of CBN may be better off smoking rather than vaping. 

 

(Bedrocan study: Cannabinoid receptor 1 binding activity and quantitative analysis of Cannabis sativa L. smoke and vapor)

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Chapter 8 of Terpenes in Medicine:
 

This question of multiple active ingredients, which is a common question when studying a herbal drug, can only truly be answered with properly designed clinical trials in humans using standardized and chemically defined plant sources.

 

Indeed the results demonstrated that cannabis varieties can be distinguished based on cannabinoid and terpenoid profiles. Interestingly cannabis varieties with  similar levels of Δ9-THC could be differentiated based on mono and sesquiterpenoid content.

 

Overall the results from chapters 3 and 4 demonstrate that it is possible to standardize a plant producing volatile terpenoids and its administration form. Although cannabis was chosen as a model example due to its complex chemical profile and ongoing clinical research it is in theory possible to take such an approach with any plant or herbal product as long ascertain criteria can be met.

 

If cannabis is used as an example the following clinical protocol could be envisioned; as treatments two or more cannabis varieties with unique chemical profiles, the isolated essential oil of each variety, equivalent doses of Δ9-THC as a positive control, and a negative control with no drugs. Administered to humans with a relevant illness one could then conclusively address the question over whether herbal cannabis is more or less therapeutically effective compared with pure Δ9-THC for that particular illness.

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Here's our starting point. This is a study (and graphic from that study) on the terpene profiles for some 'mostly indica' and 'mostly sativa' strains. As you can see, with just sixteen profiles patterns in regards to differences between the two already begin to emerge. Over time as we continue to analyze these strains we will be able to do away with the sativa/indica nomenclature altogether.

 

Terpenes are strongly inherited and little influenced by environmental factors and,
therefore, have been widely used as biochemical marker in chemosystematic studies to
characterize plant species, provenances, clones and hybrids.

 

CONCLUSIONS


The main differences between terpene profiles of the evaluated strains belonging
to the two principal biotypes were that ‘mostly indica’ strains were characterized by
dominancy of β-myrcene, present in high relative contents, with limonene or α-pinene as
second most abundant terpenoid, while ‘mostly sativa’ strains were characterized by more
complex terpene profiles, with some strains having α-terpinolene or α-pinene as dominant
terpenoid, and some strains having β-myrcene as dominant terpenoid with α-terpinolene
or trans-β-ocimene as second most abundant terpenoid.


This wide variability in terpene composition can provide a potential tool for the
characterization of Cannabis biotypes, and warrant further researches in order to evaluate
the drug’s medical value and, at the same time, to select less susceptible chemotypes to
the attack of herbivores and diseases. More detailed studies on the variability in
monoterpenes and sesquiterpenes are needed.
Breeding for specific terpenoids in plants is
a fascinating research topic; in fact, the various biological activities of these compounds
make the analysis of terpenoids a valuable tool for improving a considerable number of
traits in pharmaceutical and industrial cultivars of Cannabis.


Terpenoids analysis, combined with cannabinoids and flavonoids analyses, are
essential for the metabolic fingerprinting of pharmaceutical cultivars. Pharmaceutical
cultivars of the two principal biotypes may exhibit distinctive medicinal properties due to
significant differences in relative contents of terpenoids
, thus the synergy between the
various secondary metabolites must be investigated in deeper details in the future in order
to better elucidate the phytocomplex of Cannabis and to allow selection of chemotypes
with specific medical effects.

 

Variations in Terpene Profiles of Different Strains of Cannabis sativa L.

 

I can't link it directly, but if you search Google Scholar you can get a free pdf.

 

 

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This patent from 2013 titled "Phytocannabinoids in the treatment of cancer" provides some insights into terpenes (and a number of cannabinoids). They did testing with synthesized cannabinoids, as well as extracted (with terpenes present) and showed that the extract was more effective in most of the tests. They also mention adding terpenes from other botanical sources. 

 

This is a good example of the ways that we can learn to increase the efficacy of cannabinoid based treatments. 

 

This patent and others from this year mention and provide percentages of the terpenes in their "inventions". If you're interested in finding terpenes for your condition you might want to look at the most recent patents.

 

They seem to focus on monoterpenes and sesquiterpenes.

 

This one used myrcene as the principle monoterpene and pinene as the secondary.

 

They also used caryophyllene as the primary sesquiterpene and humulene as the secondary.

Edited by in vivo
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There are a number of breeders that are beginning to focus more on cannabinoid and terpene ratios.

 

GHS has some info on their terpene and cannabinoid profiles here:

 

http://www.greenhouseseeds.nl/shop/strains-terpenes-profiles.html

 

I also recommend searching through cannabis testing sites, some allow you to view the results from the strains they analyze.

 

There are some here in MI, I also like to use:

 

http://analytical360.com

 

You can search for strains by name and view cannabinoid and terpene profiles.

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What does a terpene profile look like?  About to search Google for an answer.  Any additional input is appreciated.

 

edit:  should have kept reading here.  Got too excited.  I've been working on Nerolidol and didn't even know it.

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Smoke the weed, it'll help you from catching malaria.  Great, now I'm really high and I'm in the jungle.  That's going in the new movie.

 

That's really interesting, also, I see some differences.  For example, I have a super heavy nerolidol strain with limonene recessed into the genetics, and it's anything but sedative, it's a super soaring sativa.  So, while nerolidol might be sedative, with genetic expression and recombination through selective breeding, I wonder how this all applies, and I'm wondering on what genetic level that switches are being recombined and switched on and off.  Maybe it's something from the lemon that's making it soar?

 

edit:  Thanks for these posts, it's awesome.

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Thanks for joining the conversation.

 

The terpene profile would be a scientifically measured amount of the terpenes in a sample of cannabis, or essential oil for that matter. There are likely too many to test for them all, but if we could start with some of the ones listed by Russo, that would be a great start. This will help to eliminate much of the confusion and guesswork that is sure to be associated with subjective identification methods like the charts listed here.   

 

I don't believe that consuming cannabis will prevent or put malaria into remission. Best to stay out of the jungle. 

 

I'm not sure that I follow your last question. It sounds to me as if you've identified nerolidol in one of your strains via sense of smell, and possibly one of the parents is believed to have been high in limonene. Is that correct?    

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Phytocannabinoids

 

THC (Δ-9-tetrahydrocannabinol)

Boiling point: 157° C / 314.6° Fahrenheit

Properties: Euphoriant, Analgesic, Anti Inflammatory, Antioxidant, Antiemetic

CBD (cannabidiol)

Boiling point: 160-180°C / 320-356° Fahrenheit

Properties: Anxiolytic, Analgesic, Antipsychotic, Anti Inflammatory, Antioxidant, Antispasmodic

CBN (Cannabinol)

Boiling point: 185°C / 365° Fahrenheit

Properties: Oxidation, breakdown, product, Sedative, Antibiotic

CBC (cannabichromene)

Boiling point: 220° / 428° Fahrenheit

Properties: Anti Inflammatory, Antibiotic, Antifungal

Δ-8-THC (Δ-8-tetrahydrocannabinol)

Boiling point: 175-178°C / 347-352.4° Fahrenheit

Properties: Resembles Δ-9-THC, Less psychoactive, More stable Antiemetic

THCV (Tetrahydrocannabivarin)

Boiling point: < 220°C / <428° Fahrenheit

Properties: Analgesic, Euphoriant

Terpenoid Essential Oil Components of Cannabis

β-Myrcene

Boiling point: 166-168°C / 330.8-334.4° Fahrenheit

Properties: Analgesic. Anti Inflammatory, Antibiotic, Antimutagenic

β-Caryophyllene

Boiling point: 119°C / 246.2° Fahrenheit

Properties: Anti Inflammatory, Cytoprotective (gastric mucosa), Antimalarial

d-Limonene

Boiling point: 177°C / 350.6° Fahrenheit

Properties: Cannabinoid agonist?, Immune potentiator, Antidepressant, Antimutagenic

Linalool

Boiling point: 198°C / 388.4° Fahrenheit

Properties: Sedative, Antidepressant, Anxiolytic, Immune potentiator

Pulegone

Boiling point: 224°C / 435.2° Fahrenheit

Properties: Memory booster?, AChE inhibitor, Sedative, Antipyretic

1,8-Cineole (Eucalyptol)

Boiling point: 176°C / 348.8° Fahrenheit

Properties: AChE inhibitor, Increases cerebral, blood flow, Stimulant, Antibiotic, Antiviral, Anti Inflammatory, Antinociceptive

α-Pinene

Boiling point: 156°C / 312.8° Fahrenheit

Properties: Anti Inflammatory, Bronchodilator, Stimulant, Antibiotic, Antineoplastic, AChE inhibitor

α-Terpineol

Boiling point: 217-218°C / 422.6-424.4° Fahrenheit

Properties: Sedative, Antibiotic, AChE inhibitor, Antioxidant, Antimalarial

Terpineol-4-ol

Boiling point: 209°C / 408.2° Fahrenheit

Properties: AChE inhibitor. Antibiotic

p-Cymene

Boiling point: 177°C / 350.6° Fahrenheit

Properties: Antibiotic, Anticandidal, AChE inhibitor

Borneol

Boiling point: 210°C / 410° Fahrenheit

Properties: Antibiotic

Δ-3-Carene

Boiling point: 168*C / 334.4° Fahrenheit

Properties: Anti Inflammatory

Flavonoid and Phytosterol Components of Cannabis

Apigenin

Boiling point: 178°C / 352.4° Fahrenheit

Properties: Anxiolytic, Anti Inflammatory, Estrogenic

Quercetin

Boiling point: 250°C / 482° Fahrenheit

Properties: Antioxidant, Antimutagenic, Antiviral, Antineoplastic

Cannflavin A

Boiling point: 182°C / 359.6° Fahrenheit

Properties: COX inhibitor, LO inhibitor

β-Sitosterol

Boiling point: 134°C / 273.2° Fahrenheit

Properties: Anti Inflammatory, 5-α-reductase, inhibitor

 

 

Cannabis and cannabis extracts: greater than the sum of their parts? Edited by in vivo
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Olive oil

Hemp seed oil

Osha Root (Furanocoumarins ?%, mucilage ?%)

tincture of myrrh (curzerene 27%, furanoeudsmadiene 35%, lindeatrene 10%)

oil of peppermint (menthone 22%, menthol 37%)

oil of clary sage (linalyl acytate 54%, linalool 26%)

oil of oregano (carvacrol 63%)

 

This is PB's recipe. I looked up the constituents, and added them, to identify what it is that's being used beyond the common names of the essential oil. The numbers posted are from GC/MS run on the products from the supplier that I'm using.

 

I'm not familiar with the constituents in the Osha root, oregano, or myrrh.

 

The clary sage seems like a decent source of linalool (skin penetrant, local anesthetic), but I'm not sure about the acetate. 

 

The peppermint will likely cool and sooth the skin creating a pleasant sensation.

 

Another option for topical oils might be:

Magnolia officinalis root bark extract - honokoi 88% , magnolol 11% (CB1 & CB2 agonist with CB2 selectivity)

Balsam Copaiba - b-caryophyllene 55%, caryophyllene oxide 35% (CB2 agonist, anti-inflammatory, anti fungal)

Thyme ct linalool - linalool 39%, b-myrcene 9% (skin penetrant, analgesic, local anesthetic)

Juniper Berry - a-Pinene 43%, b-myrcene 12% ( anti-inflammatory, analgesic, antibiotic)

Ho Wood - linalool 98% (local anesthetic, skin penetrant)

 

The percentages and constituents can vary a great deal between batches of essential oils. They also have shelf lives of 2-5 years depending on the oil. If you're going to buy essential oils, I recommend getting them from a source that provides GC/MS, and the distilled date, on all of their products.

 

What are some of your favorite essential oils, and why?

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  • 2 weeks later...

While reading about the myrcene content in various types of hops, I've realized that the reason I get more intoxicated from pale ales is likely due to the fact that the hops that go into them are especially high in myrcene.

 

For those of you that have seen the GW Pharmaceuticals thread (grow section) you're likely aware of my interest in using steam distillation to capture the terpenes from plants. I've stumbled across an interesting microwave distillation setup that seems like an easy way for any grower to capture the essential oil/terpenes from their plants.

 

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Terpenes are easily destroyed and most processes for extraction or concentration destroy them.

 

Cooking hash oil kills em quick.  Cold extractions are better.

 

 Here are a few links I have about extractions and such:

 

Extraction Technology for Medicinal and Aromatic Plants  <--- This is like a 101 course on it.

 

Terpenes in Cannabis - Green House Seeds Profiles

 

And here is a compilation post I made several years ago:

 

 

Well, as a matter of default from discussing the benefits of organics i decided to talk about a crucial yet commonly overlooked component of cannabis, Flavonoids.

To get me started i want to catch you up to the basic discussion that started this next addition to my blog series in case you missed it.

It started with the release of the NFA's report stating that chemical grown produce was just as good as organically grown produce. Well, once i actually read the HIGHLY biased report, even by their calculations and conclusion, organics were alot better. As much as 38% better in the production of Flavonoids than in chemically grown produce. So i decided to move a few things over from that thread and add a little more letting people know what are Flavonoids and why they are important in Cannabis.

This was the news article i seen rebutting the rosie picture they tried to put out about the study....

A cancerous conspiracy to poison your faith in organic food

http://www.dailymail.co.uk/debate/artic ... N-A-canc...

Yet even in the context of the latest report from the FSA, the spin does not match the reality. For, contrary to all the hype this week, the Agency's own published research shows that organic foods are clearly far better for the consumer even just in nutritional terms.

According to the FSA's findings, organic vegetables contain 53.6 per cent more betacarotene - which helps combat cancer and heart disease - than non-organic ones.

Similarly, organic food has 11.3 per cent more zinc, 38.4 per cent more flavonoids and 12.7 per cent more proteins.

In addition, an in-depth study by Newcastle University, far deeper than the one conducted by the FSA, has shown that organic produce contains 40 per cent more antioxidants than non-organic foods, research the FSA appears to have overlooked. But the concentration solely on nutrition is to play into the hands of the anti-organic, pro-industrial lobby. As most of the British public understands, but the FSA fails to acknowledge, the benefits of organic food go far beyond this narrow point.

The flavonoid production statistic stood out at me when i read it (kinda like it does now) because i know how important Flavonoids are.
-----------------------

 


SO....

Here we go...


Basic Definition:

Flavonoids (or bioflavonoids) are a class of plant secondary metabolites. According to the IUPAC nomenclature, they can be classified into:

flavonoids, derived from 2-phenylchromen-4-one (2-phenyl-1,4-benzopyrone) structure

isoflavonoids, derived from 3-phenylchromen-4-one (3-phenyl-1,4-benzopyrone) structure

neoflavonoids, derived from 4-phenylcoumarine (4-phenyl-1,2-benzopyrone) structure.

Flavonoids are most commonly known for their antioxidant activity. Flavonoids are also commonly referred to as bioflavonoids in the media – the terms are largely equivalent and interchangeable, for most flavonoids are biological in origin. Flavonoids are "the most common group of polyphenolic compounds in the human diet and are found ubiquitously in plants".

Biosynthesis
Flavonoids are synthesized by the phenylpropanoid metabolic pathway in which the amino acid phenylalanine is used to produce 4-coumaroyl-CoA. This can be combined with malonyl-CoA to yield the true backbone of flavonoids, a group of compounds called chalcones, which contain two phenyl rings (see polyphenols). Conjugate ring-closure of chalcones results in the familiar form of flavonoids, the three-ringed structure of a flavone. The metabolic pathway continues through a series of enzymatic modifications to yield flavanones → dihydroflavonols → anthocyanins. Along this pathway, many products can be formed, including the flavonols, flavan-3-ols, proanthocyanidins (tannins) and a host of other various polyphenolics.

Biological effects
Flavonoids are widely distributed in plants fulfilling many functions including producing yellow or red/blue pigmentation in flowers and protection from attack by microbes and insects. The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active plant compounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Flavonoids have been referred to as "nature's biological response modifiers" because of strong experimental evidence of their inherent ability to modify the body's reaction to allergens, viruses, and carcinogens. They show anti-allergic, anti-inflammatory , anti-microbial and anti-cancer activity.

Consumers and food manufacturers have become interested in flavonoids for their medicinal properties, especially their potential role in the prevention of cancers and cardiovascular disease. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins.

Cancer
The process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention. Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion." UCLA cancer researchers have found that study participants who ate foods containing certain flavonoids seemed to be protected from developing lung cancer. Dr. Zuo-Feng Zhang, of the UCLA's Jonsson Cancer Center and a professor of public health and epidemiology at the UCLA School of Public Health said the flavonoids that appeared to be the most protective included catechin, found in strawberries and green and black teas; kaempferol, found in brussel sprouts and apples; and quercetin, found in beans, onions and apples.

Their research also indicated that only small amounts of flavonoids are necessary to see these medical benefits. Taking large dietary supplements provides no extra benefit and may pose some risks.

Diarrhea
A study done at Children's Hospital & Research Center Oakland, in collaboration with scientists at Heinrich Heine University in Germany, has shown that epicatechin, quercetin and luteolin can inhibit the development of fluids that result in diarrhea by targeting the intestinal cystic fibrosis transmembrane conductance regulator Cl– transport inhibiting cAMP-stimulated Cl– secretion in the intestine.

Important flavonoids

Quercetin is a flavonoid and, to be more specific, a flavonol. It is the aglycone form of a number of other flavonoid glycosides, such as rutin and quercitrin, found in citrus fruit, buckwheat and onions. Quercetin forms the glycosides quercitrin and rutin together with rhamnose and rutinose, respectively. It may also help to prevent some types of cancer, however currently there is more research needed in this area.

Epicatechin (EC)Epicatechin improves blood flow and thus seems good for cardiac health. Cocoa, the major ingredient of dark chocolate, contains relatively high amounts of epicatechin and has been found to have nearly twice the antioxidant content of red wine and up to three times that of green tea in in-vitro tests. But in the test outlined above it now appears the beneficial antioxidant effects are minimal as the antioxidants are rapidly excreted from the body.

Proanthocyanidins extracts demonstrate a wide range of pharmacological activity. Their effects include increasing intracellular vitamin C levels, decreasing capillary permeability and fragility, scavenging oxidants and free radicals, and inhibiting destruction of collagen, the most abundant protein in the body.

_____________________________________

From Cannabis and Cannabinoids

Flavonoids are aromatic, polycyclic phenols. About 20 are found in Cannabis, as free flavonoids and conjugated glycosides. Apigenin, kaempferol, luteolin, orientin, and quercetin exist in many plants; other flavonoids are unique to cannabis, such as cannflavins. Flavonoids, like terpenoids, exert a wide range of biological effects. Some are liophilic, permeate membranes, and cross the BBB(blood brain barrier). Flavonoids are volatile, can be collected by steam distillation, and apparently retain pharmocological activity in cannabis smoke.

Flavonoids in cannabis inhibit protaglandin E production, more than cannabinoids AND terpenoids. Anti-inflammatory activity is also exhibited by flavonoid related phenols in cannabis(e.g., Eugenol), and marijuana smoke(e.g., p-vinylphenol). Apigenin inhibits tumor necrosis factor(TNF)-induced inflammation.
Quercetin and other flavonoids are potent atin-oxidants; some flavonoids show greater activity than ascorbic acid and a-tocopherol.

Certain flavonoids also exhibit SERT activity and others are MAO inhibitors.

___________________________________________

Flavonoids are 3-ring phenolic compounds consisting of a double ring attached by a single bond to a third ring. In leaves they block far ultraviolet (UV) light (which is highly destructive to nucleic acids and proteins), while selectively admitting light of blue and red wavelengths which is crucial for photosynthesis. Flavonoids include water soluble pigments (such as anthocyanins) that are found in cell vacuoles. [Note: Carotenoids are fat soluble pigments found in plastids.] You have probably observed water soluble anthocyanins if you have cut open a fresh head of red cabbage. [Note: The nitrogen-containing, water soluble pigment in beets is not a flavonoid, but a different type of chemical called a betacyanin or betalain, with a complex chemical structure similar to an alkaloid. Betacyanins also produce the reddish color of flowers such as Bougainvillea.] Water soluble flavonoids (mostly anthocyanins) are responsible for the colors of many flowers and can range from red to blue, depending on the pH of the watery sap in the vacuoles. The common garden shrub called hydrangea (Hydrangea macrophylla ) produces showy clusters of white, pink, red or blue flowers depending on the pH of the soil.

________________________________________

Cannabis produces approximately 20 flavonoid type compounds and up to 1% of the leaf mass is attributed to their content. Flavonoids may modulate the pharmacokinetic activity of THC via a mechanism that is shared by CBD, which is the inhibition of P450 2A11 and P450 3A4 enzymes. P450 suppressing compounds serve as chemoprotective agents by shielding healthy cells from the activation of benzo{a}pyrene and aflatoxin B1, which are two procarconogens potentially located in cannabis smoke.

________________________________________

Quercetin, a flavonoid in cannabis, is able to act as an antioxidant and its importance as in inhibitor of nuclear transcription factor kappa(NF-kB) has been of interest for over a decade. Downstream productss of NF-kB activation include inflammatory cytokines important for leukocyte activation and recruitment, tumour necrosis fact(TNF), nitric oxide synthase(NOS), and thus regulation of vascular tone, cell adhesion molecule expression involved in inflammatory responses, and viral activation such as in HIV. Free radicals activate NF-kB and quercetin has been shown to arrest the formation of this molecule by blocking the protein kinase C (PKC) induced phosphorylation if an inhibitory sub-unti of NF-kB termed IkB. The results of this are that quercetin may actively inhibit carcinogenisis and stimulation/development of some inflammatory diseases.

Cannflavin A is a prenylated flavone which so far is unique to cannabis. This compound has been shown to be an inhibitor of PGE2 in human rheumatoid synovial cells with an IC value 30 times more potent than aspirin in the same model. It has also been shown to exhibit cyclooygenase(COX) and lipoxygenase(LO) more potently than THC.
__________________________________________

Flavonoids have antioxidant activity. Flavonoids are becoming very popular because they have many health promoting effects. Some of the activities attributed to flavonoids include: anti-allergic, anti-cancer, antioxidant, anti-inflammatory and anti-viral. The flavonoids quercetin is known for its ability to relieve hay fever, eszema, sinusitis and asthma.
Epidemiological studies have illustrated that heart diseases are inversely related to flavonoid intake. Studies have shown that flavonoids prevent the oxidation of low-density lipoprotein thereby reducing the risk for the development of atherosclerosis.
The contribution of flavonoids to the total antioxidant activity of components in food can be very high because daily intake can vary between 50 to 500 mg.
Red wine contains high levels of flavonoids, mainly quercetin and rutin. The high intake of red wine (and flavonoids) by the French might explain why they suffer less from coronary heart disease then other Europeans, although their consumption of cholesterol rich foods is higher (French paradox). Many studies have confirmed that one or two (joints) glasses of red wine daily can protect against heart disease. icon_e_smile.gif

__________________________________________

What is are the functions of flavonoids?

Protection of cell structures

Most flavonoids function in the human body as antioxidants. In this capacity, they help neutralize overly reactive oxygen-containing molecules and prevent these overly reactive molecules from damaging parts of cells. Particularly in oriental medicine, plant flavonoids have been used for centuries in conjunction with their antioxidant, protective properties. Scultellaria root, cornus fruit, licorice, and green tea are examples of flavonoid-containing foods widely used in oriental medicine. While flavonoids may exert their cell structure protection through a variety of mechanisms, one of their potent effects may be through their ability to increase levels of glutathione, a powerful antioxidant, as suggested by various research studies.

Vitamin C support

The relationship between flavonoids and vitamin C was actually discovered by mistake. Dr. Albert Szent-Gyorgyi, the Nobel Prize winning researcher who discovered flavonoids, was attempting to make a preparation of vitamin C for one of his patients with blood vessel problems. The preparation he gave the patient was not 100% pure - it contained other substances along with the vitamin C. It worked amazingly well.

Later, when Dr. Szent-Gyorgyi purchased a pure solution of vitamin C, he found it was not nearly so effective with his patient. He suspected flavonoids as the magic addition to vitamin C in his first impure preparation. Present-day research has clearly documented the synergistic (mutually beneficial) relationship between flavonoids and vitamin C. Each substance improves the antioxidant activity of the other, and many of the vitamin-related functions of vitamin C also appear to require the presence of flavonoids.

Inflammation control

Inflammation - the body's natural response to danger or damage - must always be carefully regulated to prevent overactivation of the immune system and unwanted immune response. Many types of cells involved with the immune system - including T cells, B cells, NK cells, mast cells, and neutrophils - have been shown to alter their behavior in the presence of flavonoids. Prevention of excessive inflammation appear to be a key role played by many different chemical categories of flavonoids.

Antibiotic activity

In some cases, flavonoids can act directly as antibiotics by disrupting the function of microorganisms like viruses or bacteria. The antiviral function of flavonoids has been demonstrated with the HIV virus, and also with HSV-1, a herpes simplex virus.

What are deficiency symptoms for flavonoids?

Excessive bruisability, nose bleeds, swelling after injury, and hemorrhoids can be indicators of flavonoid deficiency. Generally weakened immune function, as evidenced by frequent colds or infections, can also be a sign of inadequate dietary intake of flavonoids.

Toxicity Symptoms

What are toxicity symptoms for flavonoids?

Even in very high amounts (for example, 140 grams per day), flavonoids do not appear to cause unwanted side effects. Even when raised to the level of 10% of total caloric intake, flavonoid supplementation has been shown non-toxic. Studies during pregnancy have also failed to show problems with high-level intake of flavonoids.

Impact of Cooking, Storage and Processing
(I just want to say that it is water and vapor soluble,so this is obvious)

How do cooking, storage, or processing affect flavonoids?

Heat, degree of acidity (pH), and degree of processing can have a dramatic impact on the flavonoid content of food. For example, in fresh cut spinach, boiling extracts 50% of the total flavonoid content.

With onions (a less delicate food), boiling still removes about 30% of the flavonoids (and specifically, a group of flavonoids called the quercitin glycosides). Overcooking of vegetables has particularly problematic effects on this category of nutrients.

Factors that Affect Function

What factors might contribute to a deficiency of flavonoids?

Poor intake of fruits and vegetables - or routine intake of high-processed fruits and vegetables - are common contributing factors to flavonoid deficiency. It is difficult to overemphasize the impact of processing and a non-whole foods diet on flavonoid intake. If the pulpy, fibrous parts of fruits are eliminated from the juice, and the vibrant natural colors of canned vegetables are lost during repeated heating, risk of flavonoid deficiency is greatly increased.

Drug-Nutrient Interactions

What medications affect flavonoids?

The impact of prescription medicines on flavonoid status is not well studied. However, in an interesting twist when looking from the other direction at the impact of flavonoids on drug status, researchers have discovered that a flavonoid in grapefruit juice called naringin can increase the absorption of certain heart-related drugs (including nifedipine, felodipine and verapamil), as well as the antihistamine terfenadine.

Nutrient Interactions

How do other nutrients interact with flavonoids?

Present-day research has clearly documented the synergistic (mutually beneficial) relationship between flavonoids and vitamin C. Each substance improves the antioxidant activity of the other, and many of the vitamin-related functions of vitamin C also appear to require the presence of flavonoids.

Health Conditions

What health conditions require special emphasis on flavonoids?

Flavonoids may play a role in the prevention and/or treatment of the following health conditions:

Allergy
Asthma
Atopic dermatitis
Candida infection
Cataracts
Diabetes
Gout
Hemorrhoids
Macular degeneration
Migraine
Periodontal disease
Stomach ulcer
Varicose veins
Form in Dietary Supplements
 

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