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mr peabody

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For people suffering from chronic pain, Ketamine may be the answer

by Torsten | 28 Aug 2005

At his worst, Brett Lovell, 32, experienced such searing pain that he couldn't straighten his arm, and the fingers of his left hand curled up like a claw. The pain had him downing 25 pills a day. Then he undertook an experimental treatment - a 7-day coma in which he given an anesthetic called ketamine. The procedure gave him fleeting hallucinations, but it helped. "I can enjoy life better today," said Lovell, who is down to just one pill a day and can maneuver a computer mouse.

Ketamine is now being touted as a revolutionary treatment for a severe pain disorder. In the treatment, ketamine is infused intravenously and continuously while patients are supported by a ventilator - and are virtually dead - for days.

Robert Schwartzman, chairman of neurology at Drexel University College of Medicine, is has pioneered of the experimental treatment, which resets the link between the pain sensory neurons and the brain.

He equates the brain to a computer. "For five days we turn your computer off so you're not having any pain, he said. "When the brain is turned back on, the pain system is rebooted."

Considered a safe anesthetic, ketamine is chemically similar to PCP and causes inebriation, hallucinations and dissociation, the sensation that patients are not in their bodies.
These side effects have led to its popularity at raves and reports of use as a date-rape drug.

The extreme nature of treatment speaks to the desperation of those with chronic regional pain syndrome or reflex sympathetic dystrophy, a condition that affects 1.5 million Americans, according to the Reflex Sympathetic Dystrophy Syndrome Association. The syndrome produces intense, burning pain, and causes normally non-painful sensations, touch, movement and temperature - to be agonizing.

"It makes you feel like you've been doused in gasoline and set on fire," said Cynthia Toussaint, 44, a sufferer in Valley Village, Calif., who runs a nonprofit organization to help women in pain.

The condition can result from any type of injury, such as a turned ankle or carpal tunnel syndrome. It develops in 1-2 percent of fractures and 2-5 percent of peripheral nerve injuries. "The body's pain system, which is necessary to telling us something is wrong, goes awry in these cases. When pain fibers from the injury site activate, they trigger a chain reaction that changes the structure of the pain neurons. These changes provoke the neurons to fire even more - like a car engine revving out of control - which creates more pain," said Daniel Carr, chief executive officer of IDDS, a New York City-based company that is testing a ketamine nasal spray.

The syndrome often goes misdiagnosed and mistreated, said Schwartzman. Most of his patients have already seen 10 other doctors by the time they find him. And, many, especially children, face skepticism from their doctors, who think the patients are just trying to get attention.

"I got such horrible looks from doctors, like I had two heads," said Megan Vanatta, 21, of Washingtonville, N.Y., who has had the disorder since she was 7. "Doctors would ask, Are your parents fighting? Do your parents abuse you?"

The earlier the condition is treated, the more effective it seems to be - but there is no cure and no one treatment works universally, experts say. The ketamine coma is only for the most serious cases. A number of U.S. doctors use ketamine in small doses to treat pain while patients are awake, but Schwartzman and two German colleagues, Ralph-Thomas Kiefer and Peter Rohr, are the first to infuse it in comatose patients for up to seven days. So far, the trio has treated 26 American patients in Germany. All patients received significant temporary pain relief, and nine remain completely pain-free from nine months to three years after the infusion.

Ketamine is FDA-approved in the United States for two-day use when the patient is awake, but Schwartzman holds out little hope that the coma procedure will ever be allowed here. At Hahnemann University Hospital in Philadelphia, Schwartzman studies ketamine use for less severe patients and as boosters for those who have returned from Germany.

He just finished a study of 50 patients who were awake during five days of ketamine use, also not enough, he said, and plans to go back to the FDA in a couple of months for approval to try 10-day outpatient infusions. It may seem strange for a mind-altering substance to be used medically, but the history of ketamine is like many other drugs, if it works for one thing, scientists say, let's see if it works for another.

"The problem unfortunately is that we have so many horrible diseases related to the brain and so few drugs," said Bita Moghaddam, neuroscience professor at the University of Pittsburgh who uses ketamine in rats to mimic schizophrenic symptoms. If you have a drug you think is relatively safe, you have to use what you have.

Ketamine has also been used to study alcoholism and dementia, and explored as a treatment for sleep apnea and addictions and an aid in psychotherapy. While many severe pain sufferers are enthusiastic about the ketamine coma, researchers are more cautious.

"Initial observations are exciting," said Srinivasa Raja, director of pain medicine at Johns Hopkins University School of Medicine. "But it has to be tempered with the fact that they are not blinded observations. They have to be followed through over time."

Timothy Lubenow, a pain specialist at Rush University Medical Center in Chicago, had a patient who went to Germany and had great pain relief up until the plane ride back, he said. "She bumped her knee, which was the affected part, and the pain came back."

Schwartzman hopes that continuing research on treatments for severe pain will yield alternatives to the ketamine coma and that in the future "we won't need the ketamine sleep."

But, "right now, for dreadful patients, the only thing I've seen work is to have them go to sleep," he said.

http://www.shaman-australis.com/foru...ketamine-coma/

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I suffer from chronic neck/back pain and neuropathy. I was on opiates, Neurontin and Lyrica for years. The opiates worked for a time, but tolerance developed, and it will damage your GI. Lyrica and neurontin did nothing for my neuropathy. Then I tried cannabis, and Indica is the only strain that worked. I made a tincture with cannabis and pure grain alcohol. It works great. I take it sublingually. It works so much better than smoking it. I think the natural anti-inflammatories in the cannabis build up over time and help even more.

https://www.dmt-nexus.me/forum/defau...posts&m=668946
 
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mr peabody

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Low Dose Naltrexone (LDN)

by Joe Graedon | November 23, 2017

Here are two powerful opioid antagonists:

1) Naloxone (Narcan) given as an injection or nasal spray in the case of narcotic overdose, and

2) Naltrexone administered orally in the treatment of alcohol dependence, and to block opioid activity in the brain

There is a growing interest in low dose naltrexone, at doses ranging from 3-4.5 mg instead of the standard 50mg dose. At this low dose, there are reports that the drug can help treat a range of health problems with minimal side effects. These are off-label uses not approved by the FDA. They include chronic pain as well as the pain and inflammation of fibromyalgia, Crohns disease and multiple sclerosis. Here is one report.

Chronic Pain

I have dealt with body pain for many years. My pain increased gradually over the years and I just dealt with it. I wasnt using meds because I seem to have so many side effects from them. This summer my doctor put me on LDN, which has definitely helped me with my pain. I have not noticed any side effects.

Medical oversight is essential for people switching from opioids to LDN. Not all doctors know about Low Dose Naltrexone, so it is essential to find a doctor who is experienced in prescribing this medicine.

Far from being an opioid, Naltrexone blocks opioid receptors. You may have heard of a similar drug, Naloxone (Narcan), which is used to save persons who have overdosed on a narcotic.

How LDN works

There are several proposed mechanisms of action for this drug. The leading hypothesis is that LDN blocks opioid receptors. The body then compensates by manufacturing its own natural (endogenous) opioids. LDN may also have anti-inflammatory activity. Both Naloxone and Naltrexone appear to protect nerve cells and may have direct pain-relieving activity of their own.

LDN downsides

The FDA has approved a 50 mg pill of Naltrexone. To our knowledge, there are no Low Dose Naltrexone (LDN) pills available in drug stores. As a result, they must be specially prepared by a compounding pharmacy.

Although LDN is being prescribed by many physicians, long-term safety studies for chronic pain patients have not been carried out. Vivid dreams are common. Some people may find this an acceptable trade off rather than a disturbing complication.

Given the drug is off patent, we doubt that any pharmaceutical company will spend the money to prove safety and efficacy for chronic pain. That means the FDA is not likely to approve it for anything other than alcohol abuse or to block narcotic drugs, which is a shame because in doses of 3 to 4.5 mg it seems safer than many current pain meds.

LDN upsides

The drug should be relatively inexpensive compared to most other treatments for chronic pain. Normal dose naltrexone (50 mg tablets) cost under $40 for a months supply. A compounding pharmacy should not charge an outrageous amount for making LDN.

Naltrexone was first synthesized in the early 1960s. The FDA approved it in 1984 at doses of 50-100 mg to help treat opioid addiction.

https://www.peoplespharmacy.com/2017/11/16/low-dose-naltrexone-ldn-provides-surprising-pain-relief/
 
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mr peabody

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Cannabis is helping chronic pain patients reduce opioid use

by Mike Riggs | REASON | 28 Nov 2017

Chronic pain patients who enroll in New Mexico's Medical Cannabis Program are likely to reduce their dosage of opioids or even cease using opioids altogether, according to a new study from researchers at the University of New Mexico.

Participants in the program reported improvements in pain reduction, quality of life, social life, activity levels, and concentration, and few side effects from using cannabis one year after enrollment in the MCP.

The UNM researchers concluded clinically and statistically significant evidence of an association between MCP enrollment and opioid prescription cessation and reductions and improved quality of life warrants further investigations. That finding dovetails with a growing body of research that medical marijuana works as well as some prescription drugs for the treatment of pain, while imposing fewer side effects on users.

Researchers at the University of Michigan, for instance, reported in 2016 that chronic pain patients participating in Michigan's medical marijuana program reported a large reduction in opioid use and improved quality of life. Other studies have found that doctors in medical marijuana states prescribe fewer prescription drugs, and that states with legal medical marijuana have experienced a smaller increase in opioid overdose rates compared to states where medical marijuana is not legal.

The more of these studies I see, the more I'm reminded of something psychiatrist Scott Alexander noted about the renaissance in psychedelic research:

There's a morality tale to be told here, about how the War on Drugs choked off vital research on some of the most powerful psychiatric compounds and cost us fifty years in exploring these effects and treating patients. Marijuana's Schedule I status has long precluded it from competing with prescription opioids as a treatment for chronic pain.

http://reason.com/blog/2017/11/28/new-mexico-study-suggests-medical-cannab
 
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mr peabody

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Kambo and chronic pain

Psychedelic Times | 21 Dec 2016

Kambo is the poison of the giant leaf frog 'Phyllomedusa bicolor', which it excretes through its skin. The secretion is said to generate an altered state of reality, clear inner sight and a resurgence of long forgotten memories.

Kambo is known as the vaccine of the forest; in Portuguese, due to its use as a treatment for a spectrum of diseases including migraines, depression, blood circulation, organ diseases, fertility problems, and cancer. Most notably, though, it is used to treat pain. Research conducted since 1979 has shown that kambos powerful peptide content makes it a natural and holistic painkiller. Of the nine peptides in kambo, some of the most notable include phyllomedusin, which contributes to deep purging and detoxification; caerulein and sauvagine, which heighten sensory perception and stamina and have powerful pain-relieving properties; and dermorphin and deltorphin, which provide an opioid-like effect, 400 times more powerful than morphine.

In addition to its analgesic qualities, Kambo is a powerful anti-inflammatory and anti-microbial. While research has yet to confirm its potential, traditional kambo treatment administered over a series of sessions could prove to be a powerful tool in the fight against many diseases.

While decreasing pain is obviously an important effect of Kambo, it also works to attack the modern plague of addiction. Simply put, the less pain you have, the less likely you will feel the need to seek out opioids or other pain medications that are addictive. For those suffering from addiction, Kambo can provide an alternative method of pain management while they work to kick the addiction. Essentially, Kambo has a one-two punch effect; it treats pain and, in doing so, helps individuals decrease dependence on more addictive pain management medications.

https://psychedelictimes.com/kambo/h...eat-addiction/
 
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mr peabody

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Ketamine treatment for chronic pain on the rise

by Pauline Anderson | Medscape | 4 Apr 2017

Pain medicine specialists are concerned about the growing use of the anesthetic ketamine in private pain clinics across the United States.

There are reports of some centers providing "cash only" intravenous (IV) ketamine infusions to patients coming in with a variety of pain disorders, they say.

"It's like a Wild West out there," said Steven P. Cohen, MD, professor of anesthesiology and critical care medicine and of physical medicine and rehabilitation at Johns Hopkins Hospital, Baltimore, and at the Uniformed Services University of the Health Sciences, Bethesda, Maryland.

"It can be very lucrative" for doctors running these clinics, said Dr Cohen.

At least some of those doctors are pain medicine specialists. Dr Cohen and other experts addressed a symposium during the American Academy of Pain Medicine (AAPM) 2017 Annual Meeting titled, "Ketamine for Chronic Pain: Panacea or Snake Oil?"

Ketamine, an N-methyl-D-aspartic acid (NMDA) receptor antagonist, was first used as an anesthetic in 1966. In recent years, interest in the drug as a possible effective therapy for myriad chronic pain conditions has resurged, including neuropathic pain, complex regional pain syndrome (CRPS), fibromyalgia, postherpetic neuralgia, migraines, and spinal cord injury.

"Pain is the biggest cause of disability in the world, and there is no really good treatment for it," Dr Cohen said in an interview with Medscape Medical News.

Ketamine's significant psychomimetic and euphoric properties have led to abuse. Oral ketamine has become a popular nightclub drug. "It's one of the biggest causes of car accidents in many parts of Asia; people drive while high on ketamine," said Dr Cohen.

As well as pain, ketamine is used to treat depression and post-traumatic stress disorder. The relationship between chronic pain and depression "is very complicated" and something of "a two-way street," said Dr Cohen.

"Chronic pain can cause people to become depressed, but depressed persons who hurt their back or who have surgery are more likely to develop chronic pain. "These patients suffer physically and emotionally, and ketamine sometimes gives them euphoric feelings and they feel better," added Dr Cohen.

"But although ketamine is "a very, very potent analgesic, it has drawbacks, one of them being that its effects last for only a short period," said Dr Cohen. "As well, we don't know the long-term effects and unfortunately it's associated with significant side effects," he added. "Adverse effects can include nausea, headaches, fatigue, and dysphoria."

In demand

In providing ketamine, pain clinics are answering to a growing public demand. "Patients coming to a doctor know what they have and because of the Internet, they know what they want, and they request it," said Dr Cohen. "People may come in with complex regional pain syndrome and say they want a ketamine infusion because nothing else works."

"In addition to private clinics, some academic centers provide ketamine infusions. But as a teaching hospital, we are required to accept whatever Medicare and Medicaid pays, and in some cases, this can be a money loser,"
said Dr Cohen.

"That's not the case with private clinics," he noted. "They can charge whatever they want."

"As a result, prices for ketamine infusions vary widely, and in his region they can range from $500 to sometimes more than $2000, depending on the duration,"
Dr Cohen noted.

Clinicians are worried about the unregulated use of ketamine at these private clinics.

Concern about off-label use of ketamine for depression without a firm evidence base has already been raised among psychiatrists. To answer some of these concerns, in March 2017, a group of psychiatrists issued a consensus statement for ketamine use for severe depression and other mood disorders.

The panel recommended that before considering ketamine, clinicians should confirm that the patient meets the appropriate diagnostic criteria for depression, has undergone an adequate trial of approved antidepressant therapies, and has no history of substance abuse or psychotic disorders.

Now, pain doctors too want some direction. Oscar Deleon-Casasola, MD, president of the American Society of Regional Anesthesia and Pain Medicine, confirmed to Medscape Medical News that his association is preparing guidelines for use of ketamine for pain management.

"It's too early to say what areas the guidelines will cover, but we will look at the evidence as it pertains to pain medicine indications," said Dr Deleon-Casasola.

He added that the society "would like to have the guidelines out within the next 6 months."

Ajay Wasan, MD, professor of anesthesia and psychiatry, University of Pittsburgh, Pennsylvania, who also addressed the AAPM ketamine session, pointed out that a lot is still unknown about the use of ketamine for chronic pain.

"So guidelines are not going to be a recipe for what clinicians should and should not do," Dr Wasan told Medscape Medical News. "The data just isn't strong enough to say that."

While pain experts work out guidelines surrounding ketamine use, they're gathering information on whether this drug actually works in chronic pain. At the ketamine session, delegates learned that ketamine elicits analgesia primarily through noncompetitive antagonism of the NMDA receptor at the level of the spinal cord and higher brain centers, which play a major role in nociceptive transmission, cognition, mood regulation, opioid tolerance, and central sensitization.

But the drug also acts through various other receptors, including α-amino-3-hydoxyl-5-methyl-4-isoxazole propionate, kainite, and γ-amino-butyric acid.

In the literature on ketamine for CRPS, Dr Cohen cited a randomized, double-blind, placebo-controlled trial that compared a 4-hour ketamine infusion to saline on 10 consecutive workdays in 19 patients with CRPS. The maximum ketamine infusion rate was 0.35 mg/kg per hour, not to exceed 25 mg/h over a 4-hour period. All patients were given midazolam and clonidine.

That study showed pain scores decreased from a mean of 7.7 to 6.1 at 2 weeks in the treatment group, with the effect maintained throughout the 12-week study period, while the placebo group had a nonsignificant change in pain scores.

In this study, the ketamine group had a decrease in nocturnal awakenings at 12 weeks but no increase in quality of life compared with placebo. About 44% of the ketamine and 20% of the placebo patients experienced adverse events, including dysphoria and fatigue. No patient reported psychomimetic effects.

Blinding issues

But this and other studies, including those involving patients with neuropathic pain after a spinal cord injury, were hampered by their small numbers, limited generalization, and lack of effective blinding, which often skews pain relief outcomes, said Dr Cohen. Research shows that lack of adequate blinding in randomized controlled trials can exaggerate the effect size by 33%, he added.

Most research on ketamine for chronic pain has focused on IV infusions, which limits its use as long-term therapy and dramatically increases the cost, Dr Cohen said. Oral and intranasal ketamine have been shown to be effective in clinical practice and in research studies, he said.

Dr Cohen concluded that ketamine is no miracle drug, but it's also likely not just a passing fad. "It falls somewhere in between," he said.

Dr Wasan agreed that the data "are not conclusive" and that the use of ketamine in patients with chronic pain "needs to be evaluated more carefully."

During the session, he cited a recent review (Anesthes Analges. 2017;124:661-674), which he called one of the best to date. Here, researchers reviewed 26 articles on IV ketamine infusions, most involving CRPS or mixed neuropathic pain.

The review concluded that the current state of the literature leaves the use of ketamine infusions without meaningful guidance from high-quality comparative evidence.

Many unknowns

While a variety of conditions, including CRPS, might benefit from ketamine infusions, "It's not clear at this point exactly how to administer it," Dr Wasan said. "We don't really know how exactly how much ketamine to infuse or for how long, or how frequently to give the infusions."

It's also possible that responders in the pain trials had major depressive disorder (MDD). Some 50% to 75% of patients in pain clinics have MDD.

"It could be that the people who respond best are those with both pain and depression," Dr Wasan said. "In future trials of IV ketamine, researchers may want to include patients with chronic pain and MDD and track the improvement in both over a period of at least a month."

A third speaker at the AAPM session, Aubrey Verdun, MD, Anesthesiology and Pain Management, Walter Reed National Military Medical Center, Bethesda, Maryland, presented research on low-dose ketamine for postoperative analgesia.

"The evidence here," said Dr Verdun, "shows that ketamine reduces pain scores, decreases opioid consumption by up to 40%, has an excellent safety profile, and facilitates recovery and rehabilitation in the postoperative period."

"Uncontrolled acute pain,"
said Dr Verdun, "can lead to chronic pain, which affects over 70 million people and is on the rise. The cost of chronic pain to the US economy is now over $100 million per year. Ketamine is not approved for chronic pain management and may never be," said Dr Cohen.

"You have an incredibly cheap drug, and there's no patent protection, so no company is going to do the 350-patient, double-blind study that costs $100 million."

https://www.medscape.com/viewarticle/878159#vp_3
 
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Psychedelic plant Salvia targets pain receptor

by Leslie Lang-UNC | 22 Mar 2012

The discovery of how the psychedelic Salvia affects the brain could lead to new avenues for treating chronic pain.

At the molecular level, drugs like salvinorin A (the active ingredient of the psychedelic plant Salvia divinorum) work by activating specific proteins, known as receptors, in the brain and body.

Salvinorin A, a potent naturally occurring psychedelic, is unusual in that it interacts with only one receptor in the human brain—the kappa opioid receptor (KOR). Scientists know of 4 distinct types of opioid receptors, but until now the structure of the ‘salvia receptor’, and the details about how salvinorin A and other drugs interact with it, was a mystery.

In a research paper published in the journal Nature, scientists from the University of North Carolina at Chapel Hill, Scripps Research Foundation, and 2 other institutions revealed the first-ever glimpse of the complete structure of the KOR.

“Once we see the structure of the KOR receptor, it becomes easier for us to develop drugs that target the receptor in ways that might be beneficial for medical therapy,” says Bryan Roth, professor of pharmacology and one of the paper’s authors. “Drugs that block the receptor are potentially useful for treating a number of serious illnesses including chronic pain, cocaine addiction, and other diseases.”

The KOR is responsible for the action of drugs that affect human consciousness, awareness of pain, and mood. KOR is the only receptor that binds salvinorin A—the active ingredient of the psychedelic plant Salvia divinorum. Salvia use has surged among teenagers and young adults with more than 5 percent reporting usage in the past year, according to the National Institute on Drug Abuse. Knowing KOR’s structure offers insights about how salvia and other drugs work. The finding also could help scientists design medicines that either activate or block KOR to benefit patients.

The research team crystallized KOR using JDTic, a drug currently in early-stage human trials; JDTic keeps KOR in an inactive state and blocks the actions of salvinorin A. In studies using animal models, JDTic has shown promise for treating addiction, depression, and anxiety.

The downside of JDTic and similar drugs targeting KOR is that they can exert their actions for weeks whereas most prescribed medicines are cleared within 18-24 hours. “Now that we have the [KOR] structure, it opens up the possibility for us to make drugs that have the same action as JDTic but have better pharmaceutical properties,” says Roth.

The research also resolves longstanding scientific debates about how drugs bind to KOR. The study found that compared to other receptors the binding site on KOR is enormous, allowing drugs to bind to it in more than one way.

"In addition," Roth says, "the research could help scientists develop drugs that activate KOR in the body without affecting the brain, which could be useful for treating chronic pain, kidney problems, and many other disorders."

https://www.futurity.org/hallucinoge...pain-receptor/
 
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The science of salvia

By Thomas Varley | Psymposia | 7 May 2018

So what do we know about salvia divinorum’s pain-relieving properties? The active compound in any preparation of the plant is a molecule called salvinoin-A, which is almost unique among psychedelic drugs in that, while almost all other psychedelics work by activating some combination of serotonin and dopamine receptors, salvinorin-A has an affinity for the somewhat-obscure opioid receptor: the kappa-opioid receptor (usually abbreviated as the KOR), which, as far as we know, is not targeted by any other commonly-used drug. Unlike a plant like cannabis, which has thousands of individual molecules that synergize to create its effect, Salvia divinorum’s effects come exclusively from salvinorin-A. While metabolites similar to Salvinorin-A have been isolated from the plant, none of them appear to have appreciable psychoactive effects (although synthetic derivatives have been created that show comparable effects).

In a very simplified sense, the kappa-opioid receptor can be thought of as the opposite twin of the more well-known mu-opioid receptor, which is what drugs like morphine target. Together, they seem to perform a balancing act that is integral to our own innate ability to learn. The mu-opioid receptor mediates ‘rewards.’ Behaviors that trigger its activation result in feelings of well-being and euphoria, which can become addictive. The brain learns to do whatever it is that triggers the mu-opioid receptor. The kappa-opioid receptor, on the other hand, seems to do the opposite. Stimuli that triggers that receptor and the feelings created are of stress, dysphoria and aversion. There are other interesting symmetries: mu-opioid receptor agonists cause itching while kappa-opioid receptor agonists suppress it. Taking something like salvia with something like heroin also seems to blunt the effects of both drugs, which is what you would expect to see if the mu and kappa opioid receptors worked in opposition. Together they help us navigate complex environments full of both rewarding and aversive behaviors, and when everything is working smoothly, they balance one another out. They both, however, seem to dull pain.

The pain-killing effects first discovered by the Mazatec people have borne out under scientific scrutiny. In a series of somewhat heart-breaking studies, scientists took rats and mice and subjected them to a battery of ways to induce pain, which range from putting them on hot-plates that burn their feet, to shooting their tails with lasers, both with and without infusions of Salvinorin-A. Across the board, the mice that were treated with Salvinorin-A showed fewer signs of experiencing pain. The effect is clear: Salvinorin-A is an effective analgesic. In fact, it’s very effective: it’s active at extremely low doses (200ug, making it one of the strongest known, naturally occurring psychoactive compounds) and doesn’t seem to have any point of lethal overdose, unlike opiate painkillers, where high potency usually translates into increased risk of death. Even chronic exposure to high doses doesn’t do damage to vital organs.

The non-addictive nature observed by anthropologists and user-surveys has also been validated by animal studies. The usual tests for addictiveness indicate that Salvinorin-A is extremely unlikely to be addictive. It may even have anti-addictive properties: beyond simply not having effects seen as indicative of addictive potential, Salvinorin-A has been found to exhibit the opposite effect. For example, almost all addictive drugs increase the amount of dopamine activity in a brain region called the nucleus accumbens. Salvinorin-A not only fails to increase dopamine in this region, it seems to actively suppress it. Similarly, in tests of addictive drugs, many animals will show ‘conditioned place preference,’ frequently returning to areas where they received infusions of the drug, even when they’re not receiving any. Salvinorin-A has the opposite effect, creating ‘conditioned place aversion.’ As with the pain-relieving properties, the evidence is clear: Salvinorin-A (and by extension Salvia divinorum) is unlikely to have the same addictive qualities that can make opiate painkillers dangerous. Drugs like Salvinorin-A have even shown promise as a treatment for addiction to other substances, including cocaine and alcohol.

Thus far, we have a powerful, non-addictive painkiller that is physiologically safe, with no known lethal overdose effect. So what’s the problem? Why aren’t we getting Salvinorin-A infusions in hospitals?

Why it’s not a great medicine

While Salvinorin-A does have some extremely appealing properties, there are a few things that make it completely unsuitable for use as a replacement for our current pain medications. One is that it is only active for a brief period. Anyone who’s smoked Salvia knows that a user will only be under the influence for a few minutes, and even when administered as a quid, the effect doesn’t last longer than an hour. While short-acting pain-killers can be useful in surgery (fentanyl being one famous example), for extended pain management, they leave much to be desired. The other negative, which is something of an elephant in the room, are the hallucinations.

The effects of Salvinorin-A when rapidly administered (such as smoking or injection), or administered in high doses have the potential to be extremely unpleasant. The ‘trip reports’ section of Erowid’s Salvia divinorum vault is full of experiences that range from mildly-distressing, to traumatically disturbing (one that sticks out in my memory is one of a young man who smoked it and felt himself become part of some kind of cosmic machine made of meat). While experienced psychonauts may be able to manage these experiences with appropriate preparation and knowledge, a hospital is possibly one of the worst places to experience a profound and florid psychosis. Earlier I mentioned being given an i.v. of Dilaudid while in the hospital for kidney stones, and I cannot imagine how awful it would have been to have my painkiller also serve as a ticket to Cthulhu’s birthday bash. Such experiences are hard enough in a normal frame of mind, and as far as sets and settings go, being scared, vulnerable, and in pain seem like the worst possible place to embark on a psychic journey.

Looking forward: What we can learn from salvia

While Salvinorin-A may not make its way into a medical setting, this research can be used to start looking for drugs similar enough to Salvinorin-A to take advantage of the positive effects. We now know that selective kappa-opioid receptor agonists are physically safe, effective pain-killers with low addictive potential.

There has been some evidence of analogues of Salvinorin-A that cannot cross the blood-brain-barrier (and therefore cause strange effects to consciousness). Clinical trials of a peripherally selective kappa-opioid receptor agonist called asimadoline have been very promising, especially for irritable bowel syndrome (one of the conditions the Mazatec have been using Salvia divinorum to treat for centuries). Other drugs have been developed that try to combine traditional opiate drugs with kappa-opioid receptor agonists in an attempt to balance the effects and reduce the risk of addiction. While psilocybin, LSD, and ibogaine have recently received significant press for their potentially anti-addictive properties, Salvia divinorum shouldn’t be forgotten and may yet have a role to play in the development of our understanding and treatment of addiction.

For individuals with painful conditions like migraines, or IBS, it is certainly possible that they could take inspiration from the Mazatec people and grow their own medicine. The Indigenous people of the Americas were using it as an effective medicine while European doctors were still debating whether it was a good idea to wash their hands before surgeries, and while simply chewing the raw leaf will have some consciousness-altering effects, some may feel that it’s a worthwhile trade-off.

Sometimes there can be a feeling that psychedelic research must necessarily lead to the legalization or prescription of the drug in question. The research into cannabis, psilocybin, MDMA, ibogaine, and LSD are all currently aimed at bringing these compounds into a Western medical framework so that they might one day be prescribed by doctors in white lab coats. There is another side of psychedelic research that is decidedly less glamorous but just as important: doing basic research on Salvia divinorum and Salvinorin-A may never result in someone filling a prescription for salvia at the local CVS, but the things we learn may help change the face of medicine.

https://www.psymposia.com/magazine/s...not-addictive/
 
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Salvinorin A: killing pain without addiction?

The Psychedelic Scientist | 16 Jun 2016

Salvia divinorum is a unique psychoactive plant that has been used in religious ceremonies for centuries. But could its use go beyond the spiritual? Salvia has also been used traditionally as a painkiller at low doses, and recent research suggests that Salvinorin A, the main psychoactive compound in Salvia, may be the key to developing a non-addictive painkiller. Could this mystical plant really have medical potential?

A common issue with modern painkillers is that they are often very addictive. Many effective painkillers, such as morphine or codeine, can lead to addiction with improper use. In America, more people die from prescription drug abuse than heroin. An ideal painkiller would relieve pain without causing addiction; this is where Salvia may come in useful.

Typical painkillers, like morphine, activate the mu-opioid receptor (MOR). Activation of this receptor is thought to be a factor in addiction, causing euphoria as well as relieving pain. Salvinorin A, Salvia’s active ingredient, activates the kappa-opioid receptor (KOR). Drugs that activate the KOR can sometimes have painkilling properties; ketamine is one example. Most importantly, KOR activators don’t have the addictive properties that MOR activators do.

But it’s not as simple as switching from MOR activators to KOR activators. KOR activators have their own problems when used as painkillers. They often cause unpleasant feelings, including nausea and confusion. Not to mention, KOR activators (especially Salvinorin A) can have intense psychedelic effects.

One group tested the natural painkilling properties of Salvinorin A in mice. They found that injecting mice with as little as 10 micrograms of Salvinorin A reduced their response to uncomfortable stimuli, such as a steadily warming hot-plate (McCurdy et al 2006). Although the effect was short-lived, and only a few forms of pain were measured, this study seems to indicate that Salvinorin A could be a natural painkiller.

Although this is promising, Salvia by itself won’t be an effective painkiller. Its effects don’t last long enough and patients won’t necessarily want to go on a psychedelic journey each time they want to treat their pain.

However, scientists have begun using the Salvinorin A molecule as a scaffold for developing unique new painkilling drugs. Salaga et al. (2015) have developed a Salvinorin A analogue, imaginatively named ‘5a’, that has anti-itching properties in mice. White et al. (2015) are developing a Salvinorin A analogue with, RB-64, which has painkilling effects in mice that last much longer than Salvinorin A alone. In both cases, these drugs don’t cause the typical unwanted effects of Salvinorin A such as anxiety or confusion.

https://thepsychedelicscientist.com/...tion/#more-229
 
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CBD and THC

by Nishi Whiteley

While there are over 100 different cannabinoids that can occur in cannabis, the two most well known and studied compounds in the cannabis plant happen to also be the two that occur in the largest volume: THC, and cannabidiol, known as CBD. Like all other cannabinoids, these two must be heated to convert the cannabinoid acid to the active cannabinoid. THC is the primary psychoactive component of cannabis. CBD is considered to be non-psychoactive, and when used in conjunction with THC, helps dampen the psychoactivity and other side effects some people consider undesirable. Both cannabinoids have an impressive list of ways they support the human body.

THC is a strong anti-inflammatory and pain killer and has been shown to reduce the amyloid plaques in the brain that cause Alzhiemer’s. In pre-clinical trials THC has been proven to reduce levels of vascular endothelial growth factor (VEGF) in glioma (brain cancer) cells. This is important because a reduction in VEGF means that brain cancer tumors are unable to grow the new blood vessels they need to sustain themselves, grow and spread. This discovery offers great promise for the treatment of brain cancer.

CBD is the second most common cannabinoid in cannabis, and can generally represent 0.1-12 percent of the cannabinoid content of the the plant. CB-rich cannabis (4% or more) provides potent therapeutic benefits without the euphoria or lethargy of many high THC varieties. CBD and THC are believed to have a synergistic effect meaning that when they are both present at therapeutic levels, they are more effective together than they are alone. While THC is known for its psychoactive properties, CBD may be best known for its ability to counterbalance anxiety, tachycardia (rapid heartbeat), hunger and sedation caused by THC and its ability to control severe forms of epilepsy.

CBD was once considered a minor cannabinoid under the shadow of THC. We know now is that CBD is as beneficial and versatile a cannabinoid as THC in addressing many hard to manage conditions such as diabetes, rheumatoid arthritis, cancer, epilepsy, antibiotic-resistant infections, alcoholism, PSTD and neurological disorders. CBD is a strong anxiolytic (reduces anxiousness), anti-convulsant, anti-emetic (reduces nausea), anti-inflammatory, antioxidant (stronger than vitamins C & E), anti-depressant and anti-psychotic properties. One of the most exciting aspects of CBD is its combined strong anti-inflammatory, anti-oxidant and neuro-protective properties which yields great promise for the treatment of Alzhiemer’s, Parkinson’s and all neurodegenerative-related diseases. CBD also helps regulate blood pressure and is cytotoxic to breast cancer and certain other types of cancer cells while protecting healthy cells.

In a recent study, the European Journal of Pain used an animal model to see whether CBD could help people with arthritis manage their pain. They noted a significant drop in inflammation and signs of pain without side effects. The same report studied CBD for general chronic pain. Researchers compiled the results of multiple systematic reviews covering dozens of trials and studies. Their research concluded that there is substantial evidence that CBD is an effective treatment for chronic pain in adults.

https://mychronicrelief.com/cannabis-101-thc-cbd/
 
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Nabilone for chronic pain

Nabilone is a synthetic cannabinoid with therapeutic use as an antiemetic and as an adjunct analgesic for neuropathic pain. It mimics tetrahydrocannabinol (THC), the primary psychoactive compound found naturally occurring in cannabis.

The FDA has indicated nabilone for chemo-induced nausea/vomiting. In countries such as Canada, it is widely used as an adjunct therapy for chronic pain management. Numerous trials and case studies have demonstrated effectiveness for relieving fibromyalgia and multiple sclerosis. The conditions that have seen published clinical trials of nabilone include parkinsonism, chronic pain, dystonia and spasticity neurological disorders, multiple sclerosis, and the nausea of cancer chemotherapy.

Nabilone was approved in Austria to treat chemo-induced nausea in 2013; it was already approved in Spain for the same indication, and also in Belgium to treat glaucoma, spasticity in Multiple Sclerosis, wasting from AIDS, and chronic pain.

https://en.wikipedia.org/wiki/Nabilone

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Managing chronic pain with low dose nabilone

Low dose nabilone was found to reduce clinical pain in Motor Vehicle Accident patients despite an increase in their general daily activities, work tolerance and socialization. The degree of pain and time to return to work following intervention has been evident. Improvement of sleep was consistent, with fewer awakenings and more refreshing mornings. Patients were less anxious and irritable, and their appetite increased.

https://www.jpain.org/article/S1526-5900(000129-6/pdf
 
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THC oil for chronic nerve pain


New imaging findings show how THC, the psychoactive component of cannabis, works in the brain to effectively treat chronic neuropathic pain. Results of a small randomized, double-blind, crossover trial show that THC-induced pain relief was associated with reduced functional connectivity between the anterior cingulate cortex (ACC) and the sensorimotor cortex. "The main message of this paper is that THC, the psychoactive component in cannabis, does seem to exert a beneficial effect on proven chronic nerve pain. "This effect seems to involve a breakdown in functional connectivity between brain regions that process different dimensions that construct the experience of pain," study author Haggai Sharon, MD, who leads the Consciousness & Psychopharmacology research team at Sagol Brain Institute, Tel Aviv, Israel, told Medscape Medical News.

Mechanism unknown

Although previous research has shown that treatment of chronic pain remains the number one medical use for cannabis, the underlying neurologic changes associated with clinical benefit remain unknown. Sharon said the researchers expected these mechanisms to be "complex and involve large-scale brain changes" because humans naturally feature cannabis receptors in many regions of the brain, including the ACC. A previous neuroimaging study showed THC was associated with decreased ACC activity in healthy participants. Those investigators note that peripheral changes alone could not sufficiently explain the dissociative properties of THC on pain, supporting the role of the brain — and the amygdala in particular — in modulating sensory improvements.

For the current study, researchers enrolled 17 individuals with chronic neuropathic lower-limb pain (mean age, 33 years). All were recruited at The Institute of Pain Medicine at the Tel-Aviv Sourasky Medical Center in Israel. The researchers restricted the study to men; women "were excluded due to evidence that menstruation-related hormonal fluctuations may alter pain sensitivity," they note. After exclusions, investigators assessed the effect of a single sublingual dose of THC or placebo on visual analog scale (VAS) scores and resting-state brain connectivity of the ACC in 15 participants using functional MRI (fMRI). Participants completed the State-Trait Anxiety Inventory–State questionnaire and underwent heart rate and blood pressure measurements at each session. They also underwent nontask resting state fMRI, followed by receiving either 0.2 mg/kg THC oil or placebo placed sublingually. The average THC dose was 15.4 mg.

Investigators obtained a second fMRI scan about 2 hours after THC or placebo administration. Following a washout period that averaged 3 weeks, participants crossed over to the other intervention group and repeated the protocol. The fMRI data were acquired by using a 3T MRI scanner, and functional scans were obtained by using T2-weighted echoplanar images. Sharon and colleagues also performed graph theory analysis, which allowed them to examine the interconnectivity of 11 brain regions. They looked at the ACC, amygdala, secondary somatosensory cortex, middle cingulate cortex, and dorsolateral prefrontal cortex (DLPFC), among others.

Pain scores, imaging findings align

The reduction in VAS pain ratings reported after THC administration was significant compared with preintervention scores (P < .05) and between THC and placebo (P < .005). In contrast, VAS scores did not differ significantly before and after administration of the placebo. In addition, the researchers reported a reduction in functional connectivity between the ACC and the sensorimotor cortex, which correlated with changes in subjective pain ratings after THC treatment. They also reported changes in three clusters within the sensorimotor cortex: the right and left secondary somatosensory cortex and the right motor cortex. No such relationships were observed between pain scores and functional connectivity among these brain structures following placebo administration.

Buoyed by results showing connectivity changes among these brain regions, the investigators then expanded the study to all regions considered part of the so-called chronic pain network. They reported significant changes in global efficiency of the middle cingulate cortex between THC and placebo interventions, for example, again using graph theory analysis. In addition to a reduction in the whole network, decreases in the DLPFC cluster aligned with the lower pain scores following THC administration. Again, these changes were not observed with the placebo. Anxiety scores, blood pressure, and heart rate measures did not change significantly after administration of THC vs placebo.

New insights for drug development

THC may provide relief by disrupting the synchrony and integration between the ACC and sensorimotor cortex pain-processing pathways. "The relation between analgesia and a mind-altering substance that induces clinical dissociation in many domains is fascinating," Sharon said. "Moreover, delineating these mechanisms may assist in better patient selection and control of side effects…and drive new insights into analgesic drug development. "The current findings reinforce "the seminal role of nonsensory aspects of pain as building the aversive experience that accompanies pain and offer a new insight into analgesia," Sharon said. "It isn't just about numbing the sensations. THC can also act by modulating the subjective suffering."

Interestingly, the research also showed that the higher the functional connectivity between the ACC and sensorimotor cortex at baseline — before administration of THC — the greater the benefit in terms of pain relief. "Our results suggest that this regional functional connectivity may also serve to predict the extent of pain relief induced with THC," the investigators write. "This was a major and unexpected surprise," Sharon added. "Characterizing predictors for response is, of course, of major importance, as the question of correct patient selection for pharmacotherapy in chronic pain is a crucial one."

Larger studies are now warranted to examine the reproducibility of the results, the investigators note. Future trials should also examine different cannabinoids, as well as include patients with conditions other than chronic radicular pain to determine whether the findings are specific to neuropathic pain only or apply to other chronic pain states. "We plan to further explore predictors for response at the individual patient level, better understand the relation between dissociative effects on cognitive emotional and sensory processing and clinical analgesia, and the relation of these processes to secondary autonomic and homeostatic regulatory mechanisms," Sharon said.

Commenting on the findings for Medscape Medical News, Mark Wallace, MD, professor of clinical anesthesiology at University of California San Diego, described the findings as interesting. "I would also be interested in seeing the effects of different doses," Wallace said. "We have already shown there is a therapeutic window of THC on pain relief, with high doses actually worsening pain and low doses relieving pain," he added.

https://webcache.googleusercontent.com/search?q=cache:joXhOhJfxGEJ:https://www.medscape.com/viewarticle...lnk&gl=us#vp_2
 
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Ketamine Infusion Therapy (KIT) for Fibromyalgia and Rhumatoid Arthritis


Treatment with intravenous ketamine eased pain significantly in a patient with rheumatoid arthritis (RA) and fibromyalgia, a case report shows.

The report, “Intravenous Ketamine Alleviates Pain in a Rheumatoid Arthritis Patient With Comorbid Fibromyalgia,” was published in the journal The Journal of Medical Cases.

Patients with RA are at increased risk to develop fibromyalgia. Both disorders disproportionally affect women. RA may be treated with diverse types of medications that target pro-inflammatory cytokines — molecules released by immune cells — including analgesics, non-steroidal anti-inflammatories (NSAIDs), glucocorticoids, and disease-modifying therapies.

However, lack of response in some patients and medication-related problems warrant evaluation of alternative treatments.

Intravenous (IV) ketamine has been an FDA-approved medication for nearly 50 years. Ketamine blocks the NMDA (N-methyl-D-aspartate) receptor, which is key in neuronal communication and is involved in regulating pain signals in the brain and spinal cord. Excessive activation of this receptor may cause toxicity, leading to various pain disorders.

By blocking NMDA receptors, ketamine may correct this over-activation. However, ketamine’s therapeutic effects go well beyond its levels in the body, which leads scientists to speculate that it induces secondary changes that result in durable benefits.

A combination of analgesic, immunomodulatory and anti-inflammatory effects have been proposed for ketamine, which makes it promising for treating RA, according to the authors.

This report describes the case of a 49-year old woman with RA whose arthritis did not respond to conventional treatment options and resulted in permanent, extreme pain. She reported joint pain with stiffness in the morning in hands and shoulders, which limited finger and wrist movement and reduced her quality of life significantly.

The patient also had diffuse muscular pain and met diagnostic criteria for fibromyalgia.

"Several treatment options, including physical therapy and conventional medications, did not achieve adequate pain control for either condition, so I decided to use [IV] ketamine as an alternative therapeutic option,” Ashraf Hanna, MD, the study’s lead author, said in a press release.

The patient started a 10-day IV ketamine infusion treatment for four hours per day. The initial dose was 428 mg, gradually increased to 1,063 mg.

She reported decreased pain after the first infusion session, and being almost pain-free after the last session. She also was no longer experiencing RA symptoms, including joint pain and morning stiffness.

Although he noted this is the first published report on the use of ketamine in RA, Hanna considered that “ketamine appears to possess unique immunomodulatory and analgesic properties that effectively reduce inflammation and reduce pain without the use of opioid/NSAID analgesics.”

The authors cautioned that the findings are from only one patient and did not compare ketamine with placebo. However, “we are hopeful that future adequately powered and placebo-controlled clinical trials may confirm that ketamine is safe and effective for the treatment of autoimmune diseases such as RA,” they wrote.

Unlike in the past, ketamine’s effectiveness is now recognized by diverse insurance companies. “We hope to continue to add new Ketamine-compliant insurance companies in 2018,” Hanna said.

“I have provided over 8,000 ketamine infusions and have seen so many incredible successes over the past 5 years. Some of my patients were unable to move a limb or walk, and now they have complete mobility and can walk unaided.” Hanna said.

https://fibromyalgianewstoday.com/20...ra-study-says/
 
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Recommended CBD regimen for pain management

by Jose Marques Lopes, PhD | 22 May 2018

When formulating a CBD regimen for a specific disease or illness (like chronic or neurological pain), it's important to understand that CBD should be used regularly for maximum relief, meaning it is used as a preventative first. It can also be used to manage acute flair ups, but preventative maintenance is the key. As with any other dietary supplement, you want to establish a baseline concentration in your system.

Daily Maintenance

In order to manage pain, it is recommended to ingest full spectrum CBD oil daily in the form of tinctures or gel capsules. The ingredients in the two products are the same; the only difference between the two is the form factor and dosage, pills vs. sublingual tinctures. Those suffering from any kind of pain start with 5-10mg per day of CBD. If relief is not felt at this dosage, it is suggested to increase that by 5-10mg until the desired effects are achieved. The gel capsules contain 25mg of CBD per pill. There is no harm in starting at 25mg CBD daily as you cannot overdose on CBD, nor are there any serious side effects. CBD provides sustained relief for several hours, many people find it provides relief for the whole day! The one thing to keep in mind with ingestible CBD products is the delayed onset time, it can take up to 90 minutes for the full effects of the tinctures or capsules to be felt.

For pain located in the skin, bones, muscle, ligaments, tendons, or myofascial tissue, we also recommend supplementing with a topical CBD salve, to penetrate deep beneath the skin layer to reduce inflammation and pain. Relief can be felt within 15 minutes and lasts several hours. Simply re-apply as necessary.

Managing acute flairups

In addition to the daily pain management program outlined above, many people find they still need a safe way to manage acute flairups. Whether it's caused by a recent injury, cold weather, or general aggravation, vaporizing CBD isolate is recommended to combat these acute pain flairups. The benefit of vaporizing CBD isolate is that the relief can be felt almost instantaneously. CBD isolate is 99% pure CBD and provides a wave of relief that can be felt throughout the whole body.

You can also ingest more CBD in the form of tinctures or pills to combat these flairups, just keep in mind that the onset time will be significantly longer than vaporizing. CBD topical salves can also be used to manage acute pain flairups.

https://keytocannabis.com/blogs/cann...ain-management
 
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Salvia: Wonder drug for chronic pain

Salvia is a psychedelic plant native to the northeastern Sierra Mazateca mountain region of Mexico where the native Mazatecs have used it for centuries as a healing and divining tool.

In 2005 I gained the diagnosis of New Daily Persistent Headaches. Simply put, I have a constant headache that varies from a light thrumming to a full blown migraine. Over the years I have seen too many doctors and neurologists. I have tried a number of different pain killers, anti-depressants, marijuana, acid, meditation, hypnosis, acupuncture, relaxation therapy, positive thinking, reflexology, naturopathy, and more to manage my chronic pain. It was only in 2013 I tried Salvia and discovered its potential for pain management.

Given my extensive history with neurology, and my particular knowledge field as a student of chemical engineering, I decided to start a study of Salvia. I began microdosing with 50x Salvia in order to analyze the experience I had coming up.

The way Salvia grips my mind is like hitting a reset button. Most painkillers alleviate the feeling of chronic pain. Many other pills were designed to lower intensity and consistency of headaches and migraines. Salvia however completely removed me from the experience of pain. I also find it much more affordable and pleasurable than popping painkillers constantly.

Salvia is one the best things I have ever found. It took me from a world of constant pain to one of spiritual exploration. I've approached a number of neurologists and psychiatrists with regards to Salvia's potential as a healing medicine, especially in regards to chronic pain, but none were interested. So I venture to the internet in hopes that my experience can possible help those in need.

In summary, Salvia does wonders for my chronic pain. I have studied Salvia from a scientific point of view, and Salvia can act as a reset for the mind, bringing users to a calm space removed of all prior stress and pain.

Salvia is not for everyone. But I think that it is worth a try if done properly, as the potential benefits are great, especially for those with chronic illness as a natural alternative to pills. I smoke Salvia most days, and I don't intend to stop.

https://erowid.org/experiences/exp.php?ID=106369
 
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Does CBD oil need THC in it to work on pain?

For some patients, it does, for others no. I use almost pure CBD in the tincture I make..the cannabis I use, is 10% CBD and 0.01% THC. This works fine for me, though I use a regular medium THC percent cannabis for sleep assistance. IMHO, the best thing about using almost totally pure CBD is that I can take it all day and not be impaired while driving or performing my regular routine.

Most of we medical cannabis consumers have tried several options prior to finding out what works for us. Trial and error is, so far, the only way to determine your specific need for your specific pain level. Cannabis replaced 180mg of methadone 3 times a day for me, after several years of slowly lowering my daily methadone intake I also used CBD to help curtail the withdrawal symptoms.

Elle Hayes

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THC usually helps increase CBD’s pain relieving effects. A CBD:THC ratio of 20:1 is usually more effective than CBD alone. Some people may even prefer 10:1, 2:1, or 1:1 ratios. In my own experience, neurologically based pain requires less THC and a higher total dose, while systemic pain requires more THC and a relatively lower total dose. One theory states that the whole plant product - including CBD, THC and many other components - is greater than the sum of it’s parts.

Thomas Wrona

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You can also take a combination of the two, at a specific ratio. A lot of people use a 20:1 ratio of CBD/THC, lots of CBD, not much THC, and report greater pain relief. There are studies that show that THC can increase the effect of CBD for pain relief, but some people don’t like the "high" of THC.

Martin Walker

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I'm 45 and have my own landscape maintenance business. All summer I have been having knee pains, back pain and carpel tunnel symptoms in my hands. A few weeks ago I found out about CBD oil and started using it. Within 3 days every bit of pain disappeared. Each morning I will take about 20 drops (it tastes like peppermint) and it seems to keep all my aches and pains away. This particular CBD Oil is very potent, with 750 mg of CBD and less than .03 percent of THC. Different things work for different people but this one worked great for me. I believe in it so much I got involved and became a distributor aka affiliate. Here is my website if you would like to try this product or also join us in helping others get the product.

Shawn Cox

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I started taking 500 mg for pain but my pain was still present. I increased my dose to 1500 mg and that made all the difference. My pain is gone with the exception of a flare up, then I just increase my dose.

CBD Melanie

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For pain I would take a full spectrum CBD product. A full spectrum CBD product contains CBD and trace amounts of THC usually between 2–4%. I would say the ideal combo for pain management is high CBD, low THC. This combo has been proven to show strong results in the pain management sector.

Chad Waldman

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CBD works best when used in combination with at least some THC, to help it to bind to the receptor in your body, your cannabinoid receptors. You should try 2 drops of weak tincture under your tongue, and wait 30 minutes, you can continue to titrate to a dose that gets the results you want. If a weak tincture doesn’t work, you can go up in strengths.

Barb Kueber​
 
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How cannabis oil helped me get off painkillers

by Richart Holt | The Telegraph | 9 Oct 2017

In a backpacking hostel during a stag weekend 10 years ago, I fell asleep on a top bunk next to an open window. Of course, that now strikes me as a stupid thing to have done, but at the time I didn’t give it a thought. I was on a weekend away, not a health-and-safety awareness course. At some point during the night, I tried getting out of the bunk, but instead of turning left and using the ladder, I turned right and hopped straight out of the window.

I fell 24ft on to concrete. From a survival point of view, I was lucky to land on my feet. The downside was that some rather important sections of my legs did not come out of it so well.

My left heel was crushed, while over on the right, my tibia and fibula – the two long bones in the lower leg – detached from their couplings and shattered. The next few weeks involved operations, plates, screws and quite unimaginable levels of agony. At one point, I felt a kind of blinding calm, as though the pain had gone all the way up the scale and rung a bell at the top.

While those pain levels have never returned, over the years there have been generous helpings of it; my legs didn’t take too kindly to being smashed up and bolted back together, and they seem to enjoy reminding me of this. After trying many different ways of managing the pain, eight months ago I started taking cannabidiol, or CBD for short – a non-psychoactive compound found in both hemp and cannabis plants.

The effect on the pain has been profound. It comes as an oil that I put under my tongue whenever pain moves from a dull niggle to the kind that is difficult to ignore.

CBD influences the release and uptake of neurotransmitters such as dopamine and serotonin, leading to many potential therapeutic uses. Crucially, it does not contain any THC, the psychoactive component of cannabis; in other words, CBD does not get you high. Since last year, it has been legal to buy in the UK, after the government’s Medicines and Healthcare Products Regulatory Agency (MHPR) approved its use as a medicine under licence.

CBD oil has since been prescribed to an 11-year-old British boy suffering from epilepsy, in what is believed to be the first instance of a cannabis-derivative being prescribed on the NHS.

Last month, a cancer patient diagnosed 4 years ago with an incurable brain tumor and given just 6 months to live, ascribed her incredible recovery to turning to cannabis oil as a last resort.

While research into the medical benefits of CBD oil is in its infancy, it is certainly encouraging. Recent reports suggest it could be a more useful anti-inflammatory than ibuprofen.

“There has been some early scientific evidence that CBD can help with inflammation,” says Dr Henry Fisher, of drug policy thinktank Volteface. “There is also a lot of anecdotal evidence that it helps people who do contact sports, because of the tendency to get inflamed joints. Taking other anti-inflammatories like ibuprofen on a long-term basis – as many sportspeople do – is not a good idea because of potential damage to your liver.”

"It also has distinct advantages over opioid medicines,"
says Dr Fisher. “With CBD, there is no evidence of any long-term negative impact, and no likelihood of addiction. And, of course, there are no known cases of anybody overdosing on CBD.”

The comparison to prescription medicine is particularly pertinent. For several months after my accident, I took Oxycontin, a common opioid painkiller. It was very useful at that time because it gave me a warm fuzzy feeling, making everything seem okay. But after a while, I started waking up feeling groggy and crushed. So I decided to stop, and the withdrawal was horrendous. It was several days of indescribable misery, so bad that it made the pain from the injuries feel like a slightly over-zealous massage.

Getting off that heavy-duty medicine was key for my recovery. Because this kind of medication saps your energy, and the one thing you need to fight back to full fitness is energy. I spent months in a wheelchair, then on crutches, then finally I was able to start taking slow, painful steps on legs that had forgotten what their purpose was.

Everyone that uses it tells a similar story: they sleep better and feel less pain. While there are ongoing trials for CBD as a treatment for everything from multiple sclerosis to Parkinson’s disease, all I know is that for me it can make the difference being sitting on the sofa and being able to go training. I can now lift and carry my children without wincing.

CBD does not make the pain go away completely, but that is okay – a bit of pain is necessary, an alarm system to warn of imminent peril. But once the message has been received, it is nice to be able to turn the volume down a little bit.

https://www.telegraph.co.uk/health-...bis-extract-cbd-replace-ibuprofen-painkiller/
 
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Cannabis effective for treating Fibromyalgia

by Paul Armentano | 5 Mar 2018

Cannabis therapy mitigates symptoms of the chronic pain condition fibromyalgia and is associated with a reduction in the use of other prescription drugs, according to clinical data published online ahead of print in the Journal of Clinical Rheumatology. 3 to 6 million Americans suffer from fibromyalgia, which is often poorly controlled by standard pain medications.

Israeli investigators assessed the safety and efficacy of inhaled cannabis in a cohort of 26 patients with fibromyalgia. They reported that medical cannabis treatment “was associated with significant favorable outcomes in every item evaluated,” such as reductions in pain and increases in energy.

Most patients also reduced their use of conventional prescription drugs, such as opiates and benzodiazepines, during the trial period. Nearly half of the participants (46 percent) reduced their prescription drug intake by more than 50 percent during the study. Several patients were also able to return to work following the initiation of cannabis therapy.

Researchers concluded, “Medical cannabis treatment had a significant favorable effect on patients with fibromyalgia, with few adverse effects.”

Prior trials evaluating the use of either whole-plant cannabis or synthetic cannabinoids have similarly shown efficacy in patients with the disease. A summary of these prior studies is available here.

https://blog.norml.org/2018/03/05/study-cannabis-effective-at-treating-symptoms-of-fibromyalgia/
 
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CBD oil, a drug-free approach to treating chronic pain
*

by Dr. Robert Kornfeld | Huffington Post | 29 Aug 2017

We are now at the cutting edge of a new, safe, natural and supportive approach to treating chronic pain. And this approach is borne out of an understanding of a critically important natural physiologic system of the human body…the endocannabinoid system. The endocannabinoid system is a network of receptors in the human body that may well be the backbone of homeostasis. These receptors serve as a signaling system in the human body and are present in the central nervous system (CB1 receptors) as well as the peripheral nervous system and the immune system (CB2 receptors).

This system was discovered and named as a result of studying the effects of marijuana (derived from the plant cannabis sativa). The main psycho-active constituent of marijuana is THC. The reason marijuana has the effects it has is that the THC binds to this receptor network in the human body and induces feelings of exhilaration, relaxation and a feeling of well-being. These are the very same effects induced by endogenous neurotransmitters and endorphins – naturally occurring chemicals in the human body- that are the guardians of homeostasis. These naturally occurring chemicals can either keep our bodies running smoothly or intervene on behalf of health threats to guide the immune system to either repair and/or replace our cells (primary inflammation) or to protect the cells that cannot be repaired or replaced (chronic inflammation).

So we begin to see that instead of using drugs to block pain and inflammation, supporting and stimulating the endocannabinoid system can drive the human body to heal and repair. It’s important to note that both pain and inflammation are natural defense mechanisms. When we ingest drugs that block pain and inflammation, we are essentially blocking our defense mechanisms. To be clear, each night when we go to sleep, the pathway of primary inflammation works to detoxify our cells, repair injured cells and replace dead cells. This is a natural pathway that produces no pain and is essential for the maintenance of homeostasis. This is why sleep is so important. However, if the immune system is burdened by poor quality food, toxins from air and water, high levels of stress, lack of sleep and any number of other mechanisms causing immune deficiency, the pathway of primary inflammation will be overwhelmed and inefficient.

When we use drugs to block pain and inflammation, we wind up with a long list of potentially dangerous side effects. What has kept THC out of the realm of treating chronic pain is its association with inebriation and the fact that it is classified as an illegal drug. However, cannabis also contains high amounts of another naturally occurring compound known as CBD oil (CannaBiDiol). CBD has no psycho-active properties so there is no associated “high” with ingesting it. CBD is is not classified as a drug, it is legal in all 50 states, does not require a medical marijuana prescription and binds to our CB1 and CB2 receptors to drive a more potent primary inflammatory response similar to our naturally occurring neurotransmitters and endorphins. What is more remarkable is that it is not associated with any of the side-effects that are seen with drug therapy. Taken as directed it is incredibly safe. And if taken consistently, it can relieve pain and inflammation and reduce or eliminate the need for drug therapy. CBD is available to buy in capsules, as sub-lingual gels, tinctures and topical salves, but you can easily (and inexpensively) make high quality CBD oil yourself.

When we realize that CBD oil works with our bodies instead of against it, we understand why its safety profile is so high. It is my sincere hope that CBD oil will, in time, be accepted as part of the standard of care for pain and inflammation.

*From the article here :
https://www.huffingtonpost.com/entr...-treating-chronic_us_59a5927fe4b0b234aecad26c
 
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Can ketamine replace opioids for acute pain in emergency care?

Opioids are a mainstay in the management of acute pain, but due to their side effects, physicians are under increased pressure to be more selective in their prescription. A recent review investigated if ketamine for pain management is a viable alternative in the emergency department.

The most common symptom during visits to the emergency department is acute pain. Managing this pain is a major aspect of initial care in hospital settings and opioids are an effective and widely available treatment option. However, there is an increased push from physician research groups to reduce overall prescriptions of opioids in emergency care settings while improving health outcomes for patients.

Ketamine for pain management has been recognized as a possible alternative. An inhibitor of NMDA receptors in nerve cells, ketamine can create dissociative anaesthetic states with hallucinatory sensations at higher doses. In the emergency department, ketamine is often administered at sub-dissociative doses as a sedative during procedures and for intubated patients.

Comparing ketamine to opioids for pain management

A team of researchers in the United States recently completed a systematic review comparing the effect of low-dose ketamine to opioids for adult pain management in the emergency department. Their full report was published in Academic Emergency Medicine.

Studies were included in the systematic review if they were randomized controlled trials comparing intravenous low dose ketamine to opioids in emergency department settings. They excluded pediatric studies, studies that were not placebo-controlled, did not report pain scores or co-administered additional medications.

Due to stricter selection criteria compared to previous reviews on the subject, the literature search and study selection yielded three studies totaling 261 patients. After extracting and pooling the pain scores from the selected studies, ketamine was found to be comparable in effectiveness to opioids in the treatment of acute pain.

Ketamine is comparable to opioids without the respiratory effects

Adverse events were associated with ketamine administration and were mainly related to lower urinary tract symptoms, including increased urinary frequency as well as the possibility of renal failure. Opioids had side effects differing in nature, including nausea, vomiting, and respiratory depression. Ketamine administration may therefore be preferable to opioids, in elderly patients or patients with pulmonary disorders where opioid use can cause respiratory depression or failure.

Concerns regarding addiction

Concerns over addiction have been one of the driving forces to find alternatives to opioids, but according to the study authors there is little evidence linking addiction with acute administration of opioids in the emergency department. With chronic use, ketamine has the potential to lead to addiction as well.

This systematic review suggests that ketamine for pain management is a viable alternative to opioids for in the emergency department. Due to the risks of prescribing opioids in certain patient subgroups, the authors maintain that ketamine can provide comparable levels of pain relief while avoiding respiratory side effects.

https://www.medicalnewsbulletin.com/...ids-emergency/


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RCs closest to ketamine


MXE (3-MeO-2-Oxo-PCE) will be the RC closest to ketamine.

-fireflagknown (reddit)

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I prefer 2f-ket. It is shorter lasting but feels cleaner and closer to real ket. Duration is 2-3 hours.

-Mutagenic_pasta (reddit)

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Methoxmetamine (MXM) is probably the RC closest to ketamine. MXE is superior for me but not much like k.

-K8hudson1 (reddit)

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MXE and O-PCE are very similar, and my all time favorite drugs ever that have extreme anti-depressive qualities.

-RCluminati (reddit)

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Deschloroketamine (aka O-PCM, DXE, and DCK) is advertised as a ketamine replacement. It's much cheaper. I found it
to be about 2x more potent than K, and last about twice as long.

https://www.erowid.org/experiences/exp.php?ID=107008

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There is an RC chemical out called 2-FDCK / 2-fluorodeschloroketamine. I've been looking at that as a substitute [for pain].

-anon (BL)​
 
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Ketamine infusion therapy for Fibromyalgia and Rhumatoid Arthritis

by Jose Marques Lopes, PhD | Fibromyalgia News Today | 22 May 2018

Treatment with intravenous ketamine eased pain significantly in a patient with rheumatoid arthritis (RA) and fibromyalgia, a case report shows.

The report, Intravenous Ketamine Alleviates Pain in a Rheumatoid Arthritis Patient With Comorbid Fibromyalgia, was published in the journal The Journal of Medical Cases.

Patients with RA are at increased risk to develop fibromyalgia. Both disorders disproportionally affect women. RA may be treated with diverse types of medications that target pro-inflammatory cytokines - molecules released by immune cells - including analgesics, non-steroidal anti-inflammatories (NSAIDs), glucocorticoids, and disease-modifying therapies.

However, lack of response in some patients and medication-related problems warrant evaluation of alternative treatments.

Intravenous (IV) ketamine has been an FDA-approved medication for nearly 50 years. Ketamine blocks the NMDA (N-methyl-D-aspartate) receptor, which is key in neuronal communication and is involved in regulating pain signals in the brain and spinal cord. Excessive activation of this receptor may cause toxicity, leading to various pain disorders.

By blocking NMDA receptors, ketamine may correct this over-activation. However, ketamine?s therapeutic effects go well beyond its levels in the body, which leads scientists to speculate that it induces secondary changes that result in durable benefits.

A combination of analgesic, immunomodulatory and anti-inflammatory effects have been proposed for ketamine, which makes it promising for treating RA, according to the authors.

This report describes the case of a 49-year old woman with RA whose arthritis did not respond to conventional treatment options and resulted in permanent, extreme pain. She reported joint pain with stiffness in the morning in hands and shoulders, which limited finger and wrist movement and reduced her quality of life significantly.

The patient also had diffuse muscular pain and met diagnostic criteria for fibromyalgia.

Several treatment options, including physical therapy and conventional medications, "did not achieve adequate pain control for either condition, so I decided to use [IV] ketamine as an alternative therapeutic option," Ashraf Hanna, MD, the study?s lead author, said in a press release.

The patient started a 10-day IV ketamine infusion treatment for four hours per day. The initial dose was 428 mg, gradually increased to 1,063 mg.

She reported decreased pain after the first infusion session, and being almost pain-free after the last session. She also was no longer experiencing RA symptoms, including joint pain and morning stiffness.

Although he noted this is the first published report on the use of ketamine in RA, Hanna considered that "ketamine appears to possess unique immunomodulatory and analgesic properties that effectively reduce inflammation and reduce pain without the use of opioid/NSAID analgesics."

The authors cautioned that the findings are from only one patient and did not compare ketamine with placebo. However, "we are hopeful that future adequately powered and placebo-controlled clinical trials may confirm that ketamine is safe and effective for the treatment of autoimmune diseases such as RA," they wrote.

Unlike in the past, ketamine's effectiveness is now recognized by diverse insurance companies. "We hope to continue to add new Ketamine-compliant insurance companies in 2018," Hanna said.

"I have provided over 8,000 ketamine infusions and have seen so many incredible successes over the past 5 years. Some of my patients were unable to move a limb or walk, and now they have complete mobility and can walk unaided," Hanna said.

https://fibromyalgianewstoday.com/20...ra-study-says/
 
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