Derbybud
Well-Known Member
It's the rest of the world that is f- upped
SweetSue's Class Notes
- Thread starter SweetSue
- Start date
- Thread starter
- #782
From “Natural Compounds in Cancer Therapy” by John Boik
Limonene
Primary constituent of orange oil
- Midseason seeet orange oil may contain 80-96% limonene
- analysis of some commercial orange oils revealed zero % limonene
U of Wisconsin studies found limonene to be effective in hindering (in rodents) cancer of
- stomach
- lung
- skin
- liver
Oral admin. of limonene (10% of diet) for three weeks caused tumor regression in 89% Of treated rats with chemically-induced breast cancer
- min dose of 7.5% of diet was necessary for complete regression
- both small and large tumors
- majority of tumor regressions were complete
- regression remained complete as long as limonene was continued
- little or no toxicity observed
The human equivalent dose would be about 91 grams a day
- may induce adverse effects in humans
At lower doses (less than 1% of diet) limonene inhibited breast cancer dev. by a variety of carcinogens (in rats)
Anti-carcinogenic effects of monoterpenes likely due to their ability to stimulate drug metabolism in they liver
- effectively detoxifies carcinogens
“Monoterpenes induce a wider spectrum of detoxification enzymes than does they classic enzyme-producer, phenobarbital. “ - John Boik
Limonene is rapidly metabolized in vivid to active terpene derivatives
- within one hour of oral admin. more than 80% of limonene is metabolized to derivatives
In humans, 40% of oral limonene is metabolized to perillic acid
- appears to be main anti-tumor effects
Synergistic interactions may be necessary to produce desired anti-tumor effects
Tumor cells may develop resistance to monoterpenes
- may be helpful to combine with agents that reduce multi drug resistance
Tumor regression due to monoterpenes is reversible
- continued treatment may be necessary
Limonene
Primary constituent of orange oil
- Midseason seeet orange oil may contain 80-96% limonene
- analysis of some commercial orange oils revealed zero % limonene
U of Wisconsin studies found limonene to be effective in hindering (in rodents) cancer of
- stomach
- lung
- skin
- liver
Oral admin. of limonene (10% of diet) for three weeks caused tumor regression in 89% Of treated rats with chemically-induced breast cancer
- min dose of 7.5% of diet was necessary for complete regression
- both small and large tumors
- majority of tumor regressions were complete
- regression remained complete as long as limonene was continued
- little or no toxicity observed
The human equivalent dose would be about 91 grams a day
- may induce adverse effects in humans
At lower doses (less than 1% of diet) limonene inhibited breast cancer dev. by a variety of carcinogens (in rats)
Anti-carcinogenic effects of monoterpenes likely due to their ability to stimulate drug metabolism in they liver
- effectively detoxifies carcinogens
“Monoterpenes induce a wider spectrum of detoxification enzymes than does they classic enzyme-producer, phenobarbital. “ - John Boik
Limonene is rapidly metabolized in vivid to active terpene derivatives
- within one hour of oral admin. more than 80% of limonene is metabolized to derivatives
In humans, 40% of oral limonene is metabolized to perillic acid
- appears to be main anti-tumor effects
Synergistic interactions may be necessary to produce desired anti-tumor effects
Tumor cells may develop resistance to monoterpenes
- may be helpful to combine with agents that reduce multi drug resistance
Tumor regression due to monoterpenes is reversible
- continued treatment may be necessary
- Thread starter
- #783
Chaos interferes with cognitive coherence. This first video explains what the body does in chaos and how easily the body responds negatively to chaos.
The second video shows you a little of what to do about that.
BREATHE -
breath rhythmically, evenly, and through the heart every day
View media item 1750339
On the right side of the page we have the body in negative, on the left, the body in positive mode.
The center vertical line is the span of energy from relaxed (bottom) to charged up, cold to hot.
- ACH to adrenaline.
The center horizontal line is the emotional states of positive or negative.
- Negative states are supported by cortisol, restricting cognitive coherence.
- Positive states are supported by DHEA, your body’s all ‘round performance enhancer. (the elixir of youth, the vitality hormone).
In the top and bottom corners you have the brain wave patterns of relaxed and energetic states.
- When you heat a body up in negative you get the emotions of anxiety, anger, frustration.
- Heat up a body in positive and you get things like, passion, determination, and focus.
Heart rates for both sides are 120 bpm, both have the same amount of adrenaline.
- Negative is erratic, positive is coherent.
- Negative biology will impair your performance, where positive biology will enhance it.
- Passion is the #1 predictor for performance across every aspect of life, including health.
Relaxation is not always healthy. In fact, relaxation in negative can kill you.
- Cool the body down in negative and you’ll find apathy, boredom, detachment, indifference
- Relaxed and positive puts you in the emotional states of contentment, curiosity, equanimity.
Heart rate for both sides is 50 bpm, but negative is erratic, positive is coherent.
What matters is which side your living on. Most people live on that right side, complaining and expecting the worst, insisting you pay attention to “reality.”
You can bring yourself from the negative side of erratic heartbeat and impaired thought to at least the center by simply focusing on your breathing, which will regulate your physiology. To get living on the positive side you take control of your emotional state.
Proper breathing focus:
1. Breath rhythmically. It doesn’t matter what the count, but make it longer on exhale and keep the rhythm constant.
2. Keep the breathing smooth and even, eliminating any tendency to be staccato.
3. Focus your breathing on your heart.
The heart is the strongest electrical output in the body, way ahead of the brain in the energetic output. The heart is also the focus of our positive emotions. Focusing your breathing in the heart enlivens the biology.
The “zone” and state of “flow” are on the left side of the page. A leaders job, should he/she accept it,
is to get the team living on the left side, in emotional control.I’m getting closer and closer to starting a breathing group in this building I live in.
Brian420pm
Well-Known Member
This is related and timely. I remembered something I heard in some yoga or meditation context, to "center" one's self. I didn't really get it until the other day a light bulb went off, I did exactly that and felt the amazing results!
First I closed my eyes and imagined where on my forehead the exact center lies, then touched it with my finger, then pulled it down slowly to the bridge of my nose. Your perceived center will not always be perfectly in the center of your forehead, which you'll notice right away, then your brain will naturally compensate by the time your finger reaches your nose.
Then I opened my eyes, I was laying back on a recliner, and I centered my body from head to toe as symmetrically as possible... both arms down and in the same exact but opposite position, legs the same way, torso perfectly flat on the recliner. As I closed my eyes I paid attention to the sounds of music coming from my speakers and the room I was in.
I took a very slow and deep breath, everything kinda clicked together at that moment... like a clarity, "Ahh, so THIS is what it feels like to be "centered"!
- Thread starter
- #785
That was sweet reading Brian. 
I could feel the moment.
I walk around centered most of the time. I have a new habit of stopping occasionally to take stock of how satisfied I’m feeling, with the intention to ramp it up a bit, no matter what level I find it.
“...balance, equilibrium, equanimity.” It’s part of my daily ritual to reinforce them.
I could feel the moment. I walk around centered most of the time. I have a new habit of stopping occasionally to take stock of how satisfied I’m feeling, with the intention to ramp it up a bit, no matter what level I find it.
“...balance, equilibrium, equanimity.” It’s part of my daily ritual to reinforce them.
- Thread starter
- #786
Trying to understand why limonene is alerting in cannabis when it’s activation of the A2A receptors is thought to create an environment of sedation. 
Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A2A receptors
Limonene is a major aromatic compound in essential oils extracted from citrus rind. The application of limonene, especially in aromatherapy, has expanded significantly, but its potential effects on cellular metabolism have been elusive. We found that limonene directly binds to the adenosine A(2A) receptor, which may induce sedative effects. Results from an in vitro radioligand binding assay showed that limonene exhibits selective affinity to A(2A) receptors. In addition, limonene increased cytosolic cAMP concentration and induced activation of protein kinase A and phosphorylation of cAMP-response element-binding protein in Chinese hamster ovary cells transfected with the human adenosine A(2A) receptor gene. Limonene also increased cytosolic calcium concentration, which can be achieved by the activation of adenosine A(2A) receptors. These findings suggest that limonene can act as a ligand and an agonist for adenosine A(2A) receptors.
... Limonene, a major component of citron EO, was found to directly bind to the adenosine A2A receptors. The activation of A2A receptors causes vasodilation in the aorta and coronary artery; inhibits platelet aggregation via activation of the protein kinase A (PKA) signaling pathway, and protects against tissue injury by reducing inflammation during reperfusion after ischemia, and shift- ing the balance between pro-inflammatory and anti-inflammatory cytokines in favor of the latter
Medicinal Plants Targeting Cardiovascular Diseases in View of Avicenna
... CBD is an agonist; limonene, a monoterpene, exhibits selective affinity, likely responsible for its sedative effect
... A2A receptors mediate glutamate uptake and neuropathic pain; they are neuroprotective, antinociceptive/ anti-inflammatory; reduce glutamate-, IL-6, TNFa-, COX-2, iNOS-release and attenuate brain damage in neurodegenerative disorders, inflammation of lung and retina, in vitro and in vivo. Agonists promote also angiogenesis, macrophage expression, collagen production and downregulate matrix metalloproteinase (MMP 9, 2, 14), which are involved in collagen breakdown (important in cancer), and increase Hepatic Stellate Cell (HSC) proliferation
Cannabidiol and Contributions of Major Hemp Phytocompounds to the “Entourage Effect”; Possible Mechanisms
... A2A receptors mediate glutamate uptake and neuropathic pain; they are neuroprotective, antinociceptive/ anti-inflammatory; reduce glutamate-, IL-6, TNFa-, COX-2, iNOS-release and attenuate brain damage in neurodegenerative disorders, inflammation of lung and retina, in vitro and in vivo. Agonists promote also angiogenesis, macrophage expression, collagen production and downregulate matrix metalloproteinase (MMP 9, 2, 14), which are involved in collagen breakdown (important in cancer), and increase Hepatic Stellate Cell (HSC) proliferation
Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A2A receptors
Limonene is a major aromatic compound in essential oils extracted from citrus rind. The application of limonene, especially in aromatherapy, has expanded significantly, but its potential effects on cellular metabolism have been elusive. We found that limonene directly binds to the adenosine A(2A) receptor, which may induce sedative effects. Results from an in vitro radioligand binding assay showed that limonene exhibits selective affinity to A(2A) receptors. In addition, limonene increased cytosolic cAMP concentration and induced activation of protein kinase A and phosphorylation of cAMP-response element-binding protein in Chinese hamster ovary cells transfected with the human adenosine A(2A) receptor gene. Limonene also increased cytosolic calcium concentration, which can be achieved by the activation of adenosine A(2A) receptors. These findings suggest that limonene can act as a ligand and an agonist for adenosine A(2A) receptors.
... Limonene, a major component of citron EO, was found to directly bind to the adenosine A2A receptors. The activation of A2A receptors causes vasodilation in the aorta and coronary artery; inhibits platelet aggregation via activation of the protein kinase A (PKA) signaling pathway, and protects against tissue injury by reducing inflammation during reperfusion after ischemia, and shift- ing the balance between pro-inflammatory and anti-inflammatory cytokines in favor of the latter
Medicinal Plants Targeting Cardiovascular Diseases in View of Avicenna
... CBD is an agonist; limonene, a monoterpene, exhibits selective affinity, likely responsible for its sedative effect
... A2A receptors mediate glutamate uptake and neuropathic pain; they are neuroprotective, antinociceptive/ anti-inflammatory; reduce glutamate-, IL-6, TNFa-, COX-2, iNOS-release and attenuate brain damage in neurodegenerative disorders, inflammation of lung and retina, in vitro and in vivo. Agonists promote also angiogenesis, macrophage expression, collagen production and downregulate matrix metalloproteinase (MMP 9, 2, 14), which are involved in collagen breakdown (important in cancer), and increase Hepatic Stellate Cell (HSC) proliferation
Cannabidiol and Contributions of Major Hemp Phytocompounds to the “Entourage Effect”; Possible Mechanisms
... A2A receptors mediate glutamate uptake and neuropathic pain; they are neuroprotective, antinociceptive/ anti-inflammatory; reduce glutamate-, IL-6, TNFa-, COX-2, iNOS-release and attenuate brain damage in neurodegenerative disorders, inflammation of lung and retina, in vitro and in vivo. Agonists promote also angiogenesis, macrophage expression, collagen production and downregulate matrix metalloproteinase (MMP 9, 2, 14), which are involved in collagen breakdown (important in cancer), and increase Hepatic Stellate Cell (HSC) proliferation
- Thread starter
- #787
This may be the answer:
The activation of A2A receptors causes vasodilation in the aorta and coronary artery;
Vasodilation may be responsible for the increased bioavailability of limonene, but if it’s sedating that would mean more tendency to be sleepy, wouldn’t it?
The activation of A2A receptors causes vasodilation in the aorta and coronary artery;
Vasodilation may be responsible for the increased bioavailability of limonene, but if it’s sedating that would mean more tendency to be sleepy, wouldn’t it?
- Thread starter
- #788
In neuroscience, glutamate refers to the anion of glutamic acid in its role as a neurotransmitter: a chemical that nerve cells use to send signals to other cells. It is by a wide margin the most abundant excitatory neurotransmitter in the vertebrate nervous system.
This may be my answer. Limonene assists in the uptake of glutamate.
This may be my answer. Limonene assists in the uptake of glutamate.
It may also be as simple as vasodilation causing a lowering of blood pressure, which causes sleepiness.
- Thread starter
- #790
Source
Physiol Behav. 2014 Aug;135:119-24. doi: 10.1016/j.physbeh.2014.06.003. Epub 2014 Jun 13.
β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice.
Recent evidence suggests that the cannabinoid receptor subtype 2 (CB2) is implicated in anxiety and depression disorders, although few systematic studies in laboratory animals have been reported. The aim of the current experiments was to test the effects of the CB2 receptor potent-selective agonist β-caryophyllene (BCP) in animals subjected to models of anxiolytic- and antidepressant-like effects. Therefore effects of BCP (50mg/kg) on anxiety were assessed using the elevated plus maze (EPM), open field (OF), and marble burying test (MBT). However for depression, the novelty-suppressed feeding (NSF), tail suspension test (TST), and forced swim tests (FST) were used. Results indicated that adult mice receiving BCP showed amelioration of all the parameters observed in the EPM test. Also, BCP significantly increased the time spent in the center of the arena without altering the general motor activity in the OF test. This dose was also able to decrease the number of buried marbles and time spent digging in the MBT, suggesting an anti-compulsive-like effect. In addition, the systemic administration of BCP reduced immobility time in the TST and the FST. Finally, BCP treatment decreased feeding latency in the NSF test. Most importantly, pre-administration of the CB2 receptor antagonist AM630, fully abrogated the anxiolytic and the anti-depressant effects of BCP. Taken together, these preclinical results suggest that CB2 receptors may provide alternative therapeutic targets for the treatment of anxiety and depression. The possibility that BCP may ameliorate the symptoms of these mood disorders offers exciting prospects for future studies.
Physiol Behav. 2014 Aug;135:119-24. doi: 10.1016/j.physbeh.2014.06.003. Epub 2014 Jun 13.
β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice.
Recent evidence suggests that the cannabinoid receptor subtype 2 (CB2) is implicated in anxiety and depression disorders, although few systematic studies in laboratory animals have been reported. The aim of the current experiments was to test the effects of the CB2 receptor potent-selective agonist β-caryophyllene (BCP) in animals subjected to models of anxiolytic- and antidepressant-like effects. Therefore effects of BCP (50mg/kg) on anxiety were assessed using the elevated plus maze (EPM), open field (OF), and marble burying test (MBT). However for depression, the novelty-suppressed feeding (NSF), tail suspension test (TST), and forced swim tests (FST) were used. Results indicated that adult mice receiving BCP showed amelioration of all the parameters observed in the EPM test. Also, BCP significantly increased the time spent in the center of the arena without altering the general motor activity in the OF test. This dose was also able to decrease the number of buried marbles and time spent digging in the MBT, suggesting an anti-compulsive-like effect. In addition, the systemic administration of BCP reduced immobility time in the TST and the FST. Finally, BCP treatment decreased feeding latency in the NSF test. Most importantly, pre-administration of the CB2 receptor antagonist AM630, fully abrogated the anxiolytic and the anti-depressant effects of BCP. Taken together, these preclinical results suggest that CB2 receptors may provide alternative therapeutic targets for the treatment of anxiety and depression. The possibility that BCP may ameliorate the symptoms of these mood disorders offers exciting prospects for future studies.
- Thread starter
- #791
In cannabis, limonene is what we look for with the expectation of a clear and creative euphoria. The strains I choose with the snap of citrus have never caused me to fall asleep.
I can see how mixing it with higher levels of myrcene might bring that about.The more I study the more there is to study. Lol!
- Thread starter
- #792
Source
Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans.
Corrigendum to "Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans" [Exp. Gerontol. 57 (2014) 81-95]. [Exp Gerontol. 2016]
Abstract
Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene and is a FDA approved food additive, found as an active ingredient in essential oils of numerous edible plants. It possesses a wide range of biological activities including anti-oxidant, anti-inflammatory, anti-cancerous and local anesthetic actions. We used the well established Caenorhabditis elegans model system to elucidate the stress modulatory and lifespan prolonging action of BCP. The present study for the first time reports the lifespan extension and stress modulation potential of BCP in C. elegans. Upon evaluation, it was found that 50μM dose of BCP increased the lifespan of C. elegans by over 22% (P≤0.0001) and significantly reduced intracellular free radical levels, maintaining cellular redox homeostasis. Moreover, the results suggest that BCP modulates feeding behavior, pharyngeal pumping and body size effectively. Further, this compound also exhibited significant reduction in intestinal lipofuscin levels. In the present investigation, we have predicted possible biological molecular targets for BCP using molecular docking approaches and BCP was found to have interaction with SIR-2.1, SKN-1 and DAF-16. The prediction was further validated in vivo using mutants and transgenic strains unraveling underlying genetic mechanism. It was observed that BCP increased lifespan of mev-1 and daf-16 but failed to augment lifespan in eat-2, sir-2.1 and skn-1 mutants. Relative quantification of mRNA demonstrated that several genes regulating oxidative stress, xenobiotic detoxification and longevity were modulated by BCP treatment. The study unravels the involvement of multiple signaling pathways in BCP mediated lifespan extension.
Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans.
Corrigendum to "Beta-caryophyllene modulates expression of stress response genes and mediates longevity in Caenorhabditis elegans" [Exp. Gerontol. 57 (2014) 81-95]. [Exp Gerontol. 2016]
Abstract
Beta-caryophyllene (BCP) is a natural bicyclic sesquiterpene and is a FDA approved food additive, found as an active ingredient in essential oils of numerous edible plants. It possesses a wide range of biological activities including anti-oxidant, anti-inflammatory, anti-cancerous and local anesthetic actions. We used the well established Caenorhabditis elegans model system to elucidate the stress modulatory and lifespan prolonging action of BCP. The present study for the first time reports the lifespan extension and stress modulation potential of BCP in C. elegans. Upon evaluation, it was found that 50μM dose of BCP increased the lifespan of C. elegans by over 22% (P≤0.0001) and significantly reduced intracellular free radical levels, maintaining cellular redox homeostasis. Moreover, the results suggest that BCP modulates feeding behavior, pharyngeal pumping and body size effectively. Further, this compound also exhibited significant reduction in intestinal lipofuscin levels. In the present investigation, we have predicted possible biological molecular targets for BCP using molecular docking approaches and BCP was found to have interaction with SIR-2.1, SKN-1 and DAF-16. The prediction was further validated in vivo using mutants and transgenic strains unraveling underlying genetic mechanism. It was observed that BCP increased lifespan of mev-1 and daf-16 but failed to augment lifespan in eat-2, sir-2.1 and skn-1 mutants. Relative quantification of mRNA demonstrated that several genes regulating oxidative stress, xenobiotic detoxification and longevity were modulated by BCP treatment. The study unravels the involvement of multiple signaling pathways in BCP mediated lifespan extension.
- Thread starter
- #793
From Medical Jane:
Terpenes are common constituents of flavorings and fragrances. Terpenes, unlike cannabinoids, are responsible for the aroma of cannabis. The FDA and other agencies have generally recognized terpenes as “safe.” Terpenes act on receptors and neurotransmitters; they are prone to combine with or dissolve in lipids or fats; they act as serotonin uptake inhibitors (similar to antidepressants like Prozac); they enhance norepinephrine activity (similar to tricyclic antidepressants like Elavil); they increase dopamine activity; and they augment GABA (the “downer” neurotransmitter that counters glutamate, the “upper”). However, more specific research is needed for improved accuracy in describing and predicting how terpenes in cannabis can be used medicinally to help treat specific ailments / health conditions.
Terpenes are common constituents of flavorings and fragrances. Terpenes, unlike cannabinoids, are responsible for the aroma of cannabis. The FDA and other agencies have generally recognized terpenes as “safe.” Terpenes act on receptors and neurotransmitters; they are prone to combine with or dissolve in lipids or fats; they act as serotonin uptake inhibitors (similar to antidepressants like Prozac); they enhance norepinephrine activity (similar to tricyclic antidepressants like Elavil); they increase dopamine activity; and they augment GABA (the “downer” neurotransmitter that counters glutamate, the “upper”). However, more specific research is needed for improved accuracy in describing and predicting how terpenes in cannabis can be used medicinally to help treat specific ailments / health conditions.
- Thread starter
- #794
It makes so much more sense now.
- Thread starter
- #795
Theory is terpenes are created to help a plant survive its environment. It’s somewhat serendipitous, if you believe in such random chance paying off this big, time that terpenes benefit the animal kingdom in so many ways:
- preventing cells from becoming cancerous
- destroying cancer cells
- repelling pathogens
- staving off invaders
- strengthening the immune system
- modulating the shape and response of protein receptors
- changing the permeability of cell membranes to allow molecules to flow through
- influencing the passageways in and out of cells
- encouraging the proprietary uptake of certain molecules
- preventing cell mutation
- influencing cell “switches “
- and on, and on, and on.......
I’d almost bet my life terpenes influence dimers, which can create entirely new pharmacological effects from signaling.
- preventing cells from becoming cancerous
- destroying cancer cells
- repelling pathogens
- staving off invaders
- strengthening the immune system
- modulating the shape and response of protein receptors
- changing the permeability of cell membranes to allow molecules to flow through
- influencing the passageways in and out of cells
- encouraging the proprietary uptake of certain molecules
- preventing cell mutation
- influencing cell “switches “
- and on, and on, and on.......
I’d almost bet my life terpenes influence dimers, which can create entirely new pharmacological effects from signaling.
- Thread starter
- #796
From Leafly:
What is CBDA (cannabidiolic acid) & what are the benefits of this cannabinoid?
Jacqueline HavelkaSeptember 16, 2019
“A number of stressors, including radiation and chemotherapy, trigger the body to release excess serotonin, causing nausea and vomiting. While vomiting can typically be controlled with medication, nausea is harder to control. Many cancer patients say that nausea causes much more distress than vomiting because nausea is a continuous sensation. In fact, one in five patients consider discontinuing cancer treatment so as to not experience the nausea.
Scientists have demonstrated that CBDA can affect the body’s 5-HT serotonin-producing receptors, hinting at a potential use for CBDA as a medication for chemotherapy-induced nausea/vomiting (CINV) and other conditions that induce these symptoms. However, more research is needed.”
Now I understand why, when I got really upset at the fisherman to the point that I was physically shaking it made me nauseous, so badly nauseous that I spent most of the night in agony.
Had I understood this I’d have tried smoking some Candida.
I have no desire to let myself get that upset again. I wasn’t mad at him anyway. That’s not the way these things go. I was mad at me, for trying to make him be someone neither one of us wanted him to be. Won’t be trying that again. Lol!
What is CBDA (cannabidiolic acid) & what are the benefits of this cannabinoid?
Jacqueline HavelkaSeptember 16, 2019
“A number of stressors, including radiation and chemotherapy, trigger the body to release excess serotonin, causing nausea and vomiting. While vomiting can typically be controlled with medication, nausea is harder to control. Many cancer patients say that nausea causes much more distress than vomiting because nausea is a continuous sensation. In fact, one in five patients consider discontinuing cancer treatment so as to not experience the nausea.
Scientists have demonstrated that CBDA can affect the body’s 5-HT serotonin-producing receptors, hinting at a potential use for CBDA as a medication for chemotherapy-induced nausea/vomiting (CINV) and other conditions that induce these symptoms. However, more research is needed.”
Now I understand why, when I got really upset at the fisherman to the point that I was physically shaking it made me nauseous, so badly nauseous that I spent most of the night in agony.
Had I understood this I’d have tried smoking some Candida.
I have no desire to let myself get that upset again. I wasn’t mad at him anyway. That’s not the way these things go.
I was mad at me, for trying to make him be someone neither one of us wanted him to be. Won’t be trying that again. Lol!- Thread starter
- #797
From last year. The way these guys write makes it drudgery time wade through. 
Let me see if I can make it easier to understand.
References can be found by following the link.
Cannabis and Pain
Ethan B Russo, MD
Pain Medicine, Volume 20, Issue 11, November 2019, Pages 2083–2085, Cannabis and Pain
Published:
14 September 2019
This editorial is occasioned by the publication in Pain Medicine of two quite distinct articles [1,2] on the topical subject of cannabis and pain. As a point of departure, it is necessary to define terms. Cannabis sativa L. is a highly variable biochemical and morphological plant frequently termed “marijuana,” an obsolete and pejorative terminology for an ancient Old World species that has been utilized as an analgesic for millennia. The cannabis of commerce is frequently divided into two categories termed “sativa” and “indica” that purport to refer to differences that are neither taxonomically nor pharmacologically defensible. Similarly, one may refer to “strains” of cannabis, a label that is properly applied to bacteria or viruses, but not plants. Rather, what is scientifically relevant is the biochemical profile of a given cannabis variety, prompting the more appropriate terminology of chemical varieties or “chemovars.”
The first entry [1] documents the contents of a 2016 pain symposium encompassing contributions of several experts on pain, addiction, and drugs of abuse. Although it certainly is the case that the participants outlined at length the theoretical dangers and pitfalls of cannabis, there is little allusion to first-hand experience with cannabis as medicine, and the overall impression created may be unnecessarily alarmist and particularly attributable to a conflation of the adverse event profile of recreational smoking of cannabis as compared with its therapeutic application in chronic pain patients. A few sweeping statements are necessary as a prelude (reviewed in [3,4]). Cannabis is unimpressive as an analgesic for acute pain, with the possible exceptions of treatment of paroxysmal or breakthrough pain or its adjunctive utilization in conjunction with opioids [5]. Rather, the benefit of cannabis in pain management is most apparent in patients with chronic conditions, particularly in those with neuropathic pain wherein opioids are suboptimally effective, or may even exacerbate the condition. Second, therapeutic use of cannabis is different in its aim and methods in comparison to recreational usage, wherein the entire point is to create a “high” or intoxication that must be considered a side effect in pain treatment, wherein the ideal result would be effective analgesia without alteration of consciousness or impairment. This seeming discrepancy is logically supported by the differences in methodology of dosing. Recreational cannabis is far and away linked to inhalation, usually by smoking, a technique that will never garner support in the medical or regulatory communities. After inhalation, a rapid pharmacokinetic peak activity is attained, but at the risk of intoxication, and the need for frequent redosing risks the production of reinforcement and dependency. The frequency of cannabis dependence is frequently cited based on US data as 9%, a figure that must be challenged and downgraded by up to 60% due to the fact that an equivalent number of cannabis users are placed in treatment for cannabis addiction through the legal system as an alternative to incarceration, irrespective of whether true dependency is operative in a given individual. The addiction risk of therapeutic cannabis usage, in contrast, approaches 0% in formal studies, particularly in that no mortality, serious sequelae, tolerance, dose escalation, or withdrawal has been documented [3]. Risks can be further reduced through utilization of proper extracts, particularly those containing cannabidiol (CBD), which counteracts the anxiety, tachycardia, dependency, and other potential pitfalls of excessive tetrahydrocannabinol (THC) exposure.
Although smoking and the more modern harm reduction technique of vaporization of cannabis remain popular in many countries for medical usage, the more defensible and actively pursued approach is rather the use of oral or oromucosally administered extracts of cannabis, inasmuch as these can provide measured doses of material that are more easily titrated to achieve pain control without untoward effects. Additional advantages are less frequent dosing and avoidance of peaks and valleys of effects. Additionally, proper blinding of cannabis-based medicines in randomized controlled trials is far easier with oral preparations and has proven extremely challenging in studies with inhaled materials.
Maher et al. [1] note the rapidly changing landscape of cannabis legalization and widespread usage. Subsequent to this conference, the National Academies of Science, Engineering and Medicine [6] opined in 2017 that “there is conclusive or substantial evidence that cannabis or cannabinoids are effective: for the treatment of chronic pain in adults (cannabis).” A significant part of the foundation for this decision is connected to nabiximols (Sativex), the oromucosal spray of standardized whole cannabis extracts containing THC and CBD in roughly a 1:1 ratio, which is approved in 30 countries (other than the United States) for treatment of medically refractory spasticity in multiple sclerosis; it is additionally approved in Canada under a Notice of Compliance with Conditions (NOC/c) for MS-associated central neuropathic pain and for cancer pain unresponsive to optimized opioid treatment. The latter indication was supported by two Phase II clinical trials, but without overall success in three subsequent Phase III trials [3]. Additional scrutiny of the data are necessary, however, in that stratification of the patients by country of origin revealed that significant pain reduction was achieved in the American cohort but not in other countries [7]. The distinction seems to be rooted in marked differences in patient profiles, specifically in that American patients had less severe Karnofsky impairment levels at baseline and freer access to opioids, in contrast to the sicker Eastern European cohort, where opioid intervention was a later and less available option. An additional important observation from the nabiximols program is frequently overlooked in that it was derived from a long-term safety extension publication rather than a placebo-controlled trial [8]. In this study, hospice patients with cancer on nabiximols not only failed to increase that dosage with progression of their disease, but also failed to demonstrate the expected increases in opioid dosages before succumbing to their illness.
The second entry in this issue on cannabis and pain [2] is provided by a team in Israel with many years of experience in treatment with cannabis. I can imagine my colleagues scoffing at the concept of accepting as evidence a series of anecdotal interviews in an era where the randomized controlled trial is the sine qua non of medical proof. However, it must be urged that readers descend from the ivory tower for a few moments and that disbelief be temporarily suspended to listen to the imparted messages. Certain basic truths must be advanced: 1) we are facing a opioid crisis with attendant unacceptable iatrogenic mortality; 2) our nonopioid alternatives are minimally effective adjuncts in the treatment of chronic pain and often harbor their own prominent comorbidities and sequelae; 3) there are no data that support the safety or efficacy of long-term opioids in chronic noncancer pain; 4) little is on the drug development horizon that portends to alter this landscape; 5) whether anyone likes it or not, increasing millions of people around the globe are utilizing cannabis to treat their pain, and observational studies and surveys repeatedly demonstrate that pain is the top medical indication for cannabis usage, in the range of 70% of all patients; 6) no medicine is successful commercially or otherwise unless the patient perceives that they are improved through its usage; and 7) as we lack objective measurement of pain on the clinical front (the putative “pain-o-meter”), we have only the patients’ opinions and those of their caregivers to guide measures of efficacy.
Given this situation confronting the pain clinician, patient experience is of paramount importance. Lavie-Ajayi and Shvartzman document the measures of relief of pain espoused by their clientele. Often these are accompanied by unfamiliar terminology. The 19 patients interviewed were all long-term chronic pain sufferers utilizing 20–60 grams of cannabis per month (2/3–2 g/d). Acute reaction to dosing often produced a “sigh of relief” associated with pain abatement. This was accompanied by improvement in mood, a degree of relaxation, and a sense that while the pain might still be present, even unabated in intensity in some instances, rather it became tolerable, allowing a compartmentalization and distancing from the emotional ballast that customarily drags the chronic pain patient into a pit of despair. Physiologically, this phenomenon is easily explained on the basis that CB1 receptors are densely represented in the limbic system areas that are responsible for the affective elements of pain perception. If such relief is realized on a regular basis, this allows “a return to normality,” which could entail goals such as increased engagement with family, friends, and activities previously avoided before treatment. Overall, the result was a sense of “restored self,” a status that most chronic pain patients lose hope of ever attaining once more.
Such findings may smack of “new age” ethos to many but will be eminently familiar to those clinicians with exposure to significant populations of clinical cannabis patients. There is a tendency to disbelieve in magic, but that term cannot be properly applied to cannabis, wherein the theoretical basis for its analgesic effects is so extensive [3] and adoption by the public is advancing at a phenomenal pace. Let us be clear: Cannabis is not laetrile. This is not a matter of collective delusion, nor some conspiratorial smokescreen. A recent experiment demonstrates the real-time opioid-sparing efficacy of THC with oxycodone [5], whereas a plethora of observational studies document opioid and other adjunctive drug reduction or discontinuation in large numbers of patients with chronic pain conditions, including fibromyalgia [9]. It requires emphasis that many such results have often been attained with unstandardized cannabis chemovars, and not with agents that have been selectively bred to enhance analgesic efficacy through combinations of the most efficacious components to reduce pain (THC, CBD, beta-caryophyllene) or minimize adverse events (CBD, limonene, alpha-pinene, linalool).
The time has passed when it is justifiable for pain clinics in cannabis legal jurisdictions to discharge patients for the appearance of THC metabolites in their urine. I urge clinicians to educate themselves on cannabis, cannabinoids, and the endocannabinoid system, to understand that cannabis is a variable botanical with distinct pharmacological differences between chemovars with attendant preparation-specific effects, and to engage their patients in substantive discussions of the impact that cannabis may have on their quality of life.
Funding sources: Ethan Russo is Director of Research and Development for ICCI with no additional funding for this editorial.
The way these guys write makes it drudgery time wade through. Let me see if I can make it easier to understand. References can be found by following the link.
Cannabis and Pain
Ethan B Russo, MD
Pain Medicine, Volume 20, Issue 11, November 2019, Pages 2083–2085, Cannabis and Pain
Published:
14 September 2019
This editorial is occasioned by the publication in Pain Medicine of two quite distinct articles [1,2] on the topical subject of cannabis and pain. As a point of departure, it is necessary to define terms. Cannabis sativa L. is a highly variable biochemical and morphological plant frequently termed “marijuana,” an obsolete and pejorative terminology for an ancient Old World species that has been utilized as an analgesic for millennia. The cannabis of commerce is frequently divided into two categories termed “sativa” and “indica” that purport to refer to differences that are neither taxonomically nor pharmacologically defensible. Similarly, one may refer to “strains” of cannabis, a label that is properly applied to bacteria or viruses, but not plants. Rather, what is scientifically relevant is the biochemical profile of a given cannabis variety, prompting the more appropriate terminology of chemical varieties or “chemovars.”
The first entry [1] documents the contents of a 2016 pain symposium encompassing contributions of several experts on pain, addiction, and drugs of abuse. Although it certainly is the case that the participants outlined at length the theoretical dangers and pitfalls of cannabis, there is little allusion to first-hand experience with cannabis as medicine, and the overall impression created may be unnecessarily alarmist and particularly attributable to a conflation of the adverse event profile of recreational smoking of cannabis as compared with its therapeutic application in chronic pain patients. A few sweeping statements are necessary as a prelude (reviewed in [3,4]). Cannabis is unimpressive as an analgesic for acute pain, with the possible exceptions of treatment of paroxysmal or breakthrough pain or its adjunctive utilization in conjunction with opioids [5]. Rather, the benefit of cannabis in pain management is most apparent in patients with chronic conditions, particularly in those with neuropathic pain wherein opioids are suboptimally effective, or may even exacerbate the condition. Second, therapeutic use of cannabis is different in its aim and methods in comparison to recreational usage, wherein the entire point is to create a “high” or intoxication that must be considered a side effect in pain treatment, wherein the ideal result would be effective analgesia without alteration of consciousness or impairment. This seeming discrepancy is logically supported by the differences in methodology of dosing. Recreational cannabis is far and away linked to inhalation, usually by smoking, a technique that will never garner support in the medical or regulatory communities. After inhalation, a rapid pharmacokinetic peak activity is attained, but at the risk of intoxication, and the need for frequent redosing risks the production of reinforcement and dependency. The frequency of cannabis dependence is frequently cited based on US data as 9%, a figure that must be challenged and downgraded by up to 60% due to the fact that an equivalent number of cannabis users are placed in treatment for cannabis addiction through the legal system as an alternative to incarceration, irrespective of whether true dependency is operative in a given individual. The addiction risk of therapeutic cannabis usage, in contrast, approaches 0% in formal studies, particularly in that no mortality, serious sequelae, tolerance, dose escalation, or withdrawal has been documented [3]. Risks can be further reduced through utilization of proper extracts, particularly those containing cannabidiol (CBD), which counteracts the anxiety, tachycardia, dependency, and other potential pitfalls of excessive tetrahydrocannabinol (THC) exposure.
Although smoking and the more modern harm reduction technique of vaporization of cannabis remain popular in many countries for medical usage, the more defensible and actively pursued approach is rather the use of oral or oromucosally administered extracts of cannabis, inasmuch as these can provide measured doses of material that are more easily titrated to achieve pain control without untoward effects. Additional advantages are less frequent dosing and avoidance of peaks and valleys of effects. Additionally, proper blinding of cannabis-based medicines in randomized controlled trials is far easier with oral preparations and has proven extremely challenging in studies with inhaled materials.
Maher et al. [1] note the rapidly changing landscape of cannabis legalization and widespread usage. Subsequent to this conference, the National Academies of Science, Engineering and Medicine [6] opined in 2017 that “there is conclusive or substantial evidence that cannabis or cannabinoids are effective: for the treatment of chronic pain in adults (cannabis).” A significant part of the foundation for this decision is connected to nabiximols (Sativex), the oromucosal spray of standardized whole cannabis extracts containing THC and CBD in roughly a 1:1 ratio, which is approved in 30 countries (other than the United States) for treatment of medically refractory spasticity in multiple sclerosis; it is additionally approved in Canada under a Notice of Compliance with Conditions (NOC/c) for MS-associated central neuropathic pain and for cancer pain unresponsive to optimized opioid treatment. The latter indication was supported by two Phase II clinical trials, but without overall success in three subsequent Phase III trials [3]. Additional scrutiny of the data are necessary, however, in that stratification of the patients by country of origin revealed that significant pain reduction was achieved in the American cohort but not in other countries [7]. The distinction seems to be rooted in marked differences in patient profiles, specifically in that American patients had less severe Karnofsky impairment levels at baseline and freer access to opioids, in contrast to the sicker Eastern European cohort, where opioid intervention was a later and less available option. An additional important observation from the nabiximols program is frequently overlooked in that it was derived from a long-term safety extension publication rather than a placebo-controlled trial [8]. In this study, hospice patients with cancer on nabiximols not only failed to increase that dosage with progression of their disease, but also failed to demonstrate the expected increases in opioid dosages before succumbing to their illness.
The second entry in this issue on cannabis and pain [2] is provided by a team in Israel with many years of experience in treatment with cannabis. I can imagine my colleagues scoffing at the concept of accepting as evidence a series of anecdotal interviews in an era where the randomized controlled trial is the sine qua non of medical proof. However, it must be urged that readers descend from the ivory tower for a few moments and that disbelief be temporarily suspended to listen to the imparted messages. Certain basic truths must be advanced: 1) we are facing a opioid crisis with attendant unacceptable iatrogenic mortality; 2) our nonopioid alternatives are minimally effective adjuncts in the treatment of chronic pain and often harbor their own prominent comorbidities and sequelae; 3) there are no data that support the safety or efficacy of long-term opioids in chronic noncancer pain; 4) little is on the drug development horizon that portends to alter this landscape; 5) whether anyone likes it or not, increasing millions of people around the globe are utilizing cannabis to treat their pain, and observational studies and surveys repeatedly demonstrate that pain is the top medical indication for cannabis usage, in the range of 70% of all patients; 6) no medicine is successful commercially or otherwise unless the patient perceives that they are improved through its usage; and 7) as we lack objective measurement of pain on the clinical front (the putative “pain-o-meter”), we have only the patients’ opinions and those of their caregivers to guide measures of efficacy.
Given this situation confronting the pain clinician, patient experience is of paramount importance. Lavie-Ajayi and Shvartzman document the measures of relief of pain espoused by their clientele. Often these are accompanied by unfamiliar terminology. The 19 patients interviewed were all long-term chronic pain sufferers utilizing 20–60 grams of cannabis per month (2/3–2 g/d). Acute reaction to dosing often produced a “sigh of relief” associated with pain abatement. This was accompanied by improvement in mood, a degree of relaxation, and a sense that while the pain might still be present, even unabated in intensity in some instances, rather it became tolerable, allowing a compartmentalization and distancing from the emotional ballast that customarily drags the chronic pain patient into a pit of despair. Physiologically, this phenomenon is easily explained on the basis that CB1 receptors are densely represented in the limbic system areas that are responsible for the affective elements of pain perception. If such relief is realized on a regular basis, this allows “a return to normality,” which could entail goals such as increased engagement with family, friends, and activities previously avoided before treatment. Overall, the result was a sense of “restored self,” a status that most chronic pain patients lose hope of ever attaining once more.
Such findings may smack of “new age” ethos to many but will be eminently familiar to those clinicians with exposure to significant populations of clinical cannabis patients. There is a tendency to disbelieve in magic, but that term cannot be properly applied to cannabis, wherein the theoretical basis for its analgesic effects is so extensive [3] and adoption by the public is advancing at a phenomenal pace. Let us be clear: Cannabis is not laetrile. This is not a matter of collective delusion, nor some conspiratorial smokescreen. A recent experiment demonstrates the real-time opioid-sparing efficacy of THC with oxycodone [5], whereas a plethora of observational studies document opioid and other adjunctive drug reduction or discontinuation in large numbers of patients with chronic pain conditions, including fibromyalgia [9]. It requires emphasis that many such results have often been attained with unstandardized cannabis chemovars, and not with agents that have been selectively bred to enhance analgesic efficacy through combinations of the most efficacious components to reduce pain (THC, CBD, beta-caryophyllene) or minimize adverse events (CBD, limonene, alpha-pinene, linalool).
The time has passed when it is justifiable for pain clinics in cannabis legal jurisdictions to discharge patients for the appearance of THC metabolites in their urine. I urge clinicians to educate themselves on cannabis, cannabinoids, and the endocannabinoid system, to understand that cannabis is a variable botanical with distinct pharmacological differences between chemovars with attendant preparation-specific effects, and to engage their patients in substantive discussions of the impact that cannabis may have on their quality of life.
Funding sources: Ethan Russo is Director of Research and Development for ICCI with no additional funding for this editorial.
- Thread starter
- #798
Strainprint has a report on cannabis and polypharmacy that’s incredibly insightful. Highly recommended reading. 
- Thread starter
- #799
References can be found by following the link.
Cannabis and Pain
Ethan B Russo, MD
Pain Medicine, Volume 20, Issue 11, November 2019, Pages 2083–2085, Cannabis and Pain
Published:
14 September 2019
This editorial is occasioned by the publication in Pain Medicine of two quite distinct articles [1,2] on the topical subject of cannabis and pain. As a point of departure, it is necessary to define terms.
Cannabis sativa L. is a highly variable biochemical and morphological plant
The cannabis of commerce is frequently divided into two categories termed
purport to refer to differences that are neither taxonomically nor pharmacologically defensible.
Similarly, one may refer to “strains” of cannabis, a label that is properly applied to bacteria or viruses, but not plants. Rather, what is scientifically relevant is the biochemical profile of a given cannabis variety, prompting the more appropriate terminology of chemical varieties or “chemovars.”
The first entry [1] documents the contents of a 2016 pain symposium encompassing contributions of several experts on pain, addiction, and drugs of abuse. Although it certainly is the case that the participants outlined at length the theoretical dangers and pitfalls of cannabis,
A few sweeping statements are necessary as a prelude (reviewed in [3,4]).
Rather, the benefit of cannabis in pain management is most apparent in patients with chronic conditions, particularly in those with neuropathic pain wherein opioids are suboptimally effective, or may even exacerbate the condition.
Second, therapeutic use of cannabis is different in its aim and methods in comparison to recreational usage,
This seeming discrepancy is logically supported by the differences in methodology of dosing.
After inhalation, a rapid pharmacokinetic peak activity is attained, but
The frequency of cannabis dependence is frequently cited based on US data as 9%,
a figure that must be challenged and downgraded by up to 60%
The addiction risk of therapeutic cannabis usage, in contrast, approaches 0% in formal studies,
Risks can be further reduced through utilization of proper extracts, particularly those containing cannabidiol (CBD),
Although smoking and the more modern harm reduction technique of vaporization of cannabis remain popular in many countries for medical usage,
the more defensible and actively pursued approach is rather the use of oral or oromucosally administered extracts of cannabis,
Maher et al. [1] note the rapidly changing landscape of cannabis legalization and widespread usage. Subsequent to this conference, the National Academies of Science, Engineering and Medicine [6] opined in 2017 that “there is conclusive or substantial evidence that cannabis or cannabinoids are effective: for the treatment of chronic pain in adults (cannabis).”
A significant part of the foundation for this decision is connected to nabiximols (Sativex), the oromucosal spray of standardized whole cannabis extracts containing THC and CBD in roughly a 1:1 ratio,
Additional scrutiny of the data are necessary, however, in that stratification of the patients by country of origin revealed that significant pain reduction was achieved in the American cohort but not in other countries [7].
The distinction seems to be rooted in marked differences in patient profiles, specifically in that
The second entry in this issue on cannabis and pain [2] is provided by a team in Israel with many years of experience in treatment with cannabis. I can imagine my colleagues scoffing at the concept of accepting as evidence a series of anecdotal interviews in an era where the randomized controlled trial is the sine qua non of medical proof.
However, it must be urged that readers descend from the ivory tower for a few moments and that disbelief be temporarily suspended to listen to the imparted messages.
Certain basic truths must be advanced:
Given this situation confronting the pain clinician, patient experience is of paramount importance.
Lavie-Ajayi and Shvartzman document the measures of relief of pain espoused by their clientele. Often these are accompanied by unfamiliar terminology.
The 19 patients interviewed were all long-term chronic pain sufferers
Such findings may smack of “new age” ethos to many but will be eminently familiar to those clinicians with exposure to significant populations of clinical cannabis patients.
There is a tendency to disbelieve in magic, but that term cannot be properly applied to cannabis, wherein
and not with agents that have been selectively bred to enhance analgesic efficacy
The time has passed when it is justifiable for pain clinics in cannabis legal jurisdictions to discharge patients for the appearance of THC metabolites in their urine.
I urge clinicians to educate themselves on cannabis, cannabinoids, and the endocannabinoid system, to understand that
cannabis is a variable botanical
Funding sources: Ethan Russo is Director of Research and Development for ICCI with no additional funding for this editorial.
Cannabis and Pain
Ethan B Russo, MD
Pain Medicine, Volume 20, Issue 11, November 2019, Pages 2083–2085, Cannabis and Pain
Published:
14 September 2019
This editorial is occasioned by the publication in Pain Medicine of two quite distinct articles [1,2] on the topical subject of cannabis and pain. As a point of departure, it is necessary to define terms.
Cannabis sativa L. is a highly variable biochemical and morphological plant
- frequently termed “marijuana,” an obsolete and pejorative terminology for an ancient Old World species that has been utilized as an analgesic for millennia.
The cannabis of commerce is frequently divided into two categories termed
- “sativa” and
- “indica” that
purport to refer to differences that are neither taxonomically nor pharmacologically defensible.
Similarly, one may refer to “strains” of cannabis, a label that is properly applied to bacteria or viruses, but not plants. Rather, what is scientifically relevant is the biochemical profile of a given cannabis variety, prompting the more appropriate terminology of chemical varieties or “chemovars.”
The first entry [1] documents the contents of a 2016 pain symposium encompassing contributions of several experts on pain, addiction, and drugs of abuse. Although it certainly is the case that the participants outlined at length the theoretical dangers and pitfalls of cannabis,
* there is little allusion to first-hand experience with cannabis as medicine, and
* the overall impression created may be unnecessarily alarmist and
* particularly attributable to a conflation of the adverse event profile of recreational smoking of cannabis as compared with its therapeutic application in chronic pain patients.
A few sweeping statements are necessary as a prelude (reviewed in [3,4]).
*Cannabis is unimpressive as an analgesic for acute pain,
with the possible exceptions of - treatment of paroxysmal or breakthrough pain or
- its adjunctive utilization in conjunction with opioids [5].
Rather, the benefit of cannabis in pain management is most apparent in patients with chronic conditions, particularly in those with neuropathic pain wherein opioids are suboptimally effective, or may even exacerbate the condition.
Second, therapeutic use of cannabis is different in its aim and methods in comparison to recreational usage,
* wherein the entire point is to create a “high” or intoxication that
****must be considered a side effect in pain treatment, ****
- wherein the ideal result would be effective analgesia without alteration of consciousness or impairment.
This seeming discrepancy is logically supported by the differences in methodology of dosing.
* Recreational cannabis is far and away linked to inhalation,
*usually by smoking, a
* technique that will never garner support in the medical or regulatory communities.
After inhalation, a rapid pharmacokinetic peak activity is attained, but
*at the risk of intoxication, and
* the need for frequent redosing risks
*the production of reinforcement and dependency.
The frequency of cannabis dependence is frequently cited based on US data as 9%,
a figure that must be challenged and downgraded by up to 60%
* due to the fact that an equivalent number of cannabis users are placed in treatment for cannabis addiction through the legal system as an alternative to incarceration, irrespective of whether true dependency is operative in a given individual.
The addiction risk of therapeutic cannabis usage, in contrast, approaches 0% in formal studies,
* particularly in that no mortality,
* serious sequelae,
* tolerance,
* tolerance,
* dose escalation,
* or withdrawal
has been documented [3]. Risks can be further reduced through utilization of proper extracts, particularly those containing cannabidiol (CBD),
* which counteracts the anxiety,
*tachycardia,
*dependency,
*and other potential pitfalls of excessive tetrahydrocannabinol (THC) exposure.
Although smoking and the more modern harm reduction technique of vaporization of cannabis remain popular in many countries for medical usage,
the more defensible and actively pursued approach is rather the use of oral or oromucosally administered extracts of cannabis,
* inasmuch as these can provide measured doses of material that are more easily titrated to achieve pain control without untoward effects.
*Additional advantages are less frequent dosing
*Additional advantages are less frequent dosing
*and avoidance of peaks and valleys of effects.
*Additionally, proper blinding of cannabis-based medicines in randomized controlled trials is far easier with oral preparations and has proven extremely challenging in studies with inhaled materials.
*Additionally, proper blinding of cannabis-based medicines in randomized controlled trials is far easier with oral preparations and has proven extremely challenging in studies with inhaled materials.
Maher et al. [1] note the rapidly changing landscape of cannabis legalization and widespread usage. Subsequent to this conference, the National Academies of Science, Engineering and Medicine [6] opined in 2017 that “there is conclusive or substantial evidence that cannabis or cannabinoids are effective: for the treatment of chronic pain in adults (cannabis).”
A significant part of the foundation for this decision is connected to nabiximols (Sativex), the oromucosal spray of standardized whole cannabis extracts containing THC and CBD in roughly a 1:1 ratio,
*which is approved in 30 countries (other than the United States) for treatment of medically refractory spasticity in multiple sclerosis;
* it is additionally approved in Canada under a Notice of Compliance with Conditions (NOC/c) for MS-associated central neuropathic pain
* and for cancer pain unresponsive to optimized opioid treatment.
The latter indication was supported by two Phase II clinical trials, but without overall success in three subsequent Phase III trials [3]. Additional scrutiny of the data are necessary, however, in that stratification of the patients by country of origin revealed that significant pain reduction was achieved in the American cohort but not in other countries [7].
The distinction seems to be rooted in marked differences in patient profiles, specifically in that
* American patients had less severe Karnofsky impairment levels at baseline
* and freer access to opioids,
* in contrast to the sicker Eastern European cohort, where opioid intervention was a later
* and less available option.
An additional important observation from the nabiximols program is frequently overlooked in that it was derived from a long-term safety extension publication rather than a placebo-controlled trial [8]. In this study, * hospice patients with cancer on nabiximols not only failed to increase that dosage with progression of their disease,
* but also failed to demonstrate the expected increases in opioid dosages before succumbing to their illness.
The second entry in this issue on cannabis and pain [2] is provided by a team in Israel with many years of experience in treatment with cannabis. I can imagine my colleagues scoffing at the concept of accepting as evidence a series of anecdotal interviews in an era where the randomized controlled trial is the sine qua non of medical proof.
However, it must be urged that readers descend from the ivory tower for a few moments and that disbelief be temporarily suspended to listen to the imparted messages.
Certain basic truths must be advanced:
1) we are facing a opioid crisis with attendant unacceptable iatrogenic mortality;
2) our nonopioid alternatives are minimally effective adjuncts in the treatment of chronic pain and often harbor their own prominent comorbidities and sequelae;
2) our nonopioid alternatives are minimally effective adjuncts in the treatment of chronic pain and often harbor their own prominent comorbidities and sequelae;
3) there are no data that support the safety or efficacy of long-term opioids in chronic noncancer pain;
4) little is on the drug development horizon that portends to alter this landscape;
5) whether anyone likes it or not, increasing millions of people around the globe are utilizing cannabis to treat their pain, and
* *observational studies and surveys repeatedly demonstrate that pain is the top medical indication for cannabis usage, in the range of 70% of all patients;
6) no medicine is successful commercially or otherwise unless the patient perceives that they are improved through its usage; and
7) as we lack objective measurement of pain on the clinical front (the putative “pain-o-meter”), we have only the patients’ opinions and those of their caregivers to guide measures of efficacy.
Given this situation confronting the pain clinician, patient experience is of paramount importance.
Lavie-Ajayi and Shvartzman document the measures of relief of pain espoused by their clientele. Often these are accompanied by unfamiliar terminology.
The 19 patients interviewed were all long-term chronic pain sufferers
* utilizing 20–60 grams of cannabis per month (2/3–2 g/d).
* Acute reaction to dosing often produced a “sigh of relief” associated with pain abatement.
* This was accompanied by improvement in mood,
* Acute reaction to dosing often produced a “sigh of relief” associated with pain abatement.
* This was accompanied by improvement in mood,
* a degree of relaxation,
* and a sense that while the pain might still be present, even unabated in intensity in some instances, rather it became tolerable,
* allowing a compartmentalization and distancing from the emotional ballast that customarily drags the chronic pain patient into a pit of despair.
Physiologically, this phenomenon is easily explained on the basis that CB1 receptors are densely represented in the limbic system areas that are responsible for the affective elements of pain perception.
If such relief is realized on a regular basis, this allows “a return to normality,” * which could entail goals such as increased engagement with family, friends, and activities previously avoided before treatment.
*Overall, the result was a sense of “restored self,” a status that most chronic pain patients lose hope of ever attaining once more.
*Overall, the result was a sense of “restored self,” a status that most chronic pain patients lose hope of ever attaining once more.
Such findings may smack of “new age” ethos to many but will be eminently familiar to those clinicians with exposure to significant populations of clinical cannabis patients.
There is a tendency to disbelieve in magic, but that term cannot be properly applied to cannabis, wherein
* the theoretical basis for its analgesic effects is so extensive [3]
* and adoption by the public is advancing at a phenomenal pace.
Let us be clear: Cannabis is not laetrile. This is not a matter of collective delusion, nor some conspiratorial smokescreen.* A recent experiment demonstrates the real-time opioid-sparing efficacy of THC with oxycodone [5],
*whereas a plethora of observational studies document opioid and other adjunctive drug reduction or discontinuation in large numbers of patients with chronic pain conditions,
* including fibromyalgia [9].
* It requires emphasis that many such results have often been attained with unstandardized cannabis chemovars,
* It requires emphasis that many such results have often been attained with unstandardized cannabis chemovars,
and not with agents that have been selectively bred to enhance analgesic efficacy
* through combinations of the most efficacious components to reduce pain (THC, CBD, beta-caryophyllene)
* or minimize adverse events (CBD, limonene, alpha-pinene, linalool).
The time has passed when it is justifiable for pain clinics in cannabis legal jurisdictions to discharge patients for the appearance of THC metabolites in their urine.
I urge clinicians to educate themselves on cannabis, cannabinoids, and the endocannabinoid system, to understand that
cannabis is a variable botanical
* with distinct pharmacological differences between chemovars
* with attendant preparation-specific effects, and
to engage their patients in substantive discussions of the impact that cannabis may have on their quality of life.Funding sources: Ethan Russo is Director of Research and Development for ICCI with no additional funding for this editorial.
- Thread starter
- #800
I‘ll dig out the high points from Strainprint tomorrow. I’m beat.
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