CBD efficacy on nonmotor symptoms of Parkinson Disease anxiety & psychosis


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This is the last section of a review article Managing Psychosis in Parkinson Disease

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Results from preclinical and preliminary studies also suggest that cannabidiol (CBD) has therapeutic potential for nonmotor symptoms of PD.14 The multifaceted mechanism of action as an agonist of 5-HT1A, partial agonist of CB1 and CB2 receptors, and antagonist of the G-protein–coupled receptor GPR55 reverses the iron-induced epigenetic modification of mitochondrial DNA and the reduction of succinate dehydrogenase activity and decreases the levels of the pro-inflammatory cytokines IL-1β, TNF-α, IFN-β, IFN-γ, IL-17, and IL-6—all of which decrease pro-inflammatory mediators resulting in neuroprotective, anxiolytic, and antipsychotic effects.14

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“Several in vitro experiments have demonstrated promising neuro- protective effects of CBD in PD models. In one of these models, using PC12 and SH-SY5Y cells treated with MPP+ [1-methyl-4-phenylpyridinium], CBD increased cell viability, differentiation, and the expression of axonal [GAP-43] and synaptic [synaptophysin and synapsin I] proteins,” Ferreria-Junior and colleagues wrote,15 while acknowledging the paucity of studies that have addressed the biological bases for the purported effects of CBD on PD. “Double-blind, placebo-controlled, randomized trials with larger samples of patients with PD are needed to elucidate the possible effectiveness and mechanisms involved in the therapeutic potential of CBD in this movement disorder. This will also include the putative effects of CBD in preventing L-dopa–induced severe [adverse] effects and preventing PD progression.”

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The endocannabinoid system serves as an important filter of excitatory, inhibitory, and modulatory inputs that act at the midbrain and terminal regions to orchestrate DA neurotransmission by controlling DA cell body firing patterns, terminal release, and effects on postsynaptic sites in the striatum.16 Beneficial effects of CBD administration have been observed prior to or immediately after induction of PD-like symptoms in animal studies, which may suggest a preventive role rather than a therapeutic one.14 In an early open-label pilot study to evaluate the efficacy of CBD on nonmotor symptoms of PD in 6 patients with PDP, psychotic symptoms significantly decreased under CBD treatment, as evaluated by the brief psychiatric rating scale and the Parkinson psychosis questionnaire.17

 

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Psychiatric comorbidities prevalent in the majority of patients with PD are associated with more disease severity, impaired QOL, and increased use of healthcare resources, with longer hospital stays and re-hospitalizations adding to the total cost burden.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  

Welcome to my Weblog on Pain Management!

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Simply Calming


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First, an introduction or just skip below to web link, below, of the sweet Suzuki Roshi breathing practice of exhalation. It is so simple people with Alzheimer’s can do it. So instantly calming.

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It is best to practice while we are young and build a solid practice, make it part of being with your Self. The Divine Self. It is so simple and so sweet. It is who we are.

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A wonderful practice and highest teaching. We are all the divine essence, the serene soul. Enjoy how simple and calming…..relax and be in the moment of which the highest teachings speak, as far back as the Vedas and Upanishads, Buddha and all spiritual traditions have taught. 

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There is no god but God. There are no other gods. Not dreamy woo woo stuff. It just Is. Omnipresent. 

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“This is no world. It is God Himself. In delusion we call it world.” Vivekananda (6:371) “Complete self-surrender is the only way to spiritual illumination. Vivekananda (5:258)

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Acceptance. Enjoy who you already are. 

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Just be. You are That. We forget our true self. This is real. No kids play. 

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We all experience these moments. Being. Just being. Simple as breathing. 

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“ There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

 

The Upanishads describe that stage as turiya pure consciousness. Turiya is the background that underlies and transcends the three common states of consciousness.

Buddhists call this emptiness. Advaita calls it fullness. The Divine Essence. God. The self that merges into the Absolute beyond, time space and causation Beyond name and form there is nothing else but the Self, Existence-Consciousness-Bliss. And this pure simple breathing out brings it into this very moment.

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from the dharma message of Zen priest and teacher White Lotus Judith Ragir.

click above name to go directly to the website for this  dharma teaching – it will be easier to read. 

 

Exhaling and dissolving.

Here are some quotes from Suzuki Roshi in “Not Always So” (chapter: Calmness of Mind) that emphasize working with the exhale while meditating:

Calmness of mind is beyond the end of your exhalation. If you exhale smoothly, without even trying to exhale, you are entering into the complete perfect calmness of your mind. You do not exist anymore. 

Inhaling without effort you naturally come back to yourself with some color or form. Exhaling, you gradually fade into emptiness – empty, white paper. That is shikantaza. The important point is your exhalation. Instead of trying to feel yourself as you inhale, fade into emptiness as you exhale. 

To take care of the exhalation is very important. To die is more important than trying to be alive. When we always try to be alive, we have trouble. Rather than trying to be alive or active, if we can be calm and die or fade away into emptiness, then naturally we will be all right. Buddha will take care of us. Because we have lost our mother’s bosom, we do not feel like her child anymore. Yet fading away into emptiness can feel like being at our mother’s bosom, and we will feel as though she will take care of us. Moment after moment, do not lose this practice of shikantaza.” 

This is very impressive quote to me. It is in alignment with the fourth Tetrad of the Anapanasati Sutra. The Anapanasati Sutra is composed of sixteen contemplations, which divide rather neatly into four sets of four: The body group, the feelings group, the mind group, and the wisdom group. They are in a “somewhat” developmental order in that mindfulness of the physical movements of the breath is the first emphasis in any concentration practice. The feelings group is ***becoming sensitive to rapture and joy in meditation***and then calming or letting go of rapture. The third group is the mind group – becoming aware of the mind, gladdening the mind, steadying the mind, and liberating the mind. (See “Breath by Breath” by Larry Rosenberg. This is a book Clouds in Water studied several years ago).

The fourth group the wisdom group is very similar to Suzuki Roshi’s quote above.

From a Thich Nhat Hanh translation:

13. I am breathing in and observing the impermanent nature of all dharmas. I am breathing out and observing the impermanent nature of all dharmas. He practices like this.

14. I am breathing in and observing the fading of all dharmas. I am breathing out and observing the fading of all dharmas. She practices like this.

15. I am breathing in and observing liberation (cessation). I am breathing out and observing liberation (cessation). He practices like this.

16. I am breathing in and observing letting go (relinquishment). I am breathing out and observing letting go (relinquishment). She practices like this.

This sutra demonstrates how the breath can take you all the way to the deepest realizations. The breath often is used as the first object of concentration. But it also can practiced as a complete teaching which leads to insight.

In Larry Rosenberg’s book, he writes about Buddhadasa’s approach to breath practice and its use for going all the way to realization. He writes:

“ When we got to the thirteenth contemplation – which concerns impermanence, this is where real vipassana begins – he said that Anapanasati was one of the simplest and most effective means for realizing emptiness.” 

Buddhadasa said: “There is no question that breathing is taking place. Can you see that there is no breather to be found anywhere? The body is empty, the breath is empty and you are empty.” 

Perhaps this is where Zen and Vipassana meet. Where the Mahayana and the Theravada come to the same conclusion.

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.http://www.judithragir.org/2014/01/exhaling-and-dissolving/

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CBD Anti-inflammatory, does not make you “high”


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CBD from CV SCIENCES Las Vegas, NV, is top rated by Consumer Labs. They sell CBD spray, oil, capsules, and softgels. The soft gels contain 5mg of hemp-derived CBDA/CBD oil per serving that includes terpenes, phytocannabinoids, fatty acids. Capsules contain 10 or 15 mg CBD are “made using our Total Plant Complex” that includes terpenes, phytocannabinoids, plant sterols, fatty acids.

One patient says the softgel is small, easy to swallow. “PlusCBD Oil Raw Softgels offer the fullest spectrum of naturally occurring hemp co-factors and contain 5mg of hemp-derived CBDA/CBD oil per serving.” [6.2 mg consumers labs say, tho bottle says 10 mg]

CWHemp in Boulder, CO, sells CBD oil and capsules. One patient who had 3 different pain conditions, each one disabling, severe, found it far better than CBD tried in 3 different states.

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One patient, A, has several conditions responding to CBD, discussed below.

TINNITUS:

She has suffered many years of tinnitus.

Soon after starting CBD, the tinnitus is now down to where she is just barely able to hear it. “It was driving me crazy: clicking, grinding, hissing, whiny, scraping like pieces of sandpaper being scraped together. I thought I’m going to go crazy. Now I can barely hear a hiss at all on left, and on the right very very low hardly discernible hiss. It’s like a miracle.”  Taking 1 twice daily, maybe have been taking them for 2 weeks, it’s amazing to me.”

Pains are 80% better:

Stiffness in hands, osteoarthritis arthritis pain in knuckles

 
70% relief left shoulder had been barely able to pick up the shoulder due to bone on bone osteoarthritis. Not frozen shoulder but the pain mimicked frozen shoulder, pseudo-frozen. Markedly better.


Anxiety:

Lifelong anxiety disorder has been helped to a degree, allowed drop in Xanax down to 3.0 mg/day from 3.5 mg total daily dose of Xanax she was taking since 1990. And dropped dose within the first week on 12 mg CBD dose, able to leave out the 2 pm Xanax. 


Had been using 2  of the 12 mg capsules from Leafly initially.


Vertigo due to BPPV, very severe:

25% improved, can roll over in bed now without feeling like flying off the bed. Helped balance related to the vertigo. The tinnitus had made the vertigo worse, so lessening of tinnitus has lessened the vertigo. Helped the balance, not a lot, but since vertigo is diminished, balance is better. 


“THC gives me more trouble than the CBD because I know I am not going to have a paranoid attack on CBD.  I’ve now lost my desire to smoke marijuana for relief. There is no change yet in depression, but during SAD [Seasonal Affective Disorder] and weeks of grey weather, I can’t tell.”

BAM, the devastating bile acid malabsorption:

No change yet. I have been manipulating diet to get results I need, now fairly good control by taking more water. Not having the horrible bile burn in lower abdomen, none in days. I’m not sure why yet. Water intake, I can’t even tell because I’m so sporadic. If I could get into me minimum 4 full glasses a day, I probably could control the constipation part. I’d rather deal with that than the diarrhea which is debilitating.” 

Ear Pressure:

JG no longer needs to be taking ibuprofen to treat PRESSURE in ear. It felt like the tubes were full of fluid and that pressure from the tubes was having a vacuum type effect on the eardrum itself.  He’s been to every ENT at Rush Memorial, next will see ENT at Loyola. It was distracting and uncomfortable, made him miserable, frustrated and did not want to take the medication because he was concerned about NSAID adverse effect on the heart. Was taking Ibuprofen every few hours, now no longer needed. This pressure has been disabling for years.

 
He is taking CBD 12mg/day, now will start taking 18-19 mg.
This is profound. 

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please ignore the ads below. They are not from me.

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Oxytocin for Pain, Treatment Resistant Depression and Bipolar Disorder


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Recent publications on Oxytocin are listed below. It is a very effective hormone made by the brain. It is NOT the opioid oxycodone and NOT oxycontin.

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Use search function top left above photo to see previous postings on oxytocin since 2013. It can be extremely important in the treatment of intractable pain, treatment resistant depression, bipolar disorder or anxiety.

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Once you titrate to the proper dose for each person —from 10 to 100 u’s, relief is quite astonishing, with rapid onset in a few minutes when given under the tongue – only after reaching that person’s dose, simple, without side effects. May use as needed 3 or 4 times per day. There is no withdrawal.

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Avoid use if polycystic ovary syndrome (PCOS). 

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Oxytocin must be made by a compounding pharmacy. Healthcare insurance refuses to reimburse for any compounded medications though they are far less expensive even than gabapentin that fails to help so many with pain, and oxytocin is far more effective. 

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Every time you hug someone, you are giving each other oxytocin. When your dog and you stare at each other, oxytocin is being stimulated. Having discussed that with one of my patients, he came back one month later to say he and his wife had fallen in love again after almost 50 years of marriage because they’ve been hugging every day: hugs stimulate oxytocin. 

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Behavioral effects of oxytocin are highly context- and person-dependent. You are not going to fall in love with someone you do not like. 

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Rash, JA, et al: Oxytocin & Pain, A Systematic Review & Synthesis of Findings. Clin J Pain 30(5):453-462, May 2014.

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Xin Q et al: The Analgesic Effects of Oxytocin in the Peripheral and Central Nervous System. Neurochemistry Intl 103:57-64, 2017.

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Paloyelis Y et al: The Analgesic Effect of Oxytocin in Humans: A double-blind, placebo-controlled, cross-over study using laser-evoked potentials. 

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MacDonald K, Feifel D. Oxytocin’s role in anxiety: a critical appraisal. Brain Res 2014; 1580: 22–56.

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Churchland PPS, Winkielman P. Modulating social behavior with oxytocin: how does it work? What does it mean? Horm Behav 2012; 61: 392–399.

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Bethlehem, R A I  et al: Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women, Translational Psychiatry, 2017, 7, 4, e1099 ********excellent********

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Cannabis That Can Stop the Munchies? What is THCV?


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MEDICAL MARIJUANA

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Cannabis is legal in California for adult use as of January 1, 2018. This may be helpful to someone you know. It is a most important drug. Below you can find a few pointers that are basic to understanding what strains to try. Distributors are swamped with ten times as many buyers as last week, prices are doubled, taxes are very high, it is very expensive and you will need to test many strains before you find what works for you without making you stupid with euphoria that lasts 12 hours. Do be warned of turning the body into sofa-size obesity overnight. Munchies occur with high THC strains. To discuss below how to avoid that torture and still relieve pain or muscle spasm.

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Horvath et al at Yale in 2015 found cannabis stimulates hunger and arousal in hypothalamic neurons. Here’s the YaleNews on the multi-authored work.

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Horvath is the Jean and David W. Wallace Professor of Neurobiology and of Obstetrics, Gynecology, and Reproductive Sciences, director of the Yale Program in Cell Signaling and Neurobiology of Metabolism, and chair of the Section of Comparative Medicine.

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To orient you in the quote below, cannabinoid receptor 1 (CB1R) is one of the two known cannabinoid receptors in the brain. Others are located outside brain, throughout the body.

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“The Pomc gene encodes both the anorexigenic peptide α-melanocyte-stimulating hormone, and the opioid peptide β-endorphin. Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety. Cannabinoid receptor 1 (CB1R) is critical for the central regulation of food intake. CB1R activation selectively increases β-endorphin but not α-melanocyte-stimulating hormone release in the hypothalamus, and systemic or hypothalamic administration of the opioid receptor antagonist naloxone blocks acute CB1R-induced feeding.

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Interesting. Low dose naltrexone, which is essentially long acting naloxone, may block munchies in humans? At what dose? Please comment if you take naltrexone 4.5 mg or 15 mg (anti-inflammatory doses) or 28 mg (weight loss dose) or 50 mg and above doses of naltrexone (high doses for addiction).

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One strain that is better at stopping or reducing the munchies, and that is believed due to a cannabinoid in the strain called THCV. You can always do a search for THCV.

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Cannabis is one of the few medications that can relieve some of the worst side effects of opioid withdrawal. Many patients find they need to use fewer opioid pills for pain or can stop them altogether; they need to use fewer muscle relaxants; and they can eat or sleep better if they use cannabis. Once cannabis became legal, many alcoholics were able to give up alcohol because their first preference is cannabis.

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Get a low cost recommendation for medical marijuana in minutes at home from your mobile phone. The best source for recommendation is : HelloMD.

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Cannabis may be legal in all states once tobacco companies toss some money at Congress. Could cannabis be related to the vow of Phillip Morris and a wave of big tobacco companies to stop selling cigarettes this year?

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It is dreadfully expensive and heavily taxed. All states should adopt New Mexico’s law that allows healthcare insurers to reimburse patients who have paid for medicinal cannabis. Voters…

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Cannabis is made by the body and the brain makes two of the endogenous cannabinoids. If is highly anti-inflammatory, and profoundly important mainly in the immune system but also in bone turnover. You have more cannabinoid receptors in your body than any other kind. It is as old as sponges, an ancient medicine.

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A WORTHY READ

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Mr. X – by Carl Sagan who describes his experience with marijuana at length and used it creatively for decades opening his brain to experiences he was otherwise not oriented to at all.

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MUNCHIES

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Fear the munchies. Cannabis, medical marijuana, can cause the munchies, an overwhelming desire to eat nonstop, usually all the most high calorie things your desperately fevered brain can dream of cramming in.

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Certain strains of cannabis can be life saving for those who have loss of appetite from conditions such as cancer, HIV/AIDS, depression, inflammatory conditions, etc. But the munchies can be disastrous when you cannot afford to gain weight due to pain or disability or simply wish to develop an important standard to maintain best health which means good lean body weight. The best way to reduce inflammation is to avoid obesity, avoid sugar, avoid diabetes, heart attacks, strokes. Remember inflammation is the root cause of 90% of the conditions we die of: diabetes, cancers, Alzheimer’s, Parkinson’s, autoimmune disease, atherosclerosis, etc.

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Those with an eating disorder should scrupulously avoid those strains that are highly rated for helping anorexia, loss of appetite.

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CHOOSE STRAINS THAT STOP THE MUNCHIES

STRAINS WITH HIGH THCV  OR HIGH CBD 

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If needing high THC for pain or appetite, for example, then a strain with high THC and high THCV is Durban Poison. Read in detail about strains on leafy.com using the search function and it will find dispensaries in your area.

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If low THC is all you need, then Leafly discusses high CBD strains with low THC currently available. Google it or ask the dispensary.

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I am not going to do more than mention these three cannabinoids: THC, CBD, THCV. You can google them but do glance at my outdated 2009 cannabis website – CBD has vastly changed since then, available even at farmer’s markets and nutrition departments of groceries.

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The cannabis plant has 400 chemicals of which about 86 are known cannabinoids but we focus on just a few and hybrids have been bred to display many qualities and various percentages of cannabinoids.

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THC

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THC, tetrahydrocannabinol, can cause euphoria and is the principal psychoactive ingredient useful for pain, depression, appetite, multiple sclerosis, fatigue, stress, and many conditions including just to have fun, be giggly or creative. For the California Medical Board, a strain with 18% THC is considered high, but some strains such as Holy Grail have 27% or more THC. Some strains are noted for causing more anxiety or paranoia due to THC content. It is widely said THC is necessary for pain relief but… see CBD below.

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CBD

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CBD, cannabidiol, a non-psychoactive cannabidiol that blocks the psychoactive component of THC so that you may be able to mix with THC in order to use a stronger dose of THC for the underlying condition —  find your best ratio of CBD to THC. Or use 100% CBD. Among strains of flower sold at dispensary, I’m not sure what % CBD

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Some people are highly sensitive to THC (paranoia, panic attacks, anxiety) and cannot use any THC or only very tiny amounts of THC with higher percentage CBD.

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Some use pure 100% CBD which is said to be useful for Crohn’s Disease, PTSD, multiple sclerosis and certain seizure disorders, the severe childhood Dravet Syndrome. There is a recent single report of an adult who failed all anticonvulsants and responded to CBD alone. I have seen a patient with depression after 2 years of severe disability from 4 major chronic pain conditions, surprisingly all pain 100% relieved by CBD. It is widely said that THC is essential for pain relief but for this case not needed.

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Some dispensaries will mix liquid CBD:THC in ratios of 15mg/mL CBD to 0.1 mg/mL CBD all the way up to ratio of 15:15 or more. Use topically, under tongue or swallow. One patient dilutes and uses topically. Very expensive!!! It is the only thing helping his extremely painful autoimmune neuropathy.

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THCV

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Leafly discusses ten strains that will not make you (as) hungry

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After discussing high CBD strains, then turn to high THCV:

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High THCV Sativa Strains

“By now you know what THC and CBD is, but you may not be familiar with the less ubiquitous THCV, a related chemical that suppresses appetite. While most strains on the market today tend to test anywhere between 10-20% THC, what’s considered a high THCV content might only hit a high-water mark of 5%. THCV tends to be more abundant in sativa strains, and it’s possible you’ve noticed that sativas tend to provoke hunger less than indica strains. The unique metabolic effects of THCV even have researchers considering its utility in treating obesity and diabetes.”

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Durban Poison is the name of the strain with highest THC and THCV, and a good profile detailed on Leafly: Maximal effect is Energetic > happy > uplifted >> focused >> euphoric. Not everyone may have all these effects.

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Always check Leafly’s negatives for each strain and look at the bar graphs — how severe are the side effects? Note that always worst is dry mouth. Half as bad are dry eyes for this strain – at least not as bad as dry mouth; and much lower in incidence is dizzy, anxious, paranoid. Overall a very good profile for a high THC strain.

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RISKS

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Note, those with Sjogren’s Syndrome who have dry eyes are at risk for corneal transplants and who have dry mouth are at risk for all teeth crumbling, so choose and treat accordingly.

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Cannabis can increase pulse and blood pressure which can be a risk of heart attack and stroke for any age. It is especially likely if you are naive to the drug, i.e. have never used it or have not introduced it to your system for decades. Check blood pressure and pulse before use and after you feel the peak effect.

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The youngest person I found on the internet who died of heart attack caused by cannabis was a healthy 17 year old male, possibly a false report, but cardiac arrhythmias can be fatal and there are undiagnosed cardiac conditions in young athletes who may be likely to use cannabis.

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Cannabis can interfere with memory.

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The adolescent developing brain may be vulnerable to harmful effects.

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HOW TO USE IT

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Vaporize it. Avoid 4 toxins. Rapid onset, short duration of effect.

If smoking, you will inhale 4 major toxins.

Use under tongue or topically on skin.

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If you swallow cannabis, you will not feel effect for 90 to 120 minutes so allow 2 hours before you add more or you may seriously overdose. Duration of effect may be 4 to 12 hours or more – overdosing can last days.

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5 mg oral THC may be too much for a starter dose for some people, but may be average for many, and some may need 10 mg. But heavy users need far, far more: TOLERANCE DEVELOPS!!! Money down the drain. Use only as much as you need or you will develop tolerance and require more frequent and higher and higher doses to reach same effect. That can be unaffordable for the average middle class person. 

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And yes, it may appear in urine for 30 to 60 days, possibly more.

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Cannabis is still a schedule I drug. The Emperor has no clothes. Do not take it onto planes or attempt to mail it.

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Do read more about it on my cannabis website linked above. It is a drug. You will benefit from learning how to use it.

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The material on this site is for informational purposes only.

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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

~~~~~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please IGNORE THE ADS BELOW. They are not from me.

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Got no business feelin’ down – Music


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I got no business feeling down. Music can be fun. Turn on the best. Find your self. Have some fun here. Stop that freekin gloom.

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It will take some work. Words have power.

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Music

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Y’all know the Abyssinian Baptist Gospel Choir don’t you? What do you think they’re singing about? There’s better ways to be happy than to allow the mind to sink back down to the world. It’s the spirit!

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The Beatles, “I Wanna Hold Your Hand. And when I touch You, I feel happy inside. It’s such a feelin that my love I can’t hide. Yeah you, you’ve got that something, I think you’ll understand.”

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Whatever that Infinite is, that Bliss, the only way to know It is to BE It. You already are. You, I, we are infinite. So make happy. You can’t destroy the ones you hate, we gotta love em. They are us. They are god too. You cannot divide infinite by 2, it’s still 2. It’s all Infinite. Just run from the danger gods.

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How to understand this? “The seeds of love I sow, ” Led Zeppelin, Physical Graffiti,”Let music be your master. Will you heed the Master’s call?

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Ain’t no Judas. It’s all Love. Every last one. You don’t have to worry. It’s a movie. You are infinite, remember? It’s real and it’s a movie all at the same time. Step away for a bit and check out these lyrics I never heard til now.

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Love the Great Spirit, the Infinite, the Absolute, Truth, Consciousness. The world pulls us down. It succeeds! I got no business allowing that. I can do better. Just how to do that is this.

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Led Zeppelin, Physical Graffiti

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Houses Of The Holy  
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Let me take you to the movies. Can I take you to the show
Let me be yours ever truly. Can I make your garden grow
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From the houses of the holy, we can watch the white doves go
From the door comes Satan’s daughter, and it only goes to show. You know
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There’s an angel on my shoulder, In my hand a sword of gold
Let me wander in your garden. And the seeds of love I’ll sow. You know
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So the world is spinning faster. Are you dizzy when you’re stoned
Let the music be your master. Will you heed the master’s call
Oh… Satan and man
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Said there ain’t no use in cryin’ ‘Cause it’ll only drive you mad
Does it hurt to hear him lyin’? Was this the only world you had? oh-oh
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So let me take you, take you to the movie. Can I take you, baby, to the show
Why don’t you let me be yours ever truly.
Can I make your garden grow

you know.

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Kashmir
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Oh, let the sun beat down upon my face
And stars fill my dream
I’m a traveller of both time and space
To be where I have been
To sit with elders of the gentle race
This world has seldom seen
They talk of days for which they sit and wait
All will be revealed
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Talk in song from tongues of lilting grace
Sounds caress my ear
And not a word I heard could I relate
The story was quite clear.
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Ooh, baby, I been blind
Oh, yeah, mama, there ain’t no denyin’
Oh, ooh yes, I been blind
Mama, mama, ain’t no denyin’, no denyin’
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All I see turns to brown
As the sun burns the ground
And my eyes fill with sand
As I scan this razor line
Can I find, can I find where I’ve been
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Oh, pilot of the storm who leaves no trace
Like sorts inside a dream
Leave the path that led me to that place
Yellow desert stream
Like Shangri-la beneath the summer moon
I will return again
As the dust that floats finds you
Will move and search Kashmir
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Oh, father of the four winds fill my sails
Cross the sea of years
With no provision but an open face
Along the straits of fear
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Oh, when I want, when I’m on my way, yeah
And my feet wear my fickle way to stay
Ooh, yeah yeah, ooh, yeah yeah, but I’m down
Ooh, yeah yeah, ooh, yeah yeah, but I’m down, so down
Ooh, my baby, oh, my baby
Let me take you there
Come on, oh let me take you there
Let me take you there back to top
In The Light
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And if you feel that you can’t go on
And your will’s sinking low
Just believe and you can’t go wrong
In the light you will find the road
You’ll find the road
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Hey, ooh, did you ever believe
That I could leave you standin’ out in the cold
Hey, baby, I know how it feels
‘Cause I have slipped through
To the very depths of my soul
Oh, baby, I just want to show you what I’d give you
In case you ever been on the road
Now, listen, oh, as I was and would do for you, too
Honey, as you would do for me
I would share your load, let me share load
Ooh, let me share you load
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And if you feel that you can’t go on
In th light you will find the road
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Hey, oh the winds of change may blow around you
But that will always be so
Oh wo, when love is pain it can devour you
If you are ever alone
I’ll share your load, I will share your load
Baby, let me, oh let me, in the light
Everybody needs a light, oh yeah, oh baby
Everybody, everybody, everybody sure ’nuff they do
Light, light, light, in the light (Repeat)

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Be the witness. Watch the movie, don’t sink into it. It’s only the body. Step away for a few minutes. Be aware of love and consciousness of spirit. Expand consciousness as often as you can. Fill the heart with love. Practice this. Meditate from the heart. We get stuck but sometimes we need to break out some music. You are not the body or the mind. You don’t think God is fun? Infinite is more fun than imaginable, they say. You may have evolved in taste for music, Infinite Bliss has infinitely better, sages say.

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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This site is not for email and not for appointments.

If you wish an appointment, please telephone the office to schedule.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Please ignore the ads below. They are not from me.

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Ketamine Nasal Spray for Major Depression – The First Randomized Controlled Trial


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A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

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Psychiatrists from Mt. Sinai in New York this month have published the first randomized controlled trial of intranasal ketamine showing it is safe, well tolerated, and rapidly effective in treating symptoms of depression in persons with Major Depressive Disorder.

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This is a small study of 18 patients with treatment resistant depression showing a significant antidepressant effect occurred as early as 40 minutes in some. 44% responded after 24 hours compared to 6% placebo. Ketamine was significantly different from placebo at 40 minutes, 240 minutes, and 48 hours, but not separable from placebo at 72 hours or 7 days thought they were still better. And ketamine was significant at improving anxiety symptoms at 24 hours. There were no clinically significant changes in heart rate or blood pressure and all changes resolved in four hours. “No serious adverse events occurred.”

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“Intranasal ketamine was well tolerated with only very minimal increases in dissociation, psychosis-like symptoms or hemodynamic parameters.” They felt these very minimal behavioral side effects and insignificant changes in blood pressure and pulse were consistent with the lower blood levels of ketamine compared to the higher doses used in studies of IV ketamine. Bioavailability via intranasal route is reported to range from 25% to 50%.

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Their sample had an average of 4.1 ± 3.9 treatment failures, compared to 5.7 and 5.1 in previous studies – those required a minimum of 2 to 3 treatment failures to enroll. Other clinical characteristics did not differ including “duration of illness, length of current depressive episode, and history of ECT.” They allowed ongoing treatment of psychotropic medication.

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They chose a 50 mg dose based on a previous study and on the dose used in persons with a chronic pain disorder (Daniel Carr, et al 2004). It is a lower dose than the 0.5 mg/kg dosage commonly given intravenously. They point out one limitation of the study was the use of the single dose and a standardized protocol, which did not allow them to study optimal dosing. Future study is needed to address optimal dosing, relapse prevention and scheduling of treatment.

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The minimal side effects shown in their study correlates well with my experience. I find the effective dose of ketamine is idiosyncratic. That means it is unpredictable and specific only to that individual. Large males may need only the smallest dose, and tiny elderly females may require far higher doses. That may account for the higher response rate that I believe I am seeing, however, I have not tracked percentage of responders. I have not seen toxicity in years of prescribing either for intractable pain or treatment resistant depression. Importantly, in my opinion, relapse prevention must address not only different neurotransmitters but also neuroinflammation, pro-inflammatory cytokines.

 

 

 

 

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Oxytocin, Astrocytes, Modification of Amygdala Circuits and Pain – IASP Early Research Career Grant Report


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As a physician who prescribes Oxytocin [OT] and sees profound relief of many forms of intractable pain and/or relief of treatment refractory Major Depressive Disorder or Anxiety and Panic Disorder, this research on mechanisms is deeply meaningful and long awaited. Oxytocin is a hormone made in the brain, but also in the heart and other organs in women and men. It is rare to find work on glia and oxytocin.

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Today the International Association for Study of Pain announced the final report from their 2012 Early Research Career Grant:

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“Dr. Alexander Charlet of the Centre National de la Recherche Scientifique (CNRS) in Strasbourg, France, has submitted his final report for his project “Involvement of astrocytes in the endogenous oxytocin modification of amygdala microcircuits….”

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“Dr. Charlet’s project focuses on the functional consequences of endogenous OT release in amygdala microcircuits on nociception and pain. In addition, he aims to decipher the precise mechanism, cellular and molecular, by which OT exerts its action. Thus, the purposes of his project are to characterize in vivo and in vitro the effects of endogenous OT in the amygdala on pain-related symptoms….

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.….”In addition, he was surprised to discover that perceptions of his project’s importance grew once it was awarded and triggered future collaborations: a Marie Curie European Action Career Integration Grant and the French Initiative d’Excellence Attractivity.”

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“As a result, Dr. Charlet also received two major personal prizes: an award from Swiss Society for Biological Psychiatry in 2012 and award from the French Académie nationale de medicine with the prestigious Albert Sézary price in 2013. Finally, he has been recruited as a neurosciences permanent researcher by the CNRS and recently opened his independent lab.”

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Ketamine Inhaler – Bipolar Child NPR – Review of Ketamine for Depression


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NPR reported yesterday on the beneficial effects of ketamine for depression, this time reporting on a ketamine inhaler prescribed by Demitri Papolos, MD.

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Dr. Papolos is Associate Professor of Clinical Psychiatry at the Albert Einstein College of Medicine and Director of Research of the Juvenile Bipolar Research Foundation.

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He “is one of a handful of psychiatrists in the world who began to see and to speak out about the possible deleterious effects of antidepressants and stimulants in the population of children within the bipolar spectrum.”

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This NPR report described a syndrome Dr. Papolos has identified of Bipolar children & adolescents consumed by fear. They described a boy who had extreme attacks of rage for decades, and horrific violent nightmares.

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The boy had attempted suicide at age 5. He was hospitalized in a psychiatric unit at age 12 and strapped down in a padded room, terrified. He failed many medications for years, some made him worse, and he was literally never able to complete a meal at table with the family without flying off in a rage or someone leaving.

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in 2010, the boy tried Dr. “Papolos’ ketamine treatment. He says he’ll remember the day for the rest of his life. ‘I think we did two puffs, and I remember I sat up and I just started laughing,’ he says. Then his mother picks up the story: ‘You said you had an internal feeling of calm that you had never had before in your life. And when we came home that night, that was the first night that we ever all had dinner at the table without somebody leaving.'”

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This boy, George McCann, now at age 22 is finally able to begin a more normal life. He needs the medication only every third day. “Papolos has treated about 60 young people with ketamine so far and says all but two have had dramatic responses.”

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“The number of patients treated so far is small, and the approach is so new it hasn’t been tested by other researchers yet. Papolos says he’s hoping a study he published late last year will help persuade other researchers to try the drug on other children.”

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“In the meantime, George McCann continues to inhale a prescribed dose of ketamine every third day. The fear and anger that once dominated his life are gone, he says, adding that his mind is free now to work….”

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The relief with ketamine from the prison of mood disorders is deeply important. Severe mood disorders such as Major Depression and Bipolar Disorder can destroy the lives of patients and their loved ones. At worst, they can be lethal.

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A review of published cases of intravenous ketamine for depression asks : “Ketamine for depression: where do we go from here?

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I think the answer is we need to simplify the method of treatment using inhaled ketamine and begin to give their lives back to the patients we see. It is one of the safest medications I have ever prescribed. It does not cause weight gain or loss. It does not cause sexual dysfunction. And although it may increase sedation when used in combination with other sedating medications, at the low doses needed to treat mood disorders, I do not see ketamine interfere with other medication.

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Ketamine can relieve depression from one second to the next. And this young man needs the medication every third day. Is that too much to ask to gain a life?

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The material on this site is for informational purposes only, and is not a substitute for

medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Ketamine Rapidly Relieves Depression by Restoring Brain Connections


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This research is one of the most dramatic findings in the field of depression and mood disorders. It was published in Science by researchers from Yale and the National Institute of Mental Health, discussed by PBS here.

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The speed with which ketamine can relieve major depression is deeply moving to witness. In my experience prescribing nasal ketamine it works almost 100% of the time. I have discussed ketamine and previous publications on it for Major Depression and PTSD. It is also effective for suicidal and bipolar depression patients.

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Ronald S. Duman, PhD, the lead scientist, reviews his group’s research in this 2011 video:

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Stress and depression leads to structural changes in the brain and these structural changes are reversible.

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Depression affects 17% of the population, almost one in five of the population. Only one third of patients are effectively treated by existing antidepressants, even after many weeks. Nerve growth factors, in particular BDNF, are decreased by stress, with a very significant loss in depressed patients. BDNF produces antidepressant behavior in rodent models of depression.

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BDNF is important for influencing the survival and function of neurons.

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There are certain neurogenic zones in the brain that produce new neurons. Stress decreases the number of new neurons. Chronic antidepressant use increases the numbers and proliferation of these new neurons. Antidepressant treatment increases neurogenesis and this is dependent upon BDNF, this neurotrophic factor.

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[His slide shows] Exercise, Prozac, ECT, antipsychotics, antidepressants increase neurogenesis.

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Not only are there more synapses made by ketamine, but they are a larger size which is indicative of ones that are more functionally connected. Antidepressants take many weeks. A single dose of ketamine rapidly reverses depressive behaviors and loss of connections and completely reverses the decrements that had occurred over several weeks.

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In suicidal patients given ketamine at Yale in the Emergency Room, within a matter of hours, the suicidality is completely reversed. These people are better for weeks after a single dose of ketamine treatment. [emphasis mine]

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Therapeutically ketamine is even more rapidly acting than ECT.

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Ketamine increases BDNF. But research shows its effects are blocked in mice that are deficient in BDNF. Riluzole also influences BDNF, but the side effect profile is so serious that I would not consider prescribing it without more data on safety.

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Safety concerns are often raised in publications regarding chronic ketamine use. Most of my patients have no side effects at all. It is one of the safest medications we have and only a small percentage experience transient side effects. The favorable side effect profile, simplicity and low cost is key. The results for nasal ketamine are not 100%, neither is IV ketamine, but I have patients who respond to nasal spray when they failed IV ketamine. More importantly, they can carry it in their pocket and use as needed.

 

My experience prescribing ketamine goes back almost to the year 2000 for persons with chronic pain who have used ketamine several times daily, and since Spring 2012 for Major Depression. Its effect for depression lasts longer than for chronic intractable pain where it is short lasting. In the past, I prescribed it orally, by mouth, but since late 2011 I have prescribed it in a nasal spray and that form works for depression.

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The neuroprotective action of ketamine has been published since at least 1988.

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Patients can use nasal ketamine as needed. Schedules vary, everyone is different. It is short acting, but it does not stop working.

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However, the use of other adjuvants, such as glial modulators, in treatment of depression is essential to understand, and is now work in progress. The role of inflammation and glia in the pathogenesis of depression has been well established since 2000, and discussed here.

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Does ketamine also restore brain connections in patients with chronic pain? Chronic pain and major depression both lead to brain atrophy and memory loss. Both cause the same imbalance in glial cytokines. Both may respond to glial modulators, e.g. low dose naltrexone among others that have worked in some patients.

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“The original link between ketamine and relief of depression was made at the Connecticut Mental Health Center in New Haven by John Krystal, chair of the department of psychiatry at Yale, and Dennis Charney, now dean of Mt. Sinai School of Medicine, who helped launch clinical trials of ketamine while at the National Institute of Mental Health,” reported by Yale  here.

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I hope to add new approaches to treatment of anxiety that has failed to respond to other interventions.

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The material on this site is for informational purposes only, and is not a substitute

 for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Ketamine Intranasal for Rapid Relief of Pain and Depression


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Poorly managed pain can evolve into chronic disease of the nervous system

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Ketamine is an important analgesic, more important than opioids. It can dramatically reduce pain, and rapidly relieve depression and PTSD.  Please read my earlier posts here and here. And the NPR report here just after I posted this (skip to their last section). Yes, it is FDA approved and legal. One woman said:

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 ‘It was almost immediate, the sense of calmness and relaxation.

‘No more fogginess. No more heaviness. I feel like I’m a clean slate right now. I want to go home and see friends or, you know, go to the grocery store and cook the family dinner.’

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NPR again reports ketamine’s rapid relief of depression. A 28 year old man whose refractory depression began at age 15, after ketamine, says:

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‘I Wanted To Live Life’

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Stephens himself has vivid memories of the day he got ketamine. It was a Monday morning and he woke up feeling really bad, he says. His mood was still dark when doctors put in an IV and delivered the drug.”Monday afternoon I felt like a completely different person,” he says. “I woke up Tuesday morning and I said, ‘Wow, there’s stuff I want to do today.’ And I woke up Wednesday morning and Thursday morning and I actually wanted to do things. I wanted to live life.”.
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Since then, they treated him with Riluzole that is FDA approved for ALS and has one of the dirtiest side effect profiles I have ever seen in medicine with serious organ toxicity. Ketamine rarely causes mild transient side effects, usually none. It appears the concern is how ketamine is used on the street with potential for abuse. I do not see ketamine abuse in my patients, some of whom are on opioids for pain or Valium family medicines from their psychiatrist. All of those have a greater potential for abuse, also not occurring in my patients. Pain and/or depression can lead to suicide.
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About 18 months ago, researchers at Yale found a possible explanation for ketamine’s effectiveness. It seems to affect the glutamate system in a way that causes brain cells to form new connections.
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Researchers have long suspected that stress and depression weaken some connections among brain cells. Ketamine appears to reverse the process.

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It would be of interest to see a case report of the bladder problems they mention. Is this in a single drug addict who used many unknown medications on the street? Several physicians have infused IV ketamine for persons with pain for many years, in far higher doses than I prescribe, with no report of any but transient minor symptoms.

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David Barsook’s 2009 review, reference below, describes changes that cause memory loss and brain atrophy with chronic pain, in particular, Complex Regional Pain Syndrome (CRPS), and they also occur with chronic depression:

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With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death.

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Brain atrophy and memory loss has also been shown in chronic low back pain as well as in chronic depression.

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Barriers to management of chronic pain are many:

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Although opioids are effective for acute pain, effective treatment of chronic pain is often daunting, particularly neuropathic pain.

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Opioids have been shown to create pain causing imbalance in the glial cytokines that favor pain rather than relief of pain. Opioids carry the risk of opioid-induced hyperalgesia which is a severe pain sensitivity. They affect the brain and endocrine system. Opioids may fail to offer significant relief, fail to improve function, and risk misuse, abuse, diversion and death. Their costs are astronomic, insurance coverage is increasingly limited, the potential for complications may be life threatening in a hectic medical setting, side effects can be lethal, lack of physician training in use of opioids and alternatives to pain control lead to increasing deaths, addiction and diversion. It has become a national emergency and a trillion dollar war on drugs.

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Complications can be greatly reduced through use of a scrupulous history and physical examination, but reimbursement is directly proportional to the shortest time spent with a patient. Will that help assessment and care?

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Individuals may have dramatically different responses to opioid therapy; some may not tolerate any, and relief must be balanced with side effects that increase as the dose increases. Patient status may change and require IV, rectal or tube delivery instead of oral formulas; drug-drug interactions may require rapid changes, and disease of kidney, liver or brain may require modifications or stopping altogether. They may increase risk of falls and cause central sleep apnea with drop in oxygen because the brain fails to give a signal to breathe.

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Chronic pain can lead to loss of sleep, hopelessness, depression, anger and other mood disorders such as panic, anxiety, hypochondriasis and post traumatic stress disorder [PTSD]. Treatment of mood disorders are shown to profoundly reduce pain perception and/or ability to cope with pain.

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Ketamine is anti-inflammatory and can reduce the need for opioid use, thus reducing the pain and side effects caused by opioids.

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Nasal ketamine is more effective than oral ketamine for pain relief; oral dosing has no effect on depression.

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Nasal delivery of ketamine is now possible due to advances in metered nasal sprayers that deliver a precise dose. No needle is required, no IV access, no travel to a specialist needed.

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You can carry pain relief with you and use it as directed when it is needed.

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Ketamine is an NMDA antagonist: it antagonizes the NMDA receptor which plays a profound role in pain systems and centralization of pain.

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Ketamine is neuroprotective and it can help other disease states as noted by Barsook, 2009:

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Besides improvement in pain, “there may be lessons from other diseases that affect the brain; it is noteworthy that acute ketamine doses seem to reverse depression and ketamine decreased prevalence of post-traumatic stress disorder (PTSD) in soldiers receiving ketamine during their surgery for treatment of their burns. In addition ketamine attenuates post-operative cognitive dysfunction following cardiac surgery that has been known to produce significant changes in cognition. [emphasis mine] The data suggest that the drug can alter or prevent other conditions based on its NMDAR activity where other drugs NMDA receptor antagonists are perhaps not as effective in these or pain conditions. Lastly, NMDA antagonists have been used in degenerative disease (and pain may be considered a degenerative disease as defined by loss of gray matter volume, see above) with mixed effects perhaps relating to how they act on specific NMDA subtypes. Taken together, ketamine may act not only on sensory systems affecting pain intensity, but also on a constellation of brain regions that are involved in the pain phentype. [sic, phenotype]”

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Side Effects

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Ketamine is more frequently used in babies and children than in adults because high doses of ketamine can induce hallucinations in the adult. Importantly, it is used in high dose in adults for treatment of Complex Regional Pain Syndrome.

Low doses, cause little or no side effects in adults. If present, they are transient and often resolve in 20 minutes. Patient who respond to ketamine report good acceptance as they find the relief of pain and/or depression far outweighs any short term minimal discomfort.

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Pain care reform is urgently needed.

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Research funding for pain is less than half of one percent of the NIH budget. More research is needed, but research on low dose ketamine for treatment of pain and depression has gone on for twenty years.

The public health crisis of untreated pain, which often results in disability, parallels the country’s struggle to halt the cost of health care. The longer a person remains with untreated pain, the less likely they are to return to work or to be employable.

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Conclusion

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Pain control requires urgent attention. It is past time to put into practice the use of this valuable medication so people can get on with life instead of being mired in chronic pain that for many risks suicide and ensures continuing decades of disability. Academic studies are usually limited by defining a predetermined dose rather than clinically titrating to effect. Thus no surprise, they find no effect as every patient will have no response until they reach their dose. And that dose, in my experience, falls into a bell shaped curve. One size does not fit all. Some respond at very low dose, others require much more, and the majority fall between.

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In my experience prescribing ketamine for ten years, only a rare person has problems. Almost all find it has returned function or significantly relieved pain. Some have been able to entirely eliminate opioids that did nothing for their pain for decades, though they dutifully returned to the MD every month to chronicle that pain. Pain continued to be rated ten on a scale of ten; patient always compliant despite side effects of constipation and often depression. My patients find the benefits of nasal ketamine far outweigh the relief of oral ketamine and at much lower doses with fewer side effects.

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Further, while the pain relief may be short lived, some find it gets better with repeat dosing, and relief of depression may last one to two weeks with a single dose.

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References

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http://www.wjgnet.com/1007-9327/10/1028.asp  Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats.

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CONCLUSION: Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-a and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.

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http://informahealthcare.com/doi/abs/10.1080/J354v16n03_03  Ketamine as an Analgesic Parenteral, Oral, Rectal, Subcutaneous, Transdermal and Intranasal Administration

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Ketamine is a parenteral anesthetic agent that provides analgesic activity at sub-anesthetic doses. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with opioid receptor activity. Controlled studies and case reports on ketamine demonstrate efficacy in neuropathic and nociceptive pain. Because ketamine is a phencyclidine analogue, it has some of the psychological adverse effects found with that hallucinogen, especially in adults. Therefore, ketamine is not routinely used as an anesthetic in adult patients. It is a frequently used veterinary anesthetic, and is used more frequently in children than in adults. The psychotomimetic effects have prompted the DEA to classify ketamine as a Schedule III Controlled Substance. A review of the literature documents the analgesic use of ketamine by anesthesiologists and pain specialists in patients who have been refractory to standard analgesic medication regimens. Most reports demonstrate no or mild psychotomimetic effects when ketamine is dosed at sub-anesthetic doses. Patients who respond to ketamine tend to demonstrate dramatic pain relief that obviates the desire to stop treatment due to psychotomimetic effects (including hallucinations and extracorporeal experiences). Ketamine is approved by the FDA for intravenous and intramuscular administration. Use of this drug by the oral, intranasal, transdermal, rectal, and subcutaneous routes has been reported with analgesic efficacy in treating nociceptive and neuropathic pain.
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http://www.ncbi.nlm.nih.gov/pubmed/15109503  Safety and efficacy of intranasal ketamine for the treatment of breakthrough pain in patients with chronic pain: a randomized, double-blind, placebo-controlled, crossover study  Daniel Carr, et al, 2004
Crossover, 20 patients. Ketamine reduced breakthrough pain within 10min of dosing, lasting up to 60min
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http://www.ncbi.nlm.nih.gov/pubmed/15288418  Safety and efficacy of intranasal ketamine in a mixed population with chronic pain
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The intranasal route for ketamine administration has been applied only for pain of dressing changes in a single case study (Kulbe, 1998). In this patient, oxycodone and acetaminophen were ineffective to control pain during burn dressing changes in a 96-year-old woman cared for at home. She tolerated the burn dressing changes after three intranasal sprays of 0.1 ml each, in rapid succession, each containing 5 mg ketamine (15 mg total) (Kulbe, 1998).
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http://www.acutepainjournal.com/article/S1366-0071%2807%2900167-2/abstract  Safety and efficacy of intranasal ketamine for acute postoperative pain
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Ketamine delivered intranasally was well tolerated. Statistically significant analgesia, superior to placebo, was observed with the highest dose tested, 50 mg, over a 3 h period. Rapid onset of analgesia was reported (<10 min), and meaningful pain relief was achieved within 15 min of the 50 mg dose. The majority of adverse events were mild/weak and transient. No untoward effects were observed on vital signs, pulse oximetry, and nasal examination. At the doses tested, no significant dissociative effects were evident using the Side Effects Rating Scale for Dissociative Anaesthetics.
The safety profile following treatment with ketamine was comparable to that seen with placebo.
Although patients did report side effects of fatigue, dizziness and feelings of unreality more often following treatment with ketamine than following treatment with placebo, no patient reported hallucinations and the side effects were generally reported to be of mild or moderate severity, and transient. No serious adverse events were reported and the incidences of associated adverse events were comparable for ketamine and placebo. Although study medication was administered intranasally, nasal signs and symptoms were few and inconsequential. A distinctive taste, however, was reported more often following treatment with ketamine than following treatment with placebo.In conclusion this randomized, placebo-controlled, double-blind study, in 20 patients, has demonstrated that intranasal ketamine is safe and effective for BTP [breakthrough pain]. Our findings augment an early but promising literature documenting the effectiveness of nasal administration of a variety of opioids for pain management in adults (Dale et al., 2002) .
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~http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875542/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875542/  Ketamine and chronic pain – Going the distance, David Barsook, 2009

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This important paper covers essential points not mentioned by many, thus quoted at length below:

“Ketamine, brain function and therapeutic effect – neuroprotective or neurotoxic

With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations ; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death. Here lies the conundrum the use of an agent that potentially deleteriously affect neurons that may already be compromised but may also have neuroprotective properties by mechanisms that include reducing phosphorylation of glutamate receptors resulting in decreased glutamatergic synaptic transmission and reduced potential excitotoxicity . Alternatively, ketamine may affect glia regulation of glutamate and inhibit glutamate release within glia. However, by whatever mechanism ketamine acts on CRPS pain, there does seem to be a dose/duration effect in that longer doses at levels tolerated by patients seem to prove more effective in terms of the duration of effects.

So what could be happening in the brain and what is required to alter brain systems and reverse the symptomatic state? Ketamine may diminish glutamate transmission and “resets” brain circuits, but it seems that a minimal dose and/or duration of treatment is required. Alternatively, ketamine may produce neurotoxicity and damage or produce a chemical lesion of affected neurons. These two issues are important to be understood in future trials. Reports from patients who have had anesthetic doses have included prolonged pain relief for many months. While the authors did not address issues such as the effect of dosing duration or repetitive dosing at say 6weeks, they did show a level of efficacy based on NNT that equals or betters most drug trials for this condition.”

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“Conclusions

As a community we have a major opportunity to define the efficacy and use of a drug that may offer more to CRPS (and perhaps other) patients than is currently available. This is clearly an opportunity that needs urgent attention and a number of questions remain to be answered. For example, is ketamine more effective in early stage disease? How does ketamine provide long-term effects? Further controlled trials evaluating dose, duration, anesthetic vs. non-anesthetic dosing are needed. Few of us really understand what it is like to suffer from a chronic pain condition such as CRPS. Ketamine therapy may be a way forward that can be brought into our clinical practice through further controlled studies that will allow for appropriate standards for use in patients.”

 

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The material on this site is for informational purposes only, and is not a substitute for medical advice,
diagnosis or treatment provided by a qualified health care provider.
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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!
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Carry On —> Inspiration


keep-calm-and-carry-on

This is a Cinderella story that will melt the most cynical heart.

Susan Boyle, the British singer, is an instant sensation!

Over 85.2 million viewers have seen her on YouTube in just one week – a record –

to watch her sing “I Dreamed A Dream from Les Miserables.

Born with brain damage, she was taunted all her life because she is slow.

Asked how she had the confidence to sing in front of a large audience, she says:

” I just had the ability to keep going.  You have to keep going.”

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…..a beautiful, inspiring video

of Nick Vujicic, born with no limbs, speaks to students

whose tears run down their cheeks, whose love pours out to him.

Nick has found the purpose of his life and has become strong

through the agony of learning how to overcome what had defeated him from birth.

The miracle we are looking for is inside each of us.·



For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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